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Abstract Background Imerslund-Gräsbeck syndrome (IGS) is a rare autosomal recessive disorder characterized by megaloblastic anemia due to selective cobalamin malabsorption and benign proteinuria. IGS is caused by a disfunction of the cubam receptor, which mediates the reabsorption of cobalamin in the ileum and the reuptake of albumin in renal proximal tubules. Case presentation We describe the case of a 23-month-old-italian infant presenting with severe pancytopenia and failure to thrive in whom the diagnosis of IGS was made and vitamin B12 replacement therapy was resolutive. Genetic analysis (NGS with CNV analysis including 214 genes involved in bone marrow failure and anemia), showed the presence of two pathogenetic variants in the AMN gene (c-208–2 A > G and c.1006 + 34_1007-31del). These variants have been previously described in the literature, but their combination has never been reported. Conclusions Imerslund-Gräsbeck syndrome should be considered in the differential diagnosis of children with severe pancytopenia even in those without neurological involvement. This case emphasizes the importance of an early diagnosis and prompt treatment, to prevent irreversible neurological injury.

Background: Thrombotic microangiopathies (TMA) are characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and organ damage which occur in the setting of endothelial damage and platelet activation. Vitamin B12 (cobalamin) deficiency could lead to a picture that resembles TMA, termed metabolic mediated TMA (MM -TMA). Case Presentation: A 60-year-old female was brought to the hospital after she was found unresponsive. On presentation, she was pale, lethargic, tachycardic, and febrile. Laboratory investigations revealed normocytic anemia, thrombocytopenia, and elevated bilirubin. Blood smear revealed schistocytes and tear drop cells. Given the presence of hemolytic anemia, thrombocytopenia, acute renal failure, and altered mental status, a presumptive diagnosis of thrombotic thrombocytopenic purpura (TTP) was made with a PLASMIC score of 7 indicating high risk. She received plasma exchange, caplacizumab, and intravenous methylprednisolone. Given the patient’s low level of vitamin B12, she was initiated on intramuscular cyanocobalamin 1000 µg daily. The encephalopathy resolved and renal function improved. On day 6, ADAMTS13 activity was normal ruling out the diagnosis of TTP. Accordingly, plasmapheresis, steroids, and caplacizumab were discontinued. With continued aggressive B12 replacement, hemolysis resolved indicating severe vitamin B12 deficiency was the likely culprit of this patient’s microangiopathic hemolytic anemia. Conclusion: This case serves to highlight the variable presentation of vitamin B12 deficiency. Severe vitamin B12 deficiency can even mimic TTP. If patients have markers of hemolysis, a low vitamin B12 level, and low reticulocyte count we should consider vitamin B12 deficiency as a likely cause of microangiopathic hemolytic anemia as early detection allows for early initiation of appropriate management.

Introduction: Vitamin B12 is a water-soluble vitamin found primarily in animal-derived products such as red meat, dairy, and eggs. An essential substance for its absorption is the intrinsic factor, produced by the parietal cells of the stomach. After absorption in the distal ileum, cobalamin acts as a coenzyme in DNA synthesis and the metabolism of fatty acids and homocysteine. In addition to its well-known influence on the nervous system, it has been associated with gastrointestinal diseases according to numerous authors. Objective: The objective of this study is to gather and analyze literature regarding the associations between vitamin B12 deficiency and gastrointestinal diseases, including gastroesophageal reflux disease (GERD), gastritis, inflammatory bowel disease (IBD), small intestinal bacterial overgrowth (SIBO), and hepatitis C (HCV). Materials and Methods: A literature review was conducted using the PubMed database with the following search terms: vitamin B12, cobalamin, deficiency, gastrointestinal diseases, GERD, IBD, SIBO, HCV. Current Knowledge: Vitamin B12 deficiency can be caused by autoimmune factors, dietary insufficiencies, toxin exposure, and malabsorption disorders related to gastrointestinal diseases. Gastrointestinal conditions such as GERD and IBD can both lead to and be exacerbated by cobalamin deficiency. Furthermore, vitamin B12 deficiency may be worsened by prolonged use of proton pump inhibitors (PPIs) and Helicobacter pylori infection. Conclusions: An adequate amount of vitamin B12 is crucial for gastrointestinal health. Deficiency can significantly impact the course and symptoms of many gastrointestinal diseases. Therefore, monitoring and supplementation of vitamin B12 should be an integral part of managing patients with gastrointestinal conditions.

Abstract Imerslund-Gräsbeck syndrome (IGS) is a rare autosomal recessive disorder characterized by vitamin B12 malabsorption. Most patients present with non-specific symptoms attributed to vitamin B12 deficiency, and proteinuria. Patients may if untreated, develop severe neurocognitive manifestations. If recognized and treated with sufficient doses of vitamin B12, patients recover completely. We provide, for the first time, an overview of all previously reported cases of IGS. In addition, we provide a complete review of IGS and describe two new patients.

Abstract Background Low serum cobalamin concentrations have been associated with ileal malabsorption in dogs with chronic enteropathy. Increased serum methylmalonic acid (MMA) concentrations indicate cobalamin deficiency on a cellular level. Few studies have evaluated serum cobalamin concentrations or methylmalonic acid concentrations in juvenile dogs with parvoviral enteritis or nonparvoviral acute enteropathies. Objectives Evaluate serum cobalamin and methylmalonic acid concentrations in juvenile dogs (6 weeks to 10 months old) with parvoviral enteritis or nonparvoviral acute enteropathy. Animals Thirty‐one juvenile dogs with parvoviral enteritis, 29 dogs with nonparvoviral acute diarrhea (NPVAD), and 40 healthy juvenile control dogs. Methods Single‐center, prospective, observational, cross‐sectional study. Serum cobalamin and, when sufficient serum was available, MMA concentrations were measured. Results Most serum cobalamin concentrations were within the adult reference interval. Serum cobalamin concentrations in healthy dogs (median, 848 ng/L; range, 293‐1912 ng/L) were significantly higher than in dogs with parvoviral enteritis (P = .0002; median, 463 ng/L; range,

Abstract Background There is a paucity of studies reporting the presence of systemic symptoms and micronutrient deficiency in patients with chronic urticaria, and these data are lacking in a Canadian population. Objective To report the prevalence of gastrointestinal symptoms and vitamin B12 (cobalamin) deficiency in a Canadian patient population diagnosed with chronic urticaria. Methods A retrospective chart review of 100 adult patients with chronic urticaria was conducted. Demographic characteristics, medications, presence of gastrointestinal symptoms, and laboratory findings were abstracted from electronic medical records. Results Seventy percent of patients with chronic urticaria reported experiencing gastrointestinal symptoms. The most common symptom identified was gastroesophageal reflux (42%). Vitamin B12 (cobalamin) deficiency, defined as serum vitamin B12 level ≤ 250 pmol/L, was identified in 31.7% of the patients. Among those patients with urticaria and vitamin B12, 68% reported gastrointestinal symptoms. Conclusions This is the first study to provide data on the high prevalence of gastrointestinal symptoms and vitamin B12 (cobalamin) deficiency in a Canadian population diagnosed with chronic urticaria. Early recognition and management of systemic symptoms and micronutrient deficiency may lead to a more comprehensive approach to management of these patients. Trial registration Not applicable

Purpose Primary aldosteronism is one of the most frequent causes of secondary arterial hypertension, and whether primary aldosteronism is associated with masked hypertension is unknown. Materials and methods We describe a 64-year-old man with a history of hypothyroidism, recurring hypokalaemia, and normal home and office blood pressure values. Ambulatory blood pressure monitoring revealed masked hypertension with strikingly high systolic blood pressure variability and typical hypertension-mediated organ damage. Results The patient required gradual escalation of antihypertensive medication to four drugs. During the diagnostic process we identified primary aldosteronism, cobalamin deficiency, severe obstructive sleep apnoea, and low baroreflex sensitivity (1.63 ms/mmHg). Following unilateral adrenalectomy, cobalamin supplementation and continuous positive airway pressure, we observed a spectacular improvement in the patient’s blood pressure control, baroreflex sensitivity (4.82 ms/mmHg) and quality of life. Conclusions We report an unusual case of both masked arterial hypertension and primary aldosteronism. Elevated blood pressure values were masked in home and office measurements by coexisting hypotension which resulted most probably from deteriorated baroreflex sensitivity. Baroreflex sensitivity increased following treatment, including unilateral adrenalectomy. Hypertension can be masked by coexisting baroreceptor dysfunction which may derive from structural but also functional reversible changes.

Abstract Background Recent studies have shown similar efficacy of oral supplementation of cobalamin compared to injectable supplementation in dogs, but few prospective, randomized studies have been published. Objectives To evaluate efficacy of oral or injectable supplementation with cobalamin in normalizing serum cobalamin and methylmalonic acid (MMA) concentrations in dogs with hypocobalaminemia caused by either chronic enteropathy (CE) or exocrine pancreatic insufficiency (EPI). Animals Forty‐six client owned dogs with hypocobalaminemia. Methods Prospective randomized clinical trial. Dogs were divided into 2 groups (CE or EPI), and randomized to receive oral or injectable supplementation of cobalamin. Each dog had 3 visits and serum cobalamin and MMA concentrations were measured at each visit. Results In dogs with CE, serum cobalamin concentrations increased with oral (P = .02; median 149 [range 149‐231] to 733 [166‐1467] ng/L, median difference 552 [95% CI: 181‐899] ng/L) or injectable (P

Context: Cobalamin and folate are essential for the synthesis of nucleic acids and in the maintenance of myelin. They are required during the period of the rapid growth of infancy and childhood. Their deficiency may result in nutritional anemia and neurological manifestations. There is paucity of literature regarding the prevalence of cobalamin and folate deficiency among North Indian children aged 6–59 months. Aim: The aim of this study was to estimate the prevalence of serum cobalamin and folate deficiency among children aged 6–59 months, attending a secondary care hospital. Settings and Design: Children were recruited from pediatrics OPD of the sub-district hospital (SDH), Ballabgarh, Haryana, through systematic random sampling. Hemoglobin was measured by an automated analyzer. Serum cobalamin and serum folate were estimated using enhanced chemiluminescence based immunoassay. Results: A total of 420 children were recruited, of which 392 provided a blood specimen. Prevalence of cobalamin, folate deficiency, and anemia were 22.3% (95% CI: 18.3–26.7), 10.9% (95% CI: 8.2–14.6), and 81.9% (95% CI 77.7–85.4), respectively. The proportion of children with cobalamin deficiency who had anemia was 97.7% compared to 95.7% among those with no cobalamin deficiency (P = 0.396). Similarly, the proportion of children with folate deficiency who had anemia was 95.2% compared to 96.2% among those with no folate deficiency (P = 0.765). Conclusion: We found that almost one in five children aged 6–59 were deficient in cobalamin, and one in ten were deficient in folate.

Objective: Primary headaches are common and benign discomforts both in children and adolescents. However, they have a negative influence on the quality of life. This retrospective study aimed to determine the relationship between vitamin B12 results and primary headaches in Turkish children. Methods: Demographical features, headache types, laboratory results, including vitamin B12, were assessed retrospectively. Headache types were categorized as tension-type headache, migraine, and unclassified headache according to the International Classification of Headache Disorders-beta version (ICD-3 beta). Patients with seconder headaches, anemia, and macrocytosis were excluded. Results: The study group consisted of 133 (86 female, 47 male) patients with headache and a control group of 103 (57 female, 46 male) healthy children. There was no significant difference in terms of age and gender between groups (p>0.05). Vitamin B₁₂ levels in tension-type headache, migraine, and unclassified headache groups were significantly lower (p

Abstract Background Pyoderma gangrenosum (PG) is an uncommon, idiopathic, ulcerative neutrophilic dermatosis. In many cases, PG is associated with a wide variety of different disorders but SLE in association with PG is relatively uncommon. In this article we present the case of a middle aged patient with PG as the initial clinical presentation of SLE. We also provide a brief review of cobalamin deficiency which occurred in our patient and evidence-based management options. Case presentation A 35 years old man presented with a 5 month history of debilitating painful lower limb and scrotal ulcers. This was associated with polyarthralgia and morning stiffness involving both hands. He also complained of swallowing difficulties. He had unintentional weight loss of 10 kg and fatigue. Physical examination revealed alopecia, multiple cervical lymphadenopathies, bilateral parotid gland enlargement and atrophic glossitis. There was Raynaud’s phenomenon noted over both hands and generalised hyper-pigmented fragile skin. Laboratory results disclosed anaemia, leukopenia, hyponatraemia and hypocortisolism. Detailed anaemic workup revealed low serum ferritin and cobalamin level. The autoimmune screen showed positive ANA, anti SmD1, anti SS-A/Ro 52, anti SSA/Ro 60, anti U1-snRNP with low complement levels. Upper gastrointestinal endoscopy with biopsies confirmed atrophic gastritis and duodenitis. Intrinsic factor antibodies and anti-tissue transglutaminase IgA were all negative. Punch biopsies of the leg ulcer showed neutrophilic dermatosis consistent with pyoderma gangrenosum. Based on the clinical findings and positive immunologic studies, he was diagnosed as systemic lupus erythematosus. His general condition improved substantially with commencement of corticosteroids, immunosuppressants and vitamin supplements. Conclusions We report a case of PG as the first manifestation of SLE which was treated successfully with immunosuppressants and vitamin supplements. Our report highlighted the need to consider connective tissue diseases such as SLE in a patient presenting with PG in order for appropriate treatment to be instituted thereby achieving a good outcome.

Abstract Background Hereditary intrinsic factor deficiency is a rare disease characterized by cobalamin deficiency with the lack of gastric intrinsic factor because of gastric intrinsic factor (GIF) mutations. Patients usually present with cobalamin deficiency without gastroscopy abnormality and intrinsic factor antibodies. Case presentation A Chinese patient presented with recurrent severe anemia since age 2 with low cobalamin level and a mild elevation of indirect bilirubin. The hemoglobin level normalized each time after intramuscular vitamin B12 injection. Gene test verified a c.776delA frame shift mutation in exon 6 combined with c.585C > A nonsense early termination mutation in exon 5 of GIF which result in the dysfunction of gastric intrinsic factor protein. The hereditary intrinsic factor deficiency in literature was further reviewed and the ancestry of different mutation sites were discussed. Conclusions A novel compound heterozygous mutation of GIF in a Chinese patient of hereditary intrinsic factor deficiency was reported. It was the first identified mutation of GIF in East-Asia and may indicate a new ancestry.

Introduction: Clinical manifestations of vitamin B12 deficiency are mostly non-specific. An entity called subclinical deficiency has become popular where the need has arisen to perform costly investigations which indicate functional deficiency of vitamin B12 even when vitamin B12 levels are normal. These factors pose a challenge in planning management of patients. Aims and objectives : The study was conducted as an attempt to identify affordable and credible laboratory indicators of vitamin B12 deficiency which can be used as screening tests before choosing patients for further evaluation or treatment. Material and Methods : This was a time bound cross-sectional study where 100 adult patients who had undergone the following investigations were randomly chosen: Complete Blood Count with red cell indices, serum bilirubin and serum vitamin B12 levels. The sensitivity, specificity and predictive values (positive-PPV and negative-NPV) of the variables that could hypothetically identify vitamin B12 deficiency, both individually or in combinations were calculated and compared. Results and conclusion : Hemoglobin, MCV (Mean Corpuscular Volume), MCH (Mean Corpuscular Hemoglobin), platelets and bilirubin were not equally distributed between vitamin B12 deficient and normal groups(p values for these variables were 0.029, 0.000, 0.000, 0.003 and 0.029 respectively).When these variables were tested individually and in combination, the combination of [MCV=95 fl or MCH=30 pg or Platelets =1.4 lakh/µl or Bilirubin =1 mg/dl] had sensitivity of 68.2%, specificity of 85.7%, PPV of 78.9% and NPV of 77.4%. This proposed combination used as a screening test has potential for wide application considering its simplicity and cost advantage.

Introduction : Prevalence of vitamin B12 deficiency is believed to increase with aging. The wide and non-specific spectrum of clinical presentations in patients poses a tough challenge to physicians suspecting vitamin B12 deficiency. Objectives : This study was conducted to collect data on prevalence and clinical features of vitamin B12 deficiency in apparently healthy elderly population visiting hospitals, as the results could help rationalize and direct the appropriate management of vitamin B12 status in elderly. Methods : This was a time bound cross sectional study where apparently healthy individuals >50 years of age were interviewed, examined and investigated in order to study their vitamin B12 concentrations and associated clinical profile. Results: A total of 103 participants were included. The mean vitamin B12 level of the study population was 327.07 pg/ml (S.D= 268.00). In the study, 43.7% (n=45 patients) had low vitamin B12 levels (vitamin B12 deficiency) and 17.5 % (n=18 patients) had subnormal vitamin B12 levels. Among all the symptoms recorded neurological followed by cardiovascular symptoms were more commonly recorded in the patients with vitamin B12 deficiency. Distal dysesthesia was more commonly present in patients with deficient (p 0.044) than in patients with normal vitamin B12 levels. Ataxia and Romberg’s sign positivity were more common in patients with vitamin B12 deficiency when compares to normal vitamin B12 levels (p 0.002 and 0.006, respectively). Conclusion: The study shows that vitamin B12 deficiency is a common problem among elderly and the treating physician should have high index of suspicion when they present with neurological complaints.

Abstract Autoimmune polyglandular syndromes (APS) are rare disorders characterized by auto‐destruction of endocrine and non‐endocrine organs by organ‐specific antibody‐directed T‐lymphocytic infiltration. This case highlights a 29‐year‐old Caucasian man with vitiligo found to have significant neurological abnormalities in the setting of newly diagnosed pernicious anemia and thyroid autoimmune disease.

Acquired vitamin B12 (vB12) deficiency (vB12D) of newborns is relatively frequent as compared with the incidence of inherited diseases included in newborn screening (NBS) of different countries across the globe. Infants may present signs of vB12D before 6 months of age with anemia and/or neurologic symptoms when not diagnosed in asymptomatic state. The possibility of identifying vitamin deficient mothers after their pregnancy during the breastfeeding period could be an additional benefit of the newborn screening. Vitamin supplementation is widely available and easy to administer. However, in many laboratories, vB12D is not included in the national screening program. Optimized screening requires either second-tier testing or analysis of new urine and blood samples combined with multiple clinical and laboratory follow ups. Our scope was to review the physiologic fate of vB12 and the pathobiochemical consequences of vB12D in the human body. Particular emphasis was put on the latest approaches for diagnosis and treatment of vB12D in NBS.

Iron deficiency is known to aggravate the prognosis of patients with heart failure. Iron has functions in the mitochondrial respiratory chain. In patients with reduced mitochondrial respiration, the mitochondrial ratio between the level of nicotinamide adenine dinucleotide and its reduced form decreases. Due to the mitochondrial-lysosomal interplay, decreased mitochondrial respiration also leads to inhibition of lysosomal hydrolysis. As a result, cobalamin and iron will be trapped in lysosomes. This will, even if iron and cobalamin have been consumed and absorbed in sufficient amounts, lead to their functional deficiencies.1 Functional iron deficiency can further impede mitochondrial respiration. Increased plasma levels of methylmalonic acid were shown to predict all-cause and cardiovascular mortality in the general population. Treatments targeting mitochondrial and lysosomal function may correct the functional deficiencies and improve prognosis in a subgroup of patients with heart failure, notably those with skeletal muscle wasting. Methylmalonic acid levels may be used for monitoring response to treatment, thereby identifying patients of the subgroup in which disease outcome may improve.

Abstract Disorders of cobalamin (vitamin B12) metabolism are increasingly recognized in small animal medicine and have a variety of causes ranging from chronic gastrointestinal disease to hereditary defects in cobalamin metabolism. Measurement of serum cobalamin concentration, often in combination with serum folate concentration, is routinely performed as a diagnostic test in clinical practice. While the detection of hypocobalaminemia has therapeutic implications, interpretation of cobalamin status in dogs can be challenging. The aim of this review is to define hypocobalaminemia and cobalamin deficiency, normocobalaminemia, and hypercobalaminemia in dogs, describe known cobalamin deficiency states, breed predispositions in dogs, discuss the different biomarkers of importance for evaluating cobalamin status in dogs, and discuss the management of dogs with hypocobalaminemia.

Introduction:Cobalamin (Cbl) deficient infants are mostly outpatients. Medical literature is very limited concerning infants with severe Cbl deficiency requiring intensive care. The aim of this study was to describe infants requiring intensive care whose health issues were primarily related to Cbl deficiency.Methods:This is a single-center retrospective observational study performed at the pediatric intensive care unit at a children’s hospital. Patients aged 6-24 months with low serum Cbl level coexisting with cytopenia (s) and/or macrocytosis, high levels of iron, ferritin and transferin saturation and whose clinical symptoms necessitating intensive care at diagnosis and resolving after Cbl therapy were included. Infants with chronic diseases and birth asphyxia history were excluded.Results:Seven infants were included in the study. The mean age and Cbl level at presentation was 11±5 months and 50±27 pg/mL, respectively. The presenting complaints were diarrhea, vomiting, difficulty swallowing, seizure, respiratory distress and cyanosis after feeding. Three patients needed mechanical ventilation. Megaloblastic changes were detected in five patients who underwent bone marrow aspiration. Cerebral atrophy was found in six of the patients on cranial imaging. Only one patient developed neurological disability during long-term follow-up.Conclusion:This retrospective study was performed to emphasize the importance of Cbl deficiency in infants requiring intensive care or who had serious deterioration of organ functions. Cbl deficiency in children may lead to life-threatening complications such as respiratory failure or neurological disorders. Prompt diagnosis and immediate treatment may not only be life saving but also improves quality of life in long-term follow-up.

Cobalamin (vitamin B12) deficiency is one of the major factors causing degenerative changes in the nervous system and, thus, various neurological and psychiatric symptoms. The underlying cellular mechanism of this phenomenon is not yet fully understood. An accumulation of senescent astrocytes has been shown to contribute to a wide range of pathologies of the nervous system, including neurodegenerative disorders. This study aimed to investigate whether cobalamin deficiency triggers astrosenescence. After inducing cobalamin deficiency in normal human astrocytes in vitro, we examined biomarkers of cellular senescence: SA-β-gal, p16INK4A, and p21Waf1/Cip1 and performed cell nuclei measurements. The obtained results may contribute to an increase in the knowledge of the cellular effects of cobalamin deficiency in the context of astrocytes. In addition, the presented data suggest a potential causative agent of astrosenescence that has not been proven to date.

This is the case of an elderly patient with a 40-year history of stomach ulcer, whose relatives perceived behavioral changes for the last two months. Those changes progressively included disorientation, psychomotor agitation, negativism and delirium of persecution, which caused him to be brought to the emergency room. He also showed marked pallor and multiple ecchymosis, due to which he was hospitalized in our service and diagnosed with reversible dementia caused by pernicious anemia. Pancytopenia and neurological changes were also found. The patient responded favorably to the administration of vitamin B12

Vitamin metabolic disorders can cause diverse dysfunctions of both the peripheral and central nervous systems. There is conclusive evidence that cyanocobalamin (vitamin B12) and folic acid deficiencies may lead to diminished cognitive functions even to the extent of developing dementia. Cognitive impairments may be accompanied by involvement of other regions of the central nervous system, the corticospinal tract in particular, less frequently by brainstem and cerebellar disorders. Changes in nervous system functions in the presence of cyanocobalamin deficiency may predominate in the clinical picture, ahead of the occurrence of hematological changes. The paper considers the possible mechanisms for involvement of brain neurons in deficiency of cyanocobalamin and in that of folic acid in particular in patients with hyperhomocysteinemia. The low serum concentration of folic acid or cyanocobalamin in the elderly raises the risk of developing Alzheimer’s disease in future (by almost twice) and vascular dementia. The authors give the results of randomized clinical trials evaluating the efficacy of the vitamins used in patients with cognitive impairments. Thus, there are data that the use of cyanocobalamin in patients with lacunar infarcts and moderate cognitive impairments may give rise to their complete recovery and reduce the risk of depressive disorders. Intramuscular cyanocobalamin used in a daily dose of 1000 μg for 5 days, then 1000 μg once monthly is demonstrated to be efficacious. This therapy may be effective in patients with different types of dementia and cognitive diminution, primarily in those with these conditions and its serum concentration of less 150 pmol/l. Among the side effects while taking folic acid, there may be higher incidence rates of convulsive attacks. A number of trials have shown the efficacy of cyanocobalamin, pyridoxine, and folic acid in preventing acute cerebral ischemic episodes; however, not all the investigations could confirm this relationship. This may be related to patients’ age, therapy duration, blood inflammatory marker concentrations, and other factors.

Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. It has been identified as one of the most common lifelong disorders on a worldwide basis. Enteropathy in CD is thought to be the final consequence of an abnormal immune reaction, showing features of both an innate and adaptive response to gluten prolamins. The clinical spectrum is wide, including cases with either typical intestinal or atypical extra intestinal features, or silent forms. Anemia has frequently been reported as the only manifestation or the most frequent extra-intestinal symptom of CD. The only available treatment consists in dietary exclusion of grains containing gluten.

OBJECTIVE: The imbalance between neurotoxic cytokine tumor necrosis factor-α (TNF-α) and neurotrophic cytokines epidermal growth factor (EGF) and interleukin-6 (IL-6) plays a role in the pathogenesis of cobalamin (Cbl) deficiency-induced neuropathy. The aim of this study was to evaluate autonomic nervous system dysfunction and to look for any relationship between autonomic nervous system disturbances and serum cytokine levels (TNF-α, EGF, IL-6) in patients with Cbl deficiency. METHODS: Serum levels of TNF-α, EGF and IL-6 were studied in patients with Cbl deficiency (n=41) and a healthy control group (n=17) and after 3 months in patients who underwent Cbl replacement therapy (n=22). All patients with Cbl deficiency underwent electrophysiological studies (EPS) for the diagnosis of neuropathy. Statistical analysis was performed using SPSS for Windows 11.5 software. RESULTS: With EPS, 29 of 41 Cbl-deficient patients (70.73%) demonstrated neurological dysfunction [3 (7.32%), 19 (46.34%) and 7 (17.07%) patients with sensorimotor peripheral neuropathy, parasympathetic, and sympathetic autonomic dysfunction, respectively]. Although there was no significant difference in serum levels of EGF and IL-6 between patients with versus without autonomic dysfunction, levels were significantly lower in Cbl- deficient patients than healthy controls. CONCLUSION: Presence of autonomic dysfunction seems to be a frequent neurological finding in patients with Cbl deficiency. However, we could not find any relationship between serum cytokine levels and autonomic dysfunction by EPS.

neurotrophiccytokines epidermal growth factor (EGF) and interleukin-6 (IL-6) plays a role in the pathogenesisof cobalamin (Cbl) deficiency-induced neuropathy. The aim of this study was to evaluate autonomicnervous system dysfunction and to look for any relationship between autonomic nervous systemdisturbances and serum cytokine levels (TNF-

Background: In India, 60-90% of adolescent suffer from anemia. Studies have documented folate, ferritin, and cobalamin deficiencies to be the major causes of nutritional anemia. However, limited data is available on the prevalence of folate, ferritin, and cobalamin deficiencies amongst adolescent from India. Objectives: The present study was carried out to find out the magnitude of folate, ferritin, and cobalamin deficiencies amongst adolescent of 11-18 years of age in National Capital Territory (NCT) of Delhi, India. Materials and Methods: A cross-sectional, school-based study was conducted in NCT of Delhi, India in the year 2010-2011. About 347 adolescent belonging to low- (LIG), middle- (MIG), and high-income groups (HIG) were selected using the probability proportionate to size (PPS) sampling methodology. Serum ferritin, serum folate, and serum cobalamin levels were determined by the enzyme-linked immunosorbent assay (ELISA) method, radioimmunoassay (RIA) method, and radioisotopic method, respectively. Hemoglobin (Hb) estimation was done by cyanmethemoglobin method in all the blood samples collected. Results: The prevalence of deficiency of ferritin in HIG, MIG, and LIG categories of adolescent was found to be 52.9, 67, and 58.8%, respectively. In the HIG, MIG, and LIG categories of adolescent, the prevalence of folate deficiency was 22.5, 40.4, and 52.2%, respectively. The prevalence of deficiency of cobalamin in HIG, MIG, and LIG categories of adolescent was 47.1, 80.7 and 87.5%, respectively. About 48, 66.1, and 68.4% of adolescent in the HIG, MIG, and LIG categories, respectively had Hb levels less than 12 g/dL and were found to be suffering from anemia. Conclusions: A high prevalence of anemia existed along with deficiency of ferritin, cobalamin, and folate amongst adolescent. The strategies for prevention of anemia amongst adolescent in India should also include cobalamin along with iron and folate supplementation for prevention and control of nutritional anemia. Primary care physicians should suspect all the three causes for anemia.