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S ‐adenosylhomocysteine hydrolase deficiency: two siblings with fetal hydrops and fatal outcomes
Author(s) -
Grubbs Randall,
Vugrek Oliver,
Deisch Jeremy,
Wagner Conrad,
Stabler Sally,
Allen Robert,
Barić Ivo,
Rados Marko,
Mudd S. Harvey
Publication year - 2010
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-010-9171-x
Subject(s) - hypoalbuminemia , medicine , endocrinology , fetus , hypotonia , abnormality , sibling , hydrops fetalis , gastroenterology , biology , pregnancy , genetics , psychology , developmental psychology , psychiatry
Abstract This paper reports the clinical and metabolic findings in two sibling sisters born with fetal hydrops and eventually found to have deficient S ‐adenosylhomocysteine hydrolase (AHCY) activity due to compound heterozygosity for two novel mutations, c.145C>T; p.Arg49Cys and c.257A>G; p.Asp86Gly. Clinically, the major abnormalities in addition to fetal hydrops (very likely due to impaired synthetic liver function) were severe hypotonia/myopathy, feeding problems, and respiratory failure. Metabolic abnormalities included elevated plasma S ‐adenosylhomocysteine, S ‐adenosylmethionine, and methionine, with hypoalbuminemia, coagulopathies, and serum transaminase elevation. The older sister died at age 25 days, but the definitive diagnosis was made only retrospectively. The underlying genetic abnormality was diagnosed in the second sister, but treatment by means of dietary methionine restriction and supplementation with phosphatidylcholine and creatine did not prevent her death at age 122 days. These cases extend the experience with AHCY deficiency in humans, based until now on only the four patients previously identified, and suggest that the deficiency in question may be a cause of fetal hydrops and developmental abnormalities of the brain.