The molecular basis of glutamate formiminotransferase deficiency

Hilton, John; Christensen, Karen E.; Watkins, David; Raby, Benjamin A.; Renaud, Yannick; Luna, Susana de la; Estivill, Xavier; MacKenzie, Robert E.; Hudson, Thomas J.; Rosenblatt, David S.

doi:10.1002/humu.10281

Cited by 11 publications

(21 citation statements)

References 48 publications

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“…75 This is an autosomal-recessive disorder and the second most common inborn error of folate metabolism. Common features include physical and mental retardation and elevated serum folate.…”

Section: Homocystinuria and Hypomethionemiamentioning

confidence: 99%

Investigation of inter-individual variability of the one-carbon folate pathway: a bioinformatic and genetic review

2009

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“…75 This is an autosomal-recessive disorder and the second most common inborn error of folate metabolism. Common features include physical and mental retardation and elevated serum folate.…”

Section: Homocystinuria and Hypomethionemiamentioning

confidence: 99%

Investigation of inter-individual variability of the one-carbon folate pathway: a bioinformatic and genetic review

2009

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“…In mild cases, FIGLU excretion has been far higher, without an l ‐histidine load, the serum folate was normal and there was slight developmental delay. Mutations in the formiminotransferase‐cyclodeaminase ( FTCD ) gene have now been identified in three patients with the mild phenotype (Hilton et al , 2003). Expression of the mutant enzymes revealed activity levels of 57% and 61% of wild‐type.…”

Section: Inherited Disorders Of Cobalamin and Folatementioning

confidence: 99%

Acquired and inherited disorders of cobalamin and folate in children

Whitehead

2006

Br J Haematol

142

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SummaryCobalamin deficiency in the newborn usually results from cobalamin deficiency in the mother. Megaloblastic anaemia, pancytopenia and failure to thrive can be present, accompanied by neurological deficits if the diagnosis is delayed. Most cases of spina bifida and other neural tube defects result from maternal folate and/or cobalamin insufficiency in the periconceptual period. Polymorphisms in a number of genes involved in folate and cobalamin metabolism exacerbate the risk. Inborn errors of cobalamin metabolism affect its absorption, (intrinsic factor deficiency, Imerslund-Gräsbeck syndrome) and transport (transcobalamin deficiency) as well as its intracellular metabolism affecting adenosylcobalamin synthesis (cblA and cblB), methionine synthase function (cblE and cblG) or both (cblC, cblD and cblF). Inborn errors of folate metabolism include congenital folate malabsorption, severe methylenetetrahydrofolate reductase deficiency and formiminotransferase deficiency. The identification of disease-causing mutations in specific genes has improved our ability to diagnose many of these conditions, both before and after birth.

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“…The gene for this enzyme has been mapped to chromosome 21. Mutations in this gene have been found in 3 patients with glutamate formiminotransferase defi ciency [10] . Since this gene is on chromosome 21, the activity of the enzyme may be increased due to a 50% increase in gene dosage.…”

Section: Discussionmentioning

confidence: 99%

A Folate-Dependent Metabolite in Amniotic Fluid from Pregnancies with Normal or Trisomy 21 Chromosomes

Baggot

Eliseo²,

Kalamarides

et al. 2005

Fetal Diagn Ther

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Introduction: Previous studies have given conflicting results as to whether or not folate metabolism is altered in Down syndrome. Folate is necessary to facilitate metabolism of one-carbon units. Folate accepts one-carbon units from one-carbon unit donors, including formiminoglutamate (FIGLU). Folate deficiency leads to accumulation of FIGLU and impairment of one-carbon unit metabolism. FIGLU is a functional measure of folate deficiency. Materials and Methods: Archived anonymized amniotic fluid specimens were obtained from normal pregnancies and those with Down syndrome. Gas liquid chromatography/mass spectrometry was used to quantitate FIGLU, which is elevated in folate deficiency. A tetra-deuterated FIGLU was used as a standard, and single-ion monitoring was performed. Nonparametric statistical analysis was performed with the Mann-Whitney U test. Results: FIGLU was significantly lower in pregnancies with Down syndrome. The median FIGLU level was 0.9 µmol/l in amniotic fluid from fetuses with Down syndrome. The median FIGLU level was 1.3 in amniotic fluid from control fetuses. This difference was statistically significant (p = 0.009). No statistically significant differences were found with histidine or glutamate. Discussion: There was no evidence of folate deficiency. FIGLU was decreased, not increased. Decreased FIGLU might result from accelerated activity of one or more genes on chromosome 21, by a gene dosage effect. Genes which might explain the reduced FIGLU include one which degrades FIGLU (glutamate formiminotransferase-cyclodeaminase), one which participates in purine synthesis, and one which degrades homocysteine (cystathionine-β-synthase).

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The molecular basis of glutamate formiminotransferase deficiency

Abstract: The original article to which this Erratum refers was published in Human Mutation 22:67–73

Cited by 11 publications

References 48 publications

Investigation of inter-individual variability of the one-carbon folate pathway: a bioinformatic and genetic review

Investigation of inter-individual variability of the one-carbon folate pathway: a bioinformatic and genetic review

Acquired and inherited disorders of cobalamin and folate in children

A Folate-Dependent Metabolite in Amniotic Fluid from Pregnancies with Normal or Trisomy 21 Chromosomes

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