In conclusion these patients raise questions about treatment strategies and the mechanism behind the development of atypical HUS in CblG deficiency. Inborn errors of cellular cobalamin (Cbl) metabolism are disorders of decreased production of adenosylcobalamin or methylcobalamin either both or alone, cofactors for methylmalonyl CoA-mutase and methionine synthase, respectively. cblC deficiency is due to a defect in Cbl(III) to Cbl(II) conversion resulting in accumulation of methylmalonic acid and homocysteine. Neonatal presentation is typical but milder forms may present later with neurological deterioration. Features uncommon in inborn errors of metabolism such as dysmorphisms, ocular abnormalities, and congenital malformations are seen in cblC. Hydrocephalus, a recognised complication has been previously noted postnatally only and not secondary to cerebral haemorrhage. We describe a case with prenatal presentation of right sided ventriculomegaly and grade three intraventricular hemorrhage (IVH) diagnosed at 28 weeks gestation by ultrasound and MRI. Newborn screening showed elevated C3 acylcarnitine and confirmatory investigations led to the diagnosis of cblC disorder. A congenital bleeding disorder was excluded. At present his development is normal on hydroxycobalamin and betaine therapy despite marked right ventriculomegaly. To our knowledge, this is the first description of prenatal IVH and hydrocephalus associated with the cblC disorder and only the second report of prenatal abnormality. cblC disorder remains one of the few inborn errors of metabolism associated with prenatal malformations. Conclusions: Brain folate is essential for more than 100 metabolic processes in the nervous system and influences neurotransmitter turnover. The presence of FR autoantibodies over time predisposes to episodes associated with CNS folate depletion. Our findings may explain the alternating negative and positive symptoms characteristic of schizophrenia and may be due to fluctuations in antibody titer observed. Evaluation for neuro-immunologic causes, including FR autoantibodies is recommended for patients with intractable schizophrenia, who can benefit from folinic acid supplementation. Juvenile Megaloblastic Anaemia 1 (OMIM # 261100) is a rare autosomic disorder characterized by selective cobalamin (vitamin B12) malabsorption and inconstant proteinuria produced by mutations in either CUBN or AMN genes. Amnionless, the gene product of AMN, is a transmembrane protein that binds tightly to the N-terminal end of cubilin, the gene product of CUBN that binds to intrinsic factor-cobalamin complex, in the distal intestine and the proximal renal tubule. We report in two siblings a compound AMN heterozygosity with c.742 C>T, p.Gln248X and c.208-2A>G mutations, that led to premature termination codon in exon 7 and exon 6, respectively and produced a dramatic decrease of receptor activity in urines, despite absence of CUBN mutation and normal affinity of the receptor for intrinsic factor binding. Heterozygous carriers for c.742 T and c.208-2 G had no pathological signs. These results indicate that amnionless is indispensable for the proper luminal expression of cubilin, in humans. Severe mutations in the gastric intrinsic factor (GIF) gene lead to congenital megaloblastic anemia. Little is known on the frequency and influence of GIF variants on the cobalamin (vitamin B12) absorption. We therefore aimed at identifying GIF variants in subjects with biological evidence of cobalamin deficit, in 2200 subjects prospectively recruited in our University hospital (North East of France) during 2 years. The selection criteria included decreased cobalamin, increased homocysteine and/or methylmalonic acid and/or macrocytosis. Among the 2200 subjects, 176 cases presented with hyperhomocysteinemia and/or increased methylmalonic acid, including 45 cases with combined criteria of cobalamin deficit. These 45 cases were compared to 70 controls. Five GIF variants were identified in 14 cases. We report a 13-year old female with Asperger syndrome, epilepsy, sleep disorder, episodic ataxia and tremor. Investigations showed a reduced CSF pyridoxal 5'-phosphate (PLP) (6 nmol/L, range 10-37 nmol/L) with normal CSF monoamine neurotransmitters and low-normal plasma PLP (22 nmol/L, range 15-73 nmol/L). She had reduced whole-blood serotonin (539 nmol/L, range 600-1600 nmol/L), low aromatic amino-acid decarboxylase activity (24.4pmol/min/ml, range 36-129pmol/min/ml) and isolated reduction in plasma tryptophan (14,17,27 μmol/L, range 30-87 μmol/L). Urinary alpha-AASA excretion was normal and sequencing of the pyridox(am)ine 5'-phosphate oxidase gene revealed no mutations. She has shown good improvement on PLP therapy with cessation of seizures, tremor, ataxia and improvement in social functioning. Tryptophan depletion is associated with autistic symptomatology and disturbance of circadian rhythm. PLP deficiency may result in seizures. Plasma tryptophan levels are regulated by the inducible enzyme tryptophan-2, 3-dioxygenase (TDO2) which diverts metabolism of tryptophan into the kynurenine pathway away from the methoxyindole pathway for serotonin and melatonin synthesis. Increased TDO2 activity (via secondary induction/gain-of-function mutation) may lead to the biochemical phenotype described. The mechanism of reduced PLP levels is difficult to explain but, if kynurenine levels are elevated, it may be due to the formation of a Schiff base between PLP and kynurenine. We present two children with early infantile seizures, hypoglycorrhachia and increased CSF lactate. The clinical picture and routine biochemical findings raised the possibility of GLUT1 deficiency (CSF:plasma glucose <0.4) or mitochondrial disease. However urine organic acid analysis was suggestive of biotinidase deficiency, subsequently confirmed by low plasma biotinidase activity and clinical response to biotin. Both infants presented at 2 months with seizures. The CSF:plasma glucose ratios were 0.35 and 0.33 (reference range >0.60) and CSF lactates 5.1 and 6.4 mmol/L (reference range 1.1-2.2 mmol/L). There is an extensive differential diagnosis for infants with early infantile seizures. In the absence of infection, increased CSF lactate concentrations may raise the suspicion of a mitochondrial disorder, while low CSF glucose may be attributed to GLUT1 deficiency. However a low CSF lactate is expected in GLUT1 and low CSF glucose is not a typical feature of mitochondrial disease. Although hypoglycorrhachia is not generally reported in biotinidase deficiency, we suggest this diagnosis should be borne in mind where it occurs with seizures and raised CSF lactate. We speculate that the pyruvate carboxylase deficiency that arises in biotinidase deficiency may be responsible for these biochemical findings, perhaps due to lack of oxaloacetate. Background: Vitamin C is the cofactor in biosynthesis of collagen, catecholamines and iron metabolism.