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Biotinidase deficiency, a rare metabolic disorder characterised by abnormal biotin metabolism, affects the biotin-dependent carboxylase functions. Primarily characterised by neurological and skin disorder, it may present with myriad features. Early recognition is important for preventing long-term morbidities. Here, we describe a case of a neonate presenting with seizures and a clinical picture suggestive of immunodeficiency. Multiple superficial abscesses along with septic arthritis of the left knee and left hip led to suspicion of primary immunodeficiency disorder. On evaluation, there was severe biotinidase deficiency. The neonate was supplemented with biotin, after which there were no further episodes of severe infection requiring hospitalisation, seizures or skin manifestation. This case report highlights the wide spectrum of clinical picture these disorders may present with and the low threshold for their evaluation and treatment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Holocarboxylase synthetase deficiency (HLCS deficiency, OMIM #253270) is an exceedingly rare metabolic disorder resulting in multiple carboxylase deficiencies owing to impaired biotin cycle. Clinical manifestations include severe metabolic acidosis, hyperammonemia, tachypnea, skin rash, alopecia, feeding problems, hypotonia, developmental delay, seizures, and, in severe cases, death., Methods and Results: An 8-day-old female neonate presented with severe lactic acidosis, necessitating sedation and mechanical ventilation. Despite receiving supportive care, no evident clinical improvement was observed, accompanied by the onset of generalized ichthyosis. Genetic analysis of actionable metabolic disorders revealed compound heterozygous variants of HLCS (NM_000411.8), specifically c.[710T>C (p.Leu237Pro)]; [1544G>A (p.Ser515Asn)], prompting the initiation of biotin mega-dose therapy (10 mg/day). Remarkably, dramatic clinical improvement in lactic acidosis was observed the day after initiating biotin administration, leading to the discontinuation of mechanical ventilation within 6 days. The patient remained in stable condition during follow-up, exhibiting normal growth and development along with consistently stable laboratory findings up to 18 months of age., Conclusion: Our case highlights the significance of early genetic testing in neonates with unexplained metabolic disorders to enable timely diagnosis and therapy initiation. Biotin therapy has demonstrated remarkable efficacy in improving the clinical condition of patients with HLCS deficiency, leading to favorable outcomes., (© 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

The sodium-dependent multivitamin transporter encoded by SLC5A6 is responsible for uptake of biotin, pantothenic acid, and α-lipoic acid. Thirteen individuals from eight families are reported with pathogenic biallelic SLC5A6 variants. Phenotype ranges from multisystem metabolic disorder to childhood-onset peripheral motor neuropathy. We report three additional affected individuals with biallelic SLC5A6 variants. In Family A, a male proband (AII:1) presenting in early childhood with gross motor regression, motor axonal neuropathy, recurrent cytopenia and infections, and failure to thrive was diagnosed at 12 years of age via genome sequencing (GS) with a paternal NM_021095.4:c.393+2T>C variant and a maternal c.1285A>G p.(Ser429Gly) variant. An uncle with recurrent cytopenia and peripheral neuropathy was subsequently found to have the same genotype. We also report an unrelated female with peripheral neuropathy homozygous for the c.1285A>G p.(Ser429Gly) recurrent variant identified in seven reported cases, including this study. RT-PCR studies on blood mRNA from AII:1 showed c.393+2T>C caused mis-splicing with all canonically spliced transcripts in AII:1 containing the c.1285A>G variant. SLC5A6 mRNA expression in AII:1 fibroblasts was ~50% of control levels, indicative of nonsense-mediated decay of mis-spliced transcripts. Biotin uptake studies on AII:1 fibroblasts, expressing the p.(Ser429Gly) variant, showed an ~90% reduction in uptake compared to controls. Targeted treatment of AII:1 with biotin, pantothenic acid, and lipoic acid resulted in clinical improvement. Health Economic analyses showed implementation of GS as an early investigation could have saved $ AUD 105,988 and shortened diagnostic odyssey and initiation of treatment by up to 7 years., (© 2024. The Author(s), under exclusive licence to European Society of Human Genetics.)

Biotinidase deficiency (BTD) is a treatable, inherited metabolic disorder commonly characterised by alopecia, dermatitis, seizures and developmental delay. It can also manifest as optic neuritis and myelitis; however, these are infrequently described in the literature. We report three cases who presented with quadriplegia and vision loss, initially managed as neuromyelitis optica spectrum disorder (NMOSD), based on neuroimaging findings. Two of them initially responded to immune therapy but relapsed after a few months, while one case showed no clinical improvement with immune therapy. The clinical presentation and neuroimaging findings in all three cases were consistent with NMOSD, leading to a delayed diagnosis of BTD. Antiaquaporin4 and antimyelin oligodendrocyte glycoprotein antibodies were negative in all patients. Urine organic acids reported raised markers of biotinidase or holocarboxylase synthase deficiency. Two of them had a dramatic response to biotin supplementation, showing significant improvement in motor function and vision., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

We report a case of a boy in his middle childhood who presented with inspiratory stridor and lactic acidosis and was subsequently diagnosed with partial biotinidase deficiency. Fibreoptic laryngoscope showed paradoxical vocal fold mobility.Partial biotidinase deficiency is an inherited disorder in which the body is unable to recycle the vitamin biotin. It may result in clinical consequences and can be easily treated with biotin but need a high index of suspicion to diagnose. The main symptoms include ataxia, seizures, hypotonia, psychomotor retardation, alopecia, skin rash, progressive deafness, optic atrophy and life-threatening episodes of metabolic acidosis. Laryngeal stridor is an uncommon presentation, but it is reversible in case of biotinidase deficiency. Invasive procedure like tracheostomy has not been shown to enhance outcomes., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background : Biotin-thiamine-responsive basal ganglia disease (BTBGD) is a rare, treatable autosomal recessive neurometabolic disorder. This condition eventually leads to severe disability and death if not treated correctly. The clinical features of BTBGD, especially those with unusual complications, are not widely known by neurologists or pediatricians. Case presentation : A 4-month-old male infant was admitted to the hospital with a history of cough for the past 7 days and convulsions of 6 h duration. Physical examination showed confusion, bilateral pupillary light reflex delays, hypertonia of limbs, and brisk tendon reflexes of the limbs. Brain magnetic resonance imaging (MRI) showed multiple abnormal signals in the bilateral basal ganglia, lobes, corpus callosum, brainstem, and brain atrophy. However, his condition continued to worsen. Computed tomography performed 3 months later showed severe subdural hematoma and effusion. Subsequently, he underwent puncture drainage; however, his condition did not improve postoperatively. Repeated MRIs showed increasing subdural hematoma and effusion, and brain atrophy. The patient was diagnosed with BTBGD following whole-genome sequencing, which identified a novel compound heterozygous mutation of SLC19A3 gene. He was treated with biotin and thiamine, and the symptoms gradually improved. Subsequent MRIs showed a decrease in the subdural hematoma and effusion and partial improvement in brain atrophy. Conclusion: To the best of our knowledge, this is the first reported case of BTBGD, complicated by severe subdural hematoma. These observations extend our understanding of the clinical features, neuroimaging spectrum, and gene mutation spectrum of BTBGD. The phenotypic spectrum and pathophysiology of BTBGD are not completely understood and need to be studied further.

Ethnopharmacological Relevance: Acute lung injury (ALI) ranks among the deadliest pulmonary diseases, significantly impacting mortality and morbidity. Presently, the primary treatment for ALI involves supportive therapy; however, its efficacy remains unsatisfactory. Strictosamide (STR), an indole alkaloid found in the Chinese herbal medicine Nauclea officinalis (Pierre ex Pit.) Merr. & Chun (Wutan), has been found to exhibit numerous pharmacological properties, particularly anti-inflammatory effects., Aim of the Study: This study aimes to systematically identify and validate the specific binding proteins targeted by STR and elucidate its anti-inflammatory mechanism in lipopolysaccharide (LPS)-induced ALI., Materials and Methods: Biotin chemical modification, protein microarray analysis and network pharmacology were conducted to screen for potential STR-binding proteins. The binding affinity was assessed through surface plasmon resonance (SPR), cellular thermal shift assay (CETSA) and molecular docking, and the anti-inflammatory mechanism of STR in ALI treatment was assessed through in vivo and in vitro experiments., Results: Biotin chemical modification, protein microarray and network pharmacology identified extracellular-signal-regulated kinase 2 (ERK2) as the most important binding proteins among 276 candidate STR-interacting proteins and nuclear factor-kappaB (NF-κB) pathway was one of the main inflammatory signal transduction pathways. Using SPR, CETSA, and molecular docking, we confirmed STR's affinity for ERK2. In vitro and in vivo experiments demonstrated that STR mitigated inflammation by targeting ERK2 to modulate the NF-κB signaling pathway in LPS-induced ALI., Conclusions: Our findings indicate that STR can inhibit the NF-κB signaling pathway to attenuate LPS-induced inflammation by targeting ERK2 and decreasing phosphorylation of ERK2, which could be a novel strategy for treating ALI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Biotinidase deficiency (BD) is an autosomal recessive inherited metabolic disorder which results from the inability of biotin-dependent carboxylase enzymes to function due to the release and absorption of biotin, leading to neurological and cutaneous findings. In the present study, evaluation of demographic characteristics, clinical findings, laboratory results, molecular genetic characteristics, and genotype-phenotype correlations of cases with BD. Two hundred forty-seven cases were included in the study who were admitted to the Department of Pediatric Metabolism of Ankara Bilkent City Hospital after being identified with potential BD through the Newborn Screening Program (NBS), during family screening or based on suspicious clinical findings, or following the detection of a pathogenic variant in a BTD genetic analysis during the period of October 2020 and February 2022. The medical files of the cases were reviewed retrospectively. An analysis of the admission routes of all cases to our clinic revealed 89.5% NBS, 5.7% family screening, and 4.9% suspicious clinical findings suggestive of BD. Complete enzyme deficiency was identified in 19.8%, partial enzyme deficiency in 55.1%, and heterogenous enzyme deficiency in 9.7%. The most common pathogenic variants were c.1270G > C (p.Asp424His), c.410G > A (p.Arg137His), and c.38_44delGCGCTGinsTCC (p.Cys13Phefs*36) in BTD gene. The c.1270G > C variant was most common in patients with cutaneous symptoms. The c.410G > A and c.38_44delGCGCTGinsTCC variants were more common in the patients with neurological symptoms. The mean activity level in patients with the c.1270G > C homozygous variant was statistically significantly higher than the mean activity level in the c.1270G > C compound heterozygous patients and the activity level of patients without the c.1270G > C variant. The mean activity level in c.410G > A homozygous patients was statistically significantly lower than the mean activity level of the c.410G > A compound heterozygous patients and the activity level of patients without the c.410G > A variant. In the course of our study, four new pathogenic variants were detected, namely: c.190G > A (p.Glu64Lys), c.249 + 5G > T, c.228delA (p.Val77*), and c.682A > G (p.Ile228Val).     Conclusions: The present study has determined the clinical and genetic spectrum of a large group of patients with BD in a single center. The frequent mutations in our study were similar to those reported in literature, and four novel variants were also described. What is Known: • Biotinidase deficiency is an autosomal recessive, treatable inborn error of metabolism. Two hundred ninety-four pathogenic variants in the BTD gene have been identified and the c.1270G > C variant is the most frequent BTD gene mutation in both Turkey and around the world. What is New: • Four new pathogenic variants (c.190G > A, p.Glu64Lys; c.249 + 5G > T; c.228delA, p.Val77*; and c.682A > G, p.Ile228Val) have been identified. It is believed that the c.38_44delGCGGCTGinsTCC variant is more commonly seen in individuals with ocular issues; however, further genotype-phenotype correlations are needed., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Biallelic pathogenic variants in SLC5A6 resulting in sodium-dependent multivitamin transporter (SMVT) defect have recently been described as a vitamin-responsive inborn error of metabolism mimicking biotinidase deficiency. To our knowledge, only 16 patients have been reported so far with various clinical phenotypes such as neuropathy and other neurologic impairments, gastro-intestinal dysfunction and failure to thrive, osteopenia, immunodeficiency, metabolic acidosis, hypoglycemia, and recently severe cardiac symptoms., Methods: We describe a case report of a 5-month-old girl presenting two recurrent episodes of metabolic decompensation and massive cardiac failure in the course of an infectious disease. We compare clinical, biological, and genetic findings of this patient to previous literature collected from Pubmed database (keywords: Sodium-dependent multivitamin transporter (SMVT), SMVT defect/disorder/deficiency, SLC5A6 gene/mutation)., Results: We highlight the life-threatening presentation of this disease, the stagnation of psychomotor development, the severe and persistent hypogammaglobulinemia, and additionally, the successful clinical response on early vitamin supplementation (biotin 15 mg a day and pantothenic acid 100 mg a day). Metabolic assessment showed a persistent increase of urinary 3-hydroxyisovaleric acid (3-HIA) as previously reported in this disease in literature., Conclusion: SMVT deficiency is a vitamin-responsive inborn error of metabolism that can lead to a wide range of symptoms. Increased and isolated excretion of urinary 3-hydroxyisovaleric acid may suggest, in the absence of markedly reduced biotinidase activity, a SMVT deficiency. Prompt supplementation with high doses of biotin and pantothenic acid should be initiated while awaiting results of SLC5A6 sequencing as this condition may be life-threatening., (© 2024 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Background: Biotinidase deficiency is caused by absent activity of the biotinidase, encoded by the biotinidase gene (BTD). Affected individuals cannot recycle the biotin, leading to heterogeneous symptoms that are primarily neurological and cutaneous. Early treatment with biotin supplementation can prevent irreversible neurological damage and is recommended for patients with profound deficiency, defined as enzyme activity <10% mean normal (MN). Molecular testing has been utilized along with biochemical analysis for diagnosis and management. In this study, our objective was to correlate biochemical phenotype/enzyme activity to BTD genotype in patients for whom both enzyme and molecular testing were performed at our lab, and to review how the correlations inform on variant severity., Methods: We analyzed results of biotinidase enzyme analysis and BTD gene sequencing in 407 patients where samples were submitted to our laboratory from 2008 to 2020., Results: We identified 84 BTD variants; the most common was c.1330G>C, and 19/84 were novel BTD variants. A total of 36 patients had enzyme activity <10% of MN and the most common variant found in this group was c.528G>T. No variant was reported in one patient in the profound deficiency group. The most common variant found in patients with enzyme activity more than 10% MN was c.1330G>C., Conclusions: Although enzyme activity alone may be adequate for diagnosing profound biotinidase deficiency, molecular testing is necessary for accurate carrier screening and in cases where the enzyme activity falls in the range where partial deficiency and carrier status cannot be discriminated., (© 2024 Quest Diagnostics. Pediatrics International published by John Wiley & Sons Australia, Ltd on behalf of Japan Pediatric Society.)

Patients with ulcerative colitis (UC) are reported to have changes in body structure, with negative impact on the course of disease. This study explored the effects of a standardized nutritional supplement containing five bacterial strains of at least five billion bacteria ( Bifidobacterium infantis , Bifidobacterium animalis , Lactobacillus bulgaricus , Lactobacillus helveticus , and Enterococcus faecium) , L-glutamine, and biotin on the body composition and quality of life of patients with UC. Ninety-three patients over 18 years of age with a confirmed diagnosis of UC, for whom body composition could be accurately determined, were included in this observational follow-up randomized study. These patients were split into two groups: UC-P (44 patients with dietary counselling and supplement with probiotics) and UC-NP (49 patients with dietary counselling, without supplement). Body composition was assessed using the multifrequency bioelectrical impedance device, and the quality of life related to UC was evaluated by applying the short inflammatory bowel disease questionnaire (SIBDQ). The results showed that the average value of muscular mass (MM) and sarcopenic index (SMI) significantly increased ( p = 0.043, respectively, p = 0.001) and a large fraction ( p = 0.001) of patients had their SMI levels normalized in the UC-P group compared with UC-NP group. The extracellular water to total body water ratio (ECW/TBW) also had significantly different mean values ( p = 0.022), favoring the UC-P group. By testing the differences between the average values of body composition parameters before and after treatment, we obtained significant results in body mass index (BMI) ( p = 0.046), fat free mass (FFM) ( p < 0.001), and ECW/TBW ratio ( p = 0.048). The SIBDQ total score increased significantly ( p < 0.001) in the UC-P group and was more strongly associated with changes in body parameters. Supplementation with probiotics associated with L-glutamine and biotin can improve body composition parameters, which in turn implies an increase in the overall quality of life of patients with UC.

A boy, aged 16 months, attended the hospital due to head and facial erythema for 15 months and vulva erythema for 10 months with aggravation for 5 days. The boy developed perioral and periocular erythema in the neonatal period and had erythema and papules with desquamation and erosion in the neck, armpit, and trigone of vulva in infancy. Blood gas analysis showed metabolic acidosis; the analysis of amino acid and acylcarnitine profiles for inherited metabolic diseases and the analysis of organic acid in urine suggested multiple carboxylase deficiency; genetic testing showed a homozygous mutation of c.1522C>T(p.R508W) in the HLCS gene. Finally the boy was diagnosed with holocarboxylase synthetase deficiency and achieved a good clinical outcome after oral biotin treatment. This article analyzes the clinical data of a child with holocarboxylase synthetase deficiency and summarizes the etiology, diagnosis, and treatment of this child, so as to provide ideas for clinicians to diagnose this rare disease.

Background: Biotinidase deficiency (BD) is an autosomal recessively inherited disorder that was first described in 1982. Forty years after its first description, we compiled available clinical data on BD with the aim of generating a more comprehensive picture of this condition., Methods: A systematic search strategy was performed in relevant databases without limits for publication date or languages. We screened 3966 records and included 144 articles reporting individuals with BD and their clinical presentation as well as the outcomes, when available., Results: This study included 1113 individuals with BD. More than half (51.5%) of these individuals were diagnosed by newborn screening, 43.3% in presence of clinical symptoms and 5.2% due to family screening. We grouped symptomatic individuals into four main clinical presentations: neonatal-onset (<1 month; 7.9%), early childhood-onset (<2 years; 59.2%), juvenile-onset (2-16 years; 25.1%) and adult-onset (>16 years; 7.7%). BD affected five main organ systems: nervous system (67.2%), skin (53.7%), eye (34.4%), auditory (26.9%) and respiratory system (17.8%). Involvement was mainly multisystemic (82.2%) of individuals, whereas isolated system presentation was seen in only 17.2% of individuals. When reported, metabolic acidosis was present in 42.4% of symptomatic individuals and characteristic abnormal organic acid metabolites were found in 57.1%. Biotin treatment led to clinical stability or improvement in 89.2% of individuals. 1.6% of reported individuals with BD died due to non-availability of treatment or late diagnosis., Conclusion: Newborn screening has had a major positive impact on the outcome of many individuals with BD. However, undiagnosed and non-treated BD remains a health concern. Given the risk of mortality or complications associated with late or missed diagnosis if newborn screening is not available, a trial of biotin should be considered in undiagnosed infants and adults exhibiting suspected clinical signs. Enzymatic activity and/or analysis of genetic variants can readily confirm the diagnosis of BD., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to describe the clinical, biochemical, and molecular characteristics of Chinese patients with holocarboxylase synthetase (HLCS) deficiency, and to investigate the mutation spectrum of HCLS deficiency as well as their potential correlation with phenotype., Methods: A total of 28 patients with HLCS deficiency were enrolled between 2006 and 2021. Clinical and laboratory data were reviewed retrospectively from medical records., Results: Among the 28 patients, six patients underwent newborn screening, of which only one was missed. Therefore, 23 patients were diagnosed because of disease onset. Among all the patients, 24 showed varying degrees of symptoms such as rash, vomiting, seizures, and drowsiness, while only four cases remained asymptomatic nowadays. The concentration of 3-hydroxyisovalerylcarnitine (C5-OH) in blood and pyruvate, 3-hydroxypropionate, methylcitric acid, 3-hydroxyvaleric acid, 3-methylcrotonylglycine in urine were increased greatly among affected individuals. After prompt supplement of biotin, both the clinical and biochemical symptoms were dramatically resolved and nearly all patients developed normal intelligence and physique on follow-up. DNA sequencing revealed 12 known and 6 novel variants in the HLCS gene of patients. Among them, the variant of c.1522C > T was the most common., Conclusions: Our findings expanded the spectrum of phenotypes and genotypes for HLCS deficiency in Chinese populations and suggested that with timely biotin therapy, patients with HLCS deficiency showed low mortality and optimistic prognosis. Newborn screening is crucial for early diagnosis, treatment, and long-term outcomes., (© 2023. The Author(s).)

Biotinidase deficiency is an autosomal recessive condition caused by pathogenic variants in the BTD gene. Resultant deficiency of free biotin leads to impaired activity of the enzyme carboxylase and related neurologic, dermatologic, and ocular symptoms. Many of these are reversible on treatment, but early recognition and commencement of biotin supplementation are critical. This practice is especially important in countries where routine neonatal screening for biotinidase deficiency is not performed. In this report comprising 14 patients from multiple centers, we demonstrate the MR imaging patterns of this disorder at various age groups. Knowledge of these patterns in the appropriate clinical context will help guide early diagnosis of this treatable metabolic disorder., (© 2023 by American Journal of Neuroradiology.)

Holocarboxylase synthetase deficiency (HSD) is a rare autosomal recessive disorder of biotin metabolism. Typical manifestations include irreversible metabolic disorders and erythroderma-like dermatitis. Most patients respond well to biotin supplementation. Psoriasis-like phenotype associated with this disease has been rarely reported in the literature and experiences with the use of biologics in patients with HSD are still lacking. We reported a rare case of recurrent psoriasis-like skin lesions in a 6-year-old child with HSD. The patient did not respond to initial therapy with high-dose oral biotin. Immunofluorescence staining showed an increased number of interleukin (IL)-17A+ cells in his skin lesions. Based on this finding, the patient was successfully treated with human anti-IL-17A monoclonal antibody (secukinumab). He did not report any side effects and remained healthy during the 2-year follow-up. We provide a comprehensive review of the reported cases of HSD with psoriasis-like dermatitis to date. The psoriasis-like phenotype of HSD is controversial in treatment and IL-17A inhibitor is an alternative therapeutic option., (© 2022 Japanese Dermatological Association.)

Automated immunoassays used to evaluate parathyroid function are vulnerable to different types of interference, which can affect clinical practices. This review provides a detailed overview of the six main types of interference known to affect the measurement of parathyroid hormone (PTH): heterophilic antibodies, biotin, PTH fragments, oxidized PTH (oxPTH), phosphorylated PTH, and some preanalytical factors. Because the prevalence of some of these conditions has been reported to approach 11.7%, and the frequency of testing for parathyroid function is important, the scale of the problem might be tremendous. Potential interference in parathyroid function testing should always be suspected whenever clinical or biochemical discrepancies arise. Their identification typically relies on additional laboratory tests, including method comparison, serial dilution, blocking reagent studies, affinity adsorption, and polyethylene glycol precipitation. Moreover, some of these issues can be mitigated with the development of mass spectrometry. This review also evaluated the clinical impact of parathyroid interference on immunoassays, including misdiagnosis, inappropriate parathyroidectomy; and delay in receiving appropriate therapy. Hence, strong communication should be maintained between the clinician and laboratory to avoid such scenarios., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Crocin is one of the main components of Crocus sativus L. and can alleviate oxidative stress and inflammation in diabetic nephropathy (DN). However, the specific mechanism by which crocin treats DN still needs to be further elucidated., Method: In the present study, a mouse model of DN was first established to investigate the therapeutic effect of crocin on DN mice. Subsequently, non-targeted metabolomics techniques were used to analyze the mechanisms of action of crocin in the treatment of DN. The effects of crocin on CYP4A11/PPARγ and TGF-β/Smad pathway were also investigated., Result: Results showed that crocin exhibited significant therapeutic and anti-inflammatory, and anti-oxidative effects on DN mice. In addition, the non-targeted metabolomics results indicated that crocin treatment affected several metabolites in kidney. These metabolites were mainly associated with biotin metabolism, riboflavin metabolism, and arachidonic acid metabolism. Furthermore, crocin treatment upregulated the decreased levels of CYP4A11 and phosphorylated PPARγ, and reduced the increased levels of TGF-β1 and phosphorylated Smad2/3 in the kidneys of DN mice., Conclusion: In conclusion, our study validated the considerable therapeutic, anti-inflammatory, and antioxidative impacts of crocin on DN mice. The mechanism of crocin treatment may be related to the regulation of biotin riboflavin and arachidonic acid metabolism, the activation of CYP4A11/PPARγ pathway, and the inhibition of TGF-β/Smad pathway in the kidney., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Acne is a chronic inflammatory disease of the pilosebaceous unit resulting from different cofactors. The alteration of the skin microbiome has recently been revealed to play a role in acne pathogenesis. Concerns with side effects of available systemic treatment for acne resulted in a greater focus on topical therapies, such as topical azelaic acid which showed to be an effective and safe treatment option for acne. The aim of our study was to evaluate the efficacy of a new treatment protocol for acne based on an oral supplement composed of biotin and 3 strains of lactic ferments combined with a topical gel composed of azelaic acid, hydroxypinacolone retinoate, and α-hydroxy acids., Methods: An Italian single-center interventional study was performed enrolling patients suffering from mild-to-moderate-acne. Patients were treated with a supplement based on biotin and 3 strains of lactic ferments, combined with a topical gel product (azelaic-acid, hydroxypinacolone retinoate, and α-hydroxy acids). All enrolled patients were scheduled for a total of 2 visits, a baseline visit (V0) and a follow-up visit after 60 days of treatment (V1)., Results: A total of 30 patients were enrolled in the study. Between V0 (baseline) and V1 (60 days), there was a reduction of 37.4% in the GAGS Score, 40.7% in the SEBUTAPEtm Score, and 18% in the TEWL Score, and an increment of 44% in the T-Blue Test Score. No cases of serious AEs were reported in our experience., Conclusions: Our results confirmed the promising therapeutic role of a probiotic supplement associated with topical therapy in the treatment of mild to moderate acne.

In previous studies, we found that dynorphin exerts antiepileptic effect by activating the kappa opioid receptor (KOR). However, the role of neuronal autophagy in dynorphin/KOR-mediated antiepileptic is still unclear. This study aimed to investigate the molecular mechanism of dynorphin's antiepileptic effect by inhibiting autophagy and reducing neuronal apoptosis. Here, a pilocarpine-induced rat model of epilepsy was established and hippocampal neurons were treated with Mg 2+ -free exposed for epileptiform activity induction. The real-time polymerase chain reaction and Western blot analysis were used to evaluate messenger RNA and protein expression. The TdT-mediated dUTP-biotin nick end labeling staining and flow cytometry were used to analyze cell apoptosis in vivo and in vitro. Neuron cells viability was detected by Cell Counting Kit-8 assay. Immunofluorescent staining and green fluorescent protein-light chain 3 immunofluorescence were used to measure autophagy in vivo and in vitro. Results showed that overexpression of prodynorphin alleviated neuronal apoptosis, activated the mammalian target of rapamycin (mTOR) signaling pathway, and inhibited neuronal autophagy in epileptic rats. Dynorphin inhibited Mg 2+ -free-induced seizure-like neuron apoptosis, partially reversing the effect of Mg 2+ -free on the mTOR signaling pathway and seizure-like neuron autophagy. Further, using rapamycin, we found that dynorphin inhibited Mg 2+ -free-induced seizure-like neuron autophagy and apoptosis by activating the mTOR signaling pathway. In conclusion, dynorphin inhibits autophagy by activating the mTOR signaling pathway and has a protective effect on epilepsy acute seizure and epilepsy-induced brain injury., (© 2022 International Federation for Cell Biology.)

Glioblastoma, a common malignancy of the central nervous system, is the most destructive type of brain cancer. Clinical treatment remains a major challenge due to high infiltrative growth and the presence of the blood brain barrier (BBB). Therefore, advanced nanoplatforms that can efficiently cross the BBB and target brain tumours are highly desired. Compared with the targeting efficiency of single ligand nanoplatforms, dual targeting nanoplatforms may lead to better and controllable malignant cell selectivity. In this study, based on our previous research of branched ligands, we finally determined to use tri-branched glucose and two-branched biotin as targeting molecules, and in order to explore the synergetic-targeting capabilities and the mutual influence between the length of the two ligands, we designed three kinds of two-branched biotin ligands with a different linker and co-modified with the tri-branched glucose ligands on the surface of liposomes. The results of in vivo and in vitro experiments showed the (Glu 3 +Bio 2 )-2-Lip can exert the greatest synergistic targeting ability. The application of branched ligands, the dual-targeting design concept, and the exploration of the interaction between the chain lengths of the two ligands have brought new ideas and new methods for the targeted therapy of glioma.

Background: Biotin-thiamine-responsive basal ganglia disease (BTBGD) is a treatable neurometabolic disease caused by variants in SLC19A3. Typical imaging features include symmetrical involvement of the caudate nuclei and putamina., Objective: The study sought to explore classical BTBGD without caudate nucleus involvement, to highlight the importance of recognizing this new pattern early in the disease., Methods: Individuals with genetically confirmed BTBGD who harbored the same homozygous variant: NM&#95;025243.4 (SLC19A3): c.1264A > G (p.Thr422Ala) and had atypical neuroimaging were recruited., Results: Nine patients with BTBGD had atypical neuroimaging findings on the first MRI scan. The median age at symptom onset was 3 years. All patients presented with classical clinical features of subacute encephalopathy, dystonia, ataxia, and seizures. During the acute crisis, MRI revealed bilateral and symmetric involvement of the putamina in all patients; one showed small caudate nuclei involvement. In addition, the thalami, cerebellum, and brain stem were involved in six patients, seven patients, and three patients, respectively. Treatment included a combination of high doses of thiamine and biotin. One patient died; he did not receive any vitamin supplementation. Two patients who were treated late had severe neurological sequelae, including generalized dystonia and quadriplegia. Six patients treated early had good outcomes with minimal sequelae, including mild dystonia and dysarthria. Two patients showed the classical chronic atrophic and necrotic changes already described., Conclusion: The early atypical neuroimaging pattern of BTBGD described here, particularly the lack of caudate nucleus involvement, should not dissuade the clinician and radiologist from considering a diagnosis of BTBGD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Renal fibrosis is an unavoidable end result of all forms of progressive chronic kidney diseases (CKD). Discovery of efficacious drugs against renal fibrosis is in crucial need. In a preliminary study we found that a derivative of artemisinin, dihydroartemisinin (DHA), exerted strong renoprotection, and reversed renal fibrosis in adenine-induced CKD mouse model. In this study we investigated the anti-fibrotic mechanisms of DHA, particularly its specific target in renal cells. Renal fibrosis was induced in mice by unilateral ureteral obstruction (UUO) or oral administration of adenine (80 mg · kg -1 ), the mice received DHA (30 mg · kg -1  · d -1 , i.g.) for 14 or 21 days, respectively. We showed that DHA administration markedly attenuated the inflammation and fibrotic responses in the kidneys and significantly improved the renal function in both the renal fibrosis mouse models. In adenine-treated mice, DHA was more effective than 5-azacytidine against renal fibrosis. The anti-fibrotic effects of DHA were also observed in TGF-β1-treated HK-2 cells. In order to determine the target protein of DHA, we conducted pull-down technology coupled with shotgun proteomics using a small-molecule probe based on the structure of DHA (biotin-DHA). As a results, DNA methyltransferase 1 (DNMT1) was identified as the anti-fibrotic target of DHA in 3 different types of renal cell lines (HK-2, HEK293 and 3T3). We demonstrated that DHA directly bound to Asn 1529 and Thr 1528 of DNMT1 with a Kd value of 8.18 μM. In primary mouse renal tubular cells, we showed that DHA (10 μM) promoted DNMT1 degradation via the ubiquitin-proteasome pathway. DHA-reduced DNMT1 expression effectively reversed Klotho promoter hypermethylation, which led to the reversal of Klotho protein loss in the kidney of UUO mice. This subsequently resulted in inhibition of the Wnt/β-catenin and TGF-β/Smad signaling pathways and consequently conferred renoprotection in the animals. Knockdown of Klotho abolished the renoprotective effect of DHA in UUO mice. Our study reveals a novel pharmacological activity for DHA, i.e., renoprotection. DHA exhibits this effect by targeting DNMT1 to reverse Klotho repression. This study provides an evidence for the possible clinical application of DHA in the treatment of renal fibrosis., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

There continues to be questions and misconceptions about the administration of the vitamin, biotin, to children with the inherited biotin-responsive disorder, especially infants. Therefore, this commentary is intended to address the issues of biotin administration for healthcare workers, parents of children with the biotin-responsive disorders and the individuals with the disorders., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Combination therapy with biotin and dexpanthenol is a well-known practice in preventing and treating hair loss, however, it is not well studied. In this study, we compared the efficacy of the 6-week treatment with two brands of biotin and dexpanthenol for the treatment of diffuse hair loss. Fifty eligible patients with diffused pattern hair loss, (41 women and 9 men) were randomized in a 1:1 ratio to receive either 6 weekly injections of dexpanthenol ampoule 250 mg/2 ml and biotin ampoule 5 mg/1 ml, manufactured by Pars Behvarzan or Bayer Company. Combing test, Standard scalp photography and trichoscan assessment were performed before the first treatment session and one and 8 weeks after the last one. Patients' satisfaction and drug adverse reactions were also recorded. One and eight weeks after the last treatment session, hair fall count and total hair density significantly improved in both groups (p-value <0.01 for hair fall count and 0.04 and 0.02, for hair density in Pars and Bayer groups, respectively). There was no significant difference between the two groups in any other trichoscan parameter, except for improvement in terminal/vellus hair ratio in the Bayer group in both follow up visits, compared to the Pars group (p-value = 0.02 and 0.033 for weeks one and eight). Six-week treatment with both brands of biotin and dexpanthenol was effective and safe in people with diffused pattern hair loss., (© 2022 Wiley Periodicals LLC.)

This study aimed to determine the clinical spectrum and biochemical findings on urine organic acids (UOA) in Biotin-responsive multiple carboxylase deficiency (MCD) patients presenting to the biochemical genetics laboratory (BGL). Patients reported as MCD, from January 2013-December 2020 were included. The UOA was analysed by gas chromatography mass spectrometer. Demographic, clinical, and biochemical details were extracted from the BGL history form. Two hundred and two patients were reported to have biotin responsive MCD with 111(55%) males and a median (Q3-Q1) age of 7 months (13-4). Of these 71.7% (n=145) patients presented in infantile period. Parental consanguinity was observed in 80% (n=161) and another 32.6% (n=66) cases grandparents were cousins. The main presenting features were seizures, developmental delay, and lethargy. The common peaks were determined on UOA 3OHIVA, MC and MCC. MCD is not rare in Pakistani population; it is recommended to include this disorder in newborn screening programs. Key Words: Biotin responsive multiple carboxylase deficiency, Organic acids, Amino acids, Pakistan, Inborn errors of metabolism.

Deficiency of the biotinidase (BTD) enzyme is an inborn error of biotin metabolism caused by biallelic pathogenic variants in the BTD gene. There are two forms, partial and profound BTD deficiency, which both can be successfully treated with pharmacological doses of biotin, justifying the inclusion of this disorder in the newborn screening in numerous countries. We investigated the BTD deficiency cohort (N = 87) in our metabolic center, as it was detected upon newborn screening since 2005, and aimed to better understand the long-term course of BTD enzyme activity and how it may relate to the patients' genetic background. We observed that individuals with partial BTD deficiency display an elevation of BTD enzyme activity with increasing age in 48% of cases-a recovery which allowed adjustment or stop of biotin supplementation in 20% of all individuals. In addition, we were able to recruit 56 patients (64%) for genetic testing, revealing 19 different variants (2 novel), and constituting 22 different genotypes. Genotype-phenotype correlations revealed that the most abundant allele in our cohort p.(Asp444His) was also the most common variant in patients displaying recovery of BTD enzyme activity. Based on our results, we recommend to retest all patients with partial BTD deficiency at the age of 5 years, as this may result in an impact on therapy. Moreover, genetic testing of BTD deficient individuals can allow prediction of the severity of BTD deficiency and of the likelihood of BTD enzyme activity recovery with age., (© 2022 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

A new composite film from chitosan (CS) and biotin (BIO) was developed to enhance burn wound healing. The film was prepared by electrostatic interaction between CS and BIO. Four different ratios of CS to BIO v/v (4:1, 3:2, 2:3, and 1:4) were prepared. The films were comprehensively characterized using FTIR, DSC, and AFM. The in-vitro release studies showed that the most promising formula with the highest release behavior was CS to BIO 1: 4. The ex vivo adhesion times were reported as 0.50 ± 0.30 min for CS film compared to 6.2 ± 0.30, 8.4 ± 0.40, 11.2 ± 0.50, and 13.83 ± 1.04 min for CS to BIO films v/v (1:4, 2:3, 3:2 and 4:1), respectively. Most importantly, the skin healing activities of CS/BIO film in the excision wound model in mice and skin burn model in rats showed faster rates of healing compared to CS and placebo. Furthermore, skin stretching and burn wound contraction behavior treated with CS/BIO were higher than that of CS treated skin. In conclusion, the results obtained revealed that CS/BIO films possessed superior burn wound healing activity compared to CS.

Sodium-dependent multivitamin transporter (SMVT) deficiency is a recently described multivitamin-responsive inherited metabolic disorder (IMD) of which the phenotypic spectrum and response to treatment remains to be elucidated. So far, four pediatric patients have been described in three case reports with symptoms ranging from severe neurodevelopmental delay to feeding problems and failure to thrive, who demonstrated significant improvement after initiation of enhancement of targeted multivitamin treatment (biotin, pantothenic acid, and lipoic acid). We describe a fifth case of a patient presenting at the relatively mild end of the phenotypic spectrum with failure to thrive, frequent vomiting and metabolic acidosis with hypoglycemia, and mild osteopenia, who was diagnosed with SMVT deficiency due to compound heterozygous variants in SLC5A6 Additional genetic testing of variants of unknown significance (VUSs) as well as the clinical improvement in all aspects of the patient's disease upon initiation of treatment with biotin and pantothenic acid (plus lipoate as antioxidant) aided in the confirmation of this diagnosis. This case report aims to enhance recognition of the broad phenotypic spectrum of SMVT deficiency due to SLC5A6 mutations and discusses the different treatment strategies. It demonstrates how combining biochemical and genetic testing with the evaluation of (early) treatment response (i.e., using a "diagnostic therapeuticum") can influence confirmation of pathogenicity of genomic variants., (© 2022 Hauth et al.; Published by Cold Spring Harbor Laboratory Press.)

Magnesium biotinate (MgB) is a novel biotin complex with superior absorption and anti-inflammatory effects in the brain than D-Biotin. This study aimed to investigate the impact of different doses of MgB on social behavior deficits, learning and memory alteration, and inflammatory markers in propionic acid (PPA)-exposed rats. In this case, 35 Wistar rats (3 weeks old) were distributed into five groups: 1, Control; 2, PPA treated group; 3, PPA+MgBI (10 mg, HED); 4, PPA+MgBII (100 mg, HED); 5, PPA+MgBIII (500 mg, HED). PPA was given subcutaneously at 500 mg/kg/day for five days, followed by MgB for two weeks. PPA-exposed rats showed poor sociability and a high level of anxiety-like behaviors and cognitive impairments (p < 0.001). In a dose-dependent manner, behavioral and learning-memory disorders were significantly improved by MgB supplementation (p < 0.05). PPA decreased both the numbers and the sizes of Purkinje cells in the cerebellum. However, MgB administration increased the sizes and the densities of Purkinje cells. MgB improved the brain and serum Mg, biotin, serotonin, and dopamine concentrations, as well as antioxidant enzymes (CAT, SOD, GPx, and GSH) (p < 0.05). In addition, MgB treatment significantly regulated the neurotoxicity-related cytokines and neurotransmission-related markers. For instance, MgB significantly decreased the expression level of TNF-α, IL-6, IL-17, CCL-3, CCL-5, and CXCL-16 in the brain, compared to the control group (p < 0.05). These data demonstrate that MgB may ameliorate dysfunctions in social behavior, learning and memory and reduce the oxidative stress and inflammation indexes of the brain in a rat model.

Background and Aims: Biotin-thiamine-responsive basal ganglia disease (BTBGD) is an autosomal recessive disorder due to mutations in the SLC19A3-gene, typically seen in early childhood., Materials and Methods: We report a 49-year-old lady presenting with rapidly progressive cognitive impairment, seizures, hypersomnolence, ataxia, and generalized dystonia of 3 weeks duration. The magnetic resonance imaging (MRI) of the brain revealed T2-hyperintensities in the basal ganglia, thalamus, cortical, subcortical regions with striatal necrosis suggestive of BTBGD that was confirmed by genetic analysis. She was treated with thiamine and biotin following which there was significant clinical and MRI improvement., Conclusions: BTBGD requires a high index of suspicion in any patient presenting with unexplained rapidly progressive dementia. High doses of biotin and thiamine are the mainstay of the treatment to achieve a favorable outcome., Competing Interests: None

Multiple carboxylase deficiency (MCD) includes autosomal recessive holocarboxylase synthetase (HLCS) deficiency and biotinidase (BTD) deficiency, which are caused by and gene mutations respectively. Neonatal screening for HLCS deficiency is based on 3-hydroxyisovaleryl carnitine in dry blood filter paper, and BTD deficiency is based on BTD activity determination. HLCS deficiency and BTD deficiency are characterized by neurocutaneous syndrome and organic aciduria, however, they are different in onset age, neurological symptoms and metabolic decompensation, which needed to be differentiated from acquired biotin deficiency or other genetic metabolic diseases. The diagnosis of the disease requires a combination of biochemical characteristics of hematuria, enzyme activity determination and genetic test. Routine biotin doses are effective for most MCD patients. This consensus is intended to benefit early screening and diagnosis of MCD.

Biotin is an important cofactor in several metabolic pathways in humans. Biotin deficiencies are quite uncommon and there is limited data to support recommending it to treat hair, skin, and nail conditions. A 2017 FDA safety alert warned that biotin can interfere with laboratory testing resulting in incorrect diagnoses and even death. Therefore, our study objectives were to assess biotin recommendation practices and survey physician knowledge of biotin interference in routine laboratory tests. In a national survey of 149 physicians, we found that 43.9% of physicians prescribe biotin, primarily for hair and nail disorders, and 39.5% recommended other biotin-containing supplements. Most physicians answered correctly that there are no randomized studies that biotin improves dermatological conditions, and that biotin interferes with thyroid and troponin testing. Few knew of interference with b-HCG, Hepatitis serology, HIV serology and Vitamin D levels, and 19.5% were unaware of any interference. Almost half of physicians did not ask patients to discontinue biotin prior to laboratory testing. Our study shows that physicians continue to prescribe biotin despite knowledge gaps about laboratory interference, and highlights the need for increasing physician awareness of risks and benefits of recommending biotin to treat skin, hair, and nail conditions.

Skp1-Cul1-F-box protein (SCF) ubiquitin E3 ligases play important roles in cancer development and serve as a promising therapeutic target in cancer therapy. Brusatol (Bru), a known Nrf2 inhibitor, holds promise for treating a wide range of tumors; however, the direct targets of Bru and its anticancer mode of action remain unclear. In our study, 793 Bru-binding candidate proteins were identified by using a biotin-brusatol conjugate (Bio-Bru) followed by streptavidin-affinity pull down-based mass spectrometry. We found that Bru can directly bind to Skp1 and disrupt the interactions of Skp1 with the F-box protein Skp2, leading to the inhibition of the Skp2-SCF E3 ligase. Bru inhibited both proliferation and migration via promoting the accumulation of the substrates p27 and E-cadherin; Skp1 overexpression attenuated while Skp1 knockdown enhanced these effects of Bru in non-small cell lung cancer (NSCLC) cells. Moreover, Bru binding to Skp1 also inhibited the β-TRCP-SCF E3 ligase. In both subcutaneous and orthotopic NSCLC xenografts, Bru significantly inhibited the growth and metastasis of NSCLC through targeting SCF complex and upregulating p27 and E-cadherin protein levels. These data demonstrate that Bru is a Skp1-targeting agent that may have therapeutic potentials in lung cancer., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Biotin may activate the acetyl-CoA-, 3-methylcrotonyl-CoA-, propionyl-CoA-, and pyruvate carboxylases to increase myelin repair and/or synthesis, and may enhance the production of adenosine triphosphate (ATP), which may be essential to prevent neurodegeneration. The purpose of this review was to determine the effectiveness and safety of high-dose biotin (HDB) in multiple sclerosis via a systematic review of randomized controlled trials., Methods: We searched the following electronic databases for relevant articles: MEDLINE, CENTRAL, EMBASE, Scopus, and ClinicalTrials.gov website until April 2021. We considered randomized clinical trials (RCTs) that involved adult patients diagnosed with any phenotype of multiple sclerosis that conforms with the McDonald 2010/2017 criteria or the Lublin 2014 criteria. We included studies employing high-dose biotin or "MD1003" administered orally for at least 300 mg/day and given for at least three months. The methodological quality assessment of the included studies was done using the Cochrane Risk of Bias (RoB) tool. The GRADE approach was used to assess the certainty of evidence [COE]., Results: Out of 366 records identified, three RCTs involving 889 individuals diagnosed with MS (830 participants had progressive MS (PMS); 59 had RRMS) were pooled for analyses. The overall female:male ratio was 1.16:1. All included trials used HDB as an adjunctive treatment. The risks of bias in the three studies were low across the domains. At 12 to 15 months, there is insufficient evidence that the HDB and placebo arms differed in terms of composite improvement of MS-related disability (relative risk (RR) 2.87; 95% CI 0.29-28.40; 2 trials; 796 participants; I 2  = 66%) [low COE], improvement in expanded disability status scale (IEDSS) (RR 2.27; 95% CI 0.25-20.98; 2 trials; 796 participants; I 2  = 63%) [low COE], and both IEDSS and improvement in 25-foot walk time (ITW25) (IEDSS-ITW25) (RR 0.58; 95% CI 0.17-2.00; 2 trials; 796 participants; I 2  = 13%) [moderate COE] among patients with PMS. Pooled data for ITW25 at 12 to 15 months yielded statistical significance (RR 2.06; 95% CI 1.04-4.09; 2 trials; 796 participants; I 2  = 0%) [moderate COE] favoring HDB among patients with PMS. At 12 to 15 months, no significant differences were found in terms of mean change in EDSS (MD -0.06; 95% CI -0.14-0.02; 2 studies; 796 participants; 889 participants; I 2  = 68%) among patients with PMS. Synthesized data on incidence of any AEs (RR 0.98; 95% CI 0.92-1.04; 3 trials; I 2  = 0%) [high COE] and any serious AEs (RR 0.98; 95% CI 0.77-1.24; 3 trials; 889 participants; I 2  = 0%) [moderate COE] were not significantly different between HDB and placebo groups. Out of 662 pooled patients in the HDB group, 31 patients (4.7%) were found to have laboratory test interference compared to zero event in the pooled placebo group [high COE]., Conclusions: A moderate certainty of evidence suggests a potential benefit in favor of HDB administered for 12 to 15 months in terms of ITW25 in patients with PMS. However, an important trade-off of this benefit is the high certainty of evidence suggesting an increased incidence of laboratory test interference when HDB is taken., (Copyright © 2021. Published by Elsevier B.V.)

Dietary supplements are commonly recommended by dermatologists in the treatment of skin, hair, and nail disorders. This review of oral over-the-counter supplement use in dermatology summarizes current evidence for the use of zinc, biotin, vitamin D, nicotinamide, and Polypodium in the management of common dermatologic disorders. Evidence for the safety and efficacy of these supplements is limited. Very few large-scale randomized controlled trials exist for these over-the-counter supplements, particularly biotin and Polypodium. The lack of standardized dosing and standardized outcome measures makes comparison across existing studies challenging, and the lack of adverse events reporting in the majority of studies limits analysis of supplement safety. The most promising evidence exists for the use of nicotinamide in preventing nonmelanoma skin cancers. There is some evidence for the role of vitamin D in decreasing melanoma risk and progression in some individuals and for the photoprotective role of Polypodium, although additional high-quality studies are needed to determine appropriate dosing. Current evidence is insufficient to recommend the use of biotin or zinc supplements in dermatology. Large-scale randomized controlled trials investigating safety and efficacy are needed before widespread incorporation of these oral supplements into the general practice of dermatology., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Aim: In this study, we aimed to determine the incidence of hair loss in patients who underwent laparoscopic sleeve gastrectomy (LSG), and to observe whether use of Biotin has an impact on hair loss. Methods: This study included 156 female patients who underwent LSG for obesity and completed a 1-year follow-up. All patients with vitamin deficiency were screened in the pre- and postoperative period. Hair loss was defined as the subjective perception of the women of losing a higher amount of hair when compared with normal situation. Results: Hair loss was observed in 72% of the patients after LSG ( n  = 112). Seventy-nine percent of the patients reported hair loss between the third and fourth-month interval, and continued for an average of 5.5 ± 2.6 months. Permanent alopecia was not observed in any of the patients. Patients who experienced hair loss and Biotin deficiency after LSG were prescribed 1000 mcg/day of Biotin for 3 months. Of these 22 patients; only 5 (23%) patients reported a remarkable decline in hair loss. İn addition, 29 patients were found to take 1000 mcg/day of Biotin for average 2.5 months after onset of hair loss by their own initiative, despite optimal blood Biotin levels. Eleven (38%) patients reported a remarkable decline in hair loss. The effect of biotin use on hair loss in patients with and without biotin deficiency was compared. There was no significant difference ( P  = .2). Conclusion: Temporary hair loss after LSG is common. It was found that biotin supplementation used to prevent hair loss does provide low efficacy.

Background: High-dose pharmaceutical-grade biotin (MD1003) has positive effects on disability in progressive multiple sclerosis (PMS), but its mechanism of action remains unclear. The objective of our study was to quantify the effect of MD1003 in patients with PMS, using clinical response, plasma neurofilament light chain (pNfL) levels, and brain (BV) or cervical spinal cord volume (CSCV)., Materials and Methods: Forty-eight patients with PMS newly treated with MD1003 were followed during one year. Patients were assessed clinically using the Expanded Disability Status Scale (EDSS), the nine-hole peg test (9HPT), and the 25-foot walk time (25FWT). CSCV was quantified using CORDIAL software and BV using SIENA or SIENAX. We measured pNfL level using SIMOA at several time points. Bayesian linear and logistic regressions were used to evaluate potential prognostic factors., Results: Treatment response, defined as a significant decrease of EDSS, 25FWT, or 9HPT at 1 year, was observed in 13 patients (27%). A gain of volume was noted in 7/24 patients for brain and in 10/19 patients for cervical spinal cord. The strongest predictors of poor treatment response were a high pNfL level at MD1003 onset (OR 0.96; 95% CI [0.91; 1]), high age at MS onset (OR 0.95; 95% CI [0.89; 1.01]), and an increase in brain lesion load during MD1003 treatment (OR 0.81; 95% CI [0.55; 1.05])., Conclusions: MD1003 treatment was associated with clinical, BV, and CSCV improvement at 1 year. The correlation between the levels of pNfL at baseline, the age at multiple sclerosis onset, and a treatment response at M12 is consistent with a better effect in less disabled patients., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

High-dose biotin (HDB) is a therapy used in non-active progressive multiple sclerosis (PMS). Several reports have suggested that HDB treatment may be associated with an increased risk of relapse. We aimed to determine whether HDB increases the risk of clinical relapse in PMS and describe the characteristics of the patients who experience it. We conducted a French, multicenter, retrospective study, comparing a group of PMS patients treated with HDB to a matched control group. Poisson regression was applied to model the specific statistical distribution of the annualized relapse rate (ARR). A propensity score (PS), based on the inverse probability of treatment weighting (IPTW), was used to adjust for indication bias and included the following variables: gender, primary PMS or not, age, EDSS, time since the last relapse, and co-prescription of a DMT. Two thousand six hundred twenty-eight patients treated with HDB and 654 controls were analyzed with a follow-up of 17 ± 8 months. Among them, 148 validated relapses were observed in the group treated with biotin and 38 in the control group (p = 0.62). After adjustment based on the PS, the ARR was 0.044 ± 0.23 for the biotin-treated group and 0.028 ± 0.16 for the control group (p = 0.18). The more relapses there were before biotin, the higher the risk of relapse during treatment, independently from the use of HDB. While the number of relapses reported for patients with no previous inflammatory activity receiving biotin has gradually increased, the present retrospective study is adequately powered to exclude an elevated risk of relapse for patients with PMS treated with HDB.

Biotin (vitamin B7 or H) is found in milk, nuts, egg yolks, cereals, supplements, synthesized by intestinal bacteria, and is required for gluconeogenesis, fatty acid synthesis and amino acid catabolism.

Neonatal screening for biotinidase deficiency is still lacking in several countries worldwide, although this neurocutaneous disorder is treatable and preventable. Therefore, unscreened patients are diagnosed when symptomatic; treatment with Biotin is known to reverse cutaneous symptoms and improve neurological outcome. We describe a series of five symptomatic patients diagnosed with profound biotinidase deficiency and followed at a tertiary care center in Lebanon, for a variable period from 16 months to 11 years. Adjustment of Biotin therapy is correlated to clinical response and biochemical profile including 3-hydroxyisovalerylcarnitine on dried blood spots and urine organic acids. A previously unreported mutation is also reported in a patient who displayed an unusual outcome with reversible hearing loss on Biotin therapy. Clinical responsiveness to Biotin may be related to the underlying genetic mutation, although no clear genotype-phenotype correlation in biotinidase deficiency is proven. Furthermore, in the absence of systematic newborn screening for this disorder in several countries, identification of a reliable blood biomarker of Biotin responsiveness is warranted for better management of late diagnosed symptomatic patients., (Copyright © 2020 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objectives Holocarboxylase synthetase deficiency (HCSD) (OMIM #253270) is a rare inborn error of metabolism with an estimated annual incidence of 1 in 200,000 people. Typical manifestations of HCSD include eczema, alopecia, lactic acidosis and hyperammonemia. Diagnosis is made through genetic analysis. Case presentation Patient 1 was a 7-year-old girl with normal growth and development, presenting with severe hypoglycemia and metabolic acidosis. Her family reported that she was diagnosed as having ketotic hypoglycemia; she had five episodes of hypoglycemia and metabolic acidosis in past 4 years when her oral intake decreased during acute illness. Patient 2 was a 6-month-old female infant with normal growth and development, presenting with progressive generalized eczema and metabolic acidosis for the first time. We found that they both had hyperammonemia, hyperlactatemia, hyperketonemia, organic acids detected in urine and elevated C5OH acylcarnitine level by tandem mass spectrometry. HLCS gene analysis showed a homozygous pathogenic variant p.V363D in patient 1 and a pathogenic variant p.R508W compound with a novel splice site pathogenic variant c.2010-1G>A in patient 2. They have been on biotin treatment (10 mg/day for both of them) for more than 2 years and no more symptoms have occurred. Conclusions HCSD is a rare disease, and it can be fatal if severe metabolic acidosis occurs without timely management. Once the diagnosis is made, most of the patients with HCSD have good prognosis and normal life expectancy with biotin treatment.