Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028738 (nystagmus)
 7,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cobalamin C (cblC) defects result in decreased activity of both methylmalonyl-CoA mutase and N5-methyltetrahydrofolate:homocysteine methyltransferase (methionine synthase), with subsequent methylmalonic acid-uria and homocystinuria. Patients typically show failure to thrive, developmental delay and megaloblastic anaemia. Vitamin B12 therapy has been beneficial in some cases. We report a now 4-year-old Hispanic girl with cblC disease documented by complementation analysis, with progressive neurological deterioration and worsening head MRI changes while on intramuscular hydroxocobalamin begun at age 3 weeks. Oral carnitine and folic acid were added at age 1 year. Blood levels of methylmalonic acid were reduced to treatment ranges. In the absence of acute metabolic crises, she developed microcephaly, progressive hypotonia and decreased interactiveness. Funduscopic examination was normal at age 13 months. At age 19 months, she developed nystagmus, and darkly pigmented fundi and sclerotic retinal vessels were observed on examination. Her neonatal head MRI was normal. By age 1 year, the MRI showed diffuse white-matter loss with secondary third and lateral ventricle enlargement, a thin corpus callosum, and normal basal ganglia. At age 15 months, progression of the white-matter loss, as well as hyperintense globi pallidi, were present. Interval progression of both grey- and white-matter loss was seen at age 27 months. We therefore caution that progressive neurological deterioration and head MRI abnormalities may still occur in cblC disease, despite early initiation of hydroxocobalamin therapy and improvement in toxic metabolite concentrations in physiological fluids.
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PMID:Progressive neurological deterioration and MRI changes in cblC methylmalonic acidaemia treated with hydroxocobalamin. 1039 92

Cobalamin and its metabolites play a crucial role in DNA synthesis and cellular energy metabolism. Disorders of cobalamin metabolism are rare, autosomal recessive, conditions that present with neurological dysfunction of varying severity. We report a child with cobalamin E defect presenting in early infancy with vertical nystagmus, developmental delay, deceleration in head growth, status epilepticus and leukoencephalopathy, with only mild haematological abnormalities. Resolution of seizures and subsequent improvement in development and head growth was observed following early treatment with parenteral hydroxocobalamin, betaine, folate and methionine, emphasising the importance of early diagnosis and treatment in these conditions.
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PMID:Cobalamin E defect, a rare inborn error of vitamin B12 metabolism: value of early diagnosis and treatment. 2484 21