title: S-adenosylhomocysteine hydrolase deficiency: two siblings with fetal hydrops and fatal outcomes.
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.
authors.affiliation: Pediatrix Medical Group of Texas, Fort Worth, TX, USA.
authors.forename: Randall
authors.initials: R
authors.lastname: Grubbs
authors.forename: Oliver
authors.initials: O
authors.lastname: Vugrek
authors.forename: Jeremy
authors.initials: J
authors.lastname: Deisch
authors.forename: Conrad
authors.initials: C
authors.lastname: Wagner
authors.forename: Sally
authors.initials: S
authors.lastname: Stabler
authors.forename: Robert
authors.initials: R
authors.lastname: Allen
authors.forename: Ivo
authors.initials: I
authors.lastname: Barić
authors.forename: Marko
authors.initials: M
authors.lastname: Rados
authors.forename: S Harvey
authors.initials: SH
authors.lastname: Mudd
mesh_terms: D043383:Adenosylhomocysteinase / Q000172:deficiency* / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D015160:Hydrops Fetalis / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics / Q000401:mortality; D007223:Infant; D007231:Infant, Newborn; D008661:Metabolism, Inborn Errors / Q000150:complications / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality; D035781:Siblings
chemical_list: D043383:Adenosylhomocysteinase