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Objective: Infantile epileptic spasm syndrome (IESS), including West syndrome (WS) and infantile spasm (IS), causes a challenging prognosis, particularly when associated with metabolic etiologies., Methods: This study, conducted at a tertiary pediatric neurology center, explored the prevalence and clinical features of inborn errors of metabolism in 112 children with IESS over 10 years., Results: Most patients presented with seizures, primarily flexor spasms, and the median age at onset was 5 months. Comprehensive clinical evaluation and neuroimaging revealed structural-acquired causes as the most common etiology. Notably, inborn errors of metabolism were identified in 5.4 % of cases, with six distinct diagnoses including nonketotic hyperglycinemia, pyridoxine-dependent epilepsy, primary coenzyme Q10 deficiency 7, congenital disorder of glycosylation type IIM, 6-pyruvoyl tetrahydrobiopterin synthase deficiency, and argininosuccinate lyase deficiency. The prevalence of inborn errors of metabolism in this cohort was consistent with global variations reported in the literature. Genetic testing, including karyotype analysis and whole exome sequencing, was performed in a subset of cases with no clear diagnosis, revealing abnormalities in approximately 50 % of cases. Adrenocorticotropic hormone emerged as the most frequently prescribed antiseizure medication., Conclusion: This study provides insight into the diagnostic challenges associated with IESS and highlights the importance of metabolic investigations, especially in cases without a clear etiology. The findings emphasize the need for further genetic and metabolic studies to enhance prognostic accuracy and guide potential treatment options for children with IESS, particularly in populations with high rates of consanguinity., 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 © 2024 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Alpha mannosidosis is an autosomal recessive lysosomal storage disorder caused by biallelic pathogenic variants in the MAN2B1 gene. It manifests with clinical features, including intellectual disability, hearing impairment, coarse facial appearance, skeletal anomalies, immunodeficiency, central nervous system involvement, psychiatric comorbidities, corneal opacity, and hepatosplenomegaly. This multicenter study assesses the long-term outcomes of individuals diagnosed with alpha-mannosidosis, examining demographic, clinical, laboratory, and molecular characteristics., Method: Sixteen patients diagnosed with alpha-mannosidosis who presented to four pediatric metabolic units were included in the study. The patients' medical records were analyzed and data on demographics, clinical presentation and laboratory findings were recorded., Results: Of the 16 patients (6 females, 10 males) with alpha mannosidosis included in the study, the mean age at the time of diagnosis was 79.4 ± 56.1 (16-208) months, and the mean diagnosis delay time was 57.9 ± 51.9 (4-181) months. Hearing loss was the primary manifestation found in seven out of 16 patients (43.8%), followed by speech delay in 37.8%. On clinical follow-up, 87.5% of patients experienced recurrent infections, mainly in the upper respiratory tract, with 12 requiring the use of a hearing aid. Hepatomegaly was found in six out of 13 patients who received abdominal ultrasonography; two out of 12 patients who underwent echocardiography were found to have mitral valve prolapse (16.6%). Upon neurological evaluation, five patients displayed no neurological manifestation. Delayed language development was observed in nine (56.3%) patients, intellectual disability in eight (50%) patients, and hypertonicity was identified in one (6.3%) patient with the severe form of the disease. Homozygous c.2477C>A (p.Ser826Ter) and homozygous c.967G>A (p.Glu323Lys) novel variants were detected in four patients and one patient, respectively. The most common variant observed in the study was c.2477C>A (p.Ser826Ter)., Conclusion: The present study identified two novel MAN2B1 variants. An evaluation of the long-term outcome of alpha-mannosidosis, in which the early initiation of enzyme replacement therapy (ERT) may lead to a better clinical outcome, can permit a better analysis of the effect of ERT on the natural progression of the disease., 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 © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Asparagine synthetase deficiency (ASNSD) is a rare autosomal recessive neurometabolic disorder caused by homozygous or compound heterozygous mutations in the ASNS gene. Most of the patients have early-onset intractable seizures. A 7-year-old boy was first admitted to our clinic with intractable febrile and afebrile seizures that started when he was 6 months old. He had axial hypotonia with spastic quadriparesis, mild facial dysmorphism, and acquired microcephaly at 1 year-old. Metabolic tests showed a borderline-low serum asparagine level. The electroencephalogram demonstrated epileptic discharges with a high incidence of multifocal spike-wave activity. Brain MRI showed mild cerebral atrophy. His seizures continued despite combinations of multiple antiseizure agents. Whole-exome sequencing (WES) revealed a novel compound heterozygous missense variant of the ASNS gene, and the variants were confirmed by Sanger sequencing. He was started on a ketogenic diet at five years and six months of age. In the first month of the ketogenic diet, we observed that the frequency of seizures significantly decreased. He showed a remarkable improvement in seizures and milder improvement in cognitive skills. To our knowledge, our case is the first report describing significant improvement with a ketogenic diet in intractable seizures due to ASNSD., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Most IMDs are diagnosed in the neonatal period and have severe neurological findings. Neuroimaging plays an essential role in the diagnosis. We aim to investigate early cranial MRI findings of newborns suspected with IMDs to determine IMD-related neuroimaging patterns in the early infant period., Methods: The medical records of a total of 195 infants with suspected IMDs were screened, and 56 patients who underwent a cranial MRI within the first three months of life were included in the study. The 56 patients were categorized into those diagnosed (Group I) and those not diagnosed (Group II) with IMDs. The patient's clinical findings and radiological imaging reports were extracted to a database., Results: The most common IMDs were mitochondrial diseases, urea cycle disorders, and organic acidemias. In the cranial MRI evaluations, the T2-hyperintensity of white matter and the T2-hyperintensity of basal ganglia were higher in Group I. It was found that high lactate/lipid peaks on 1 H-MRS (10.68 times), T2-hyperintensity of white matter (5.75 times), and T2-hyperintensity of the basal ganglia (5.71 times) were more likely to be identified in Group I. Furthermore, no difference was noted between the groups in terms of the diffusion restriction of white matter, basal ganglia, cerebellum, and brainstem, and no statistically significant difference was noted in the T2-hyperintensity of the cerebellum and the brainstem., Conclusion: Early neuroimaging findings are essential in evaluations of IMDs, so familiarity with neuroimaging findings is essential for diagnosis, especially in countries that lack an expanded neonatal screening program., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Neuronal ceroid lipofuscinosis (CLN) 7 typically presents with motor and cognitive decline, seizures (myoclonus) and vision loss. Atypical manifestations such as, ataxia, Rett-like findings, microcephaly, personality disorders, extrapyramidal symptoms, stereotypical hand movements and autistic behaviors had been reported. A 7-year-old male patient referred with the diagnosis of sepsis and a medical history of afebrile seizure at the age of 3 years, and sleep problems and aggressive behavior at the age of 4 years. Dance-like movements were noted in his arms and legs. Laboratory tests identified elevated creatine kinase, and diffuse acanthocytes in a peripheral blood smear. A genetic analysis for chorea-acanthocytosis was conducted but no pathogenic variant was detected in the VPS13A gene. A homozygous deletion in the MFSD8 gene was detected with whole exome sequencing. Upon the initiation of treatment for the septic shock, the CK level regressed to normal value and the acanthocytes in the peripheral blood smear disappeared. Acanthocytosis and rhabdomyolysis were attributed to sepsis. This report suggest that CLN7 should be kept in mind in neurodegenerative findings with similar clinical findings and in the presence of choreo-athetotic movements., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest. Competing interests The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Status dystonicus is an underdiagnosed condition, probably due to heterogeneous etiology, presentation and course. Herein, we report the first case of CLN8 disease in the literature presenting with status dystonicus who responded well to pharmacological intervention., Case: A boy aged five years and three months presented with fever, loss of appetite, intermittent excessive dystonic contractions, opisthotonus with retrocollis, and irritability for three days. His developmental milestones were reported as normal up to the age of three years and six months. At this age, he developed seizures, ataxia, and vision problems. Deterioration in developmental milestones was observed from the age of four. Laboratory tests demonstrated leukocytosis, abnormal renal function, mild metabolic acidosis, elevated creatine kinase and transaminase levels. The brain magnetic resonance imaging demonstrated cerebral and cerebellar atrophy. Homozygous missense mutation of c.709G > A (p.G237R) in the CLN8 gene was revealed. With all these clinical and laboratory findings, he was diagnosed with status dystonicus associated with CLN8 disease. Antibiotherapy, anticonvulsant drugs, and intravenous hydration with alkaline fluids were initiated. Due to irregular breathing, dysphagia, and worsening of dystonic contractions, mechanical ventilation was performed, and baclofen, haloperidol, midazolam infusion and chloral hydrate were administered, respectively. Finally, serum creatine kinase levels decreased, and dystonic contractions improved on the 15th day of hospitalization., Conclusion: To the best of our knowledge, our case is the first report describing the status dystonicus in a patient with CLN8 disease. Our report suggested that neuronal ceroid lipofuscinoses should be kept in mind in the etiology of status dystonicus., 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 © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)