Linked Life Data

9427140

Source:http://linkedlifedata.com/resource/pubmed/id/9427140

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1998-2-18
pubmed:abstractText
This first detailed report of a female patient with functional methionine synthase deficiency due to the cblE defect describes treatment with several vitamins and cofactors and clinical progress for 17 years. Before treatment, major findings were microcephaly, psychomotor retardation, episodic reduced consciousness, megaloblastic anaemia, increased plasma free homocystine (> 20 mumol/L), low plasma methionine (< 10 mumol/L) and increased excretion of formiminoglutamate. On high-dose folic acid, biochemical abnormalities such as formiminoglutamate excretion and homocystinuria nearly normalized, but clinical and haematological abnormalities remained. On replacement of folate with methylcobalamin, alertness, motor function, speech and the electroencephalogram improved, biochemical features were similar, but the mean corpuscular volume increased. The best control was observed on a combination of folate and methylcobalamin. At 17 years of age she remains severely mentally retarded. In cultured fibroblasts methionine synthesis was reduced (0.03 nmol/mg/per 16 h, controls 2.4-6.9); methionine synthase activity was normal under high reducing conditions but decreased on limiting the reducing agent, dithiothreitol, to 5 mmol/L (18% of total, controls 51-81%); formation of methylcobalamin was low (4.5% of total cobalamins, control 57.5%) and complementation studies indicated the cblE defect. Methionine formation showed only minor increases in cells grown in folate- or cobalamin-supplemented medium. Serine synthesis, which was low in normal medium, increased with cobalamin supplementation. These studies suggest further heterogeneity within cblE mutants, show the difficulty of establishing the enzyme defect in vitro, and indicate a role for folate in addition to cobalamin in treatment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0141-8955
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
731-41
pubmed:dateRevised
2007-3-21
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Folate-responsive homocystinuria and megaloblastic anaemia in a female patient with functional methionine synthase deficiency (cblE disease).
pubmed:affiliation
Basel University Children's Hospital, Switzerland.
pubmed:publicationType
Journal Article, Case Reports, Research Support, Non-U.S. Gov't