Abstract
Elevated methylmalonic acid in five asymptomatic newborns whose fibroblasts showed decreased uptake of transcobalamin-bound cobalamin (holo-TC), suggested a defect in the cellular uptake of cobalamin. Analysis of TCblR/CD320, the gene for the receptor for cellular uptake of holo-TC, identified a homozygous single codon deletion, c.262_264GAG (p.E88del), resulting in the loss of a glutamic acid residue in the low-density lipoprotein receptor type A-like domain. Inserting the codon by site-directed mutagenesis fully restored TCblR function.
Publication types
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Case Reports
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Antigens, CD / chemistry
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Antigens, CD / genetics*
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Base Sequence
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Cells, Cultured
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DNA Mutational Analysis
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Female
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Fibroblasts / metabolism
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Homocysteine / metabolism
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Humans
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Infant
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Infant, Newborn
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Metabolism, Inborn Errors / diagnosis*
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Metabolism, Inborn Errors / genetics*
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Methylmalonic Acid / metabolism
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Molecular Sequence Data
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Mutation / genetics*
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Neonatal Screening / methods*
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Pregnancy
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Receptors, Cell Surface
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Transcobalamins / metabolism*
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Vitamin B 12 / metabolism*
Substances
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Antigens, CD
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CD320 protein, human
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Receptors, Cell Surface
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Transcobalamins
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Homocysteine
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Methylmalonic Acid
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Vitamin B 12