Abstract
A new metabolic disorder characterized by severe congenital microcephaly, death within the first year, and severe 2-ketoglutaric aciduria has been found among the Old-Order Amish of Lancaster County, Pennsylvania. Amish lethal microcephaly segregates as an autosomal recessive disorder and has an unusually high incidence of at least 1 in 500 births. When the infants are well, the urine organic acid profiles show isolated, extreme elevations of 2-ketoglutaric acid. However, during otherwise simple viral illnesses, the infants often develop a metabolic acidosis, which may follow a lethal course. Cranial magnetic resonance imaging of a single patient showed a smooth, immature brain similar to that of a 20-week fetus except for a moderate degree of cerebellar vermal hypoplasia. Assay of 2-ketoglutarate dehydrogenase in cultured lymphoblasts of one patient showed normal activity. Amish lethal microcephaly maps to 17q25 and may be caused by a defect in a mitochondrial inner membrane protein functioning as a 2-ketoglutarate transporter.
Original language | English (US) |
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Pages (from-to) | 318-326 |
Number of pages | 9 |
Journal | American journal of medical genetics |
Volume | 112 |
Issue number | 4 |
DOIs | |
State | Published - Nov 1 2002 |
Externally published | Yes |
Keywords
- 17q25
- 2-ketoglutaric acid
- Amish
- Microcephaly
- Mitochondrial disease
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)