The Prenatal Diagnosis of Glutaric Aciduria Type II, using Quantitative GC-MS

Abstract

Glutaric aciduria type II (multiple acyl-CoA dehydrogenase deficiency) (McKusick 23168) is an inherited metabolic disease associated clinically with severe hypoglycaemia, metabolic acidosis, hepatomegaly, hypotonia, neurological symptoms and death in the neonatal period. Biochemically it is characterised by increased urinary excretion of several organic acids, particularly glutarate, 2-hydroxyglutarate, 3-hydroxy-isovalerate, adipate and other dicarboxylic acids, and isovalerylglycine and other acylglycines. Pathologically, there is fatty infiltration of the liver and heart and a number of cases have been described in which grossly enlarged polycystic kidneys occur together with severe dysmorphic features. We report here prenatal diagnosis for severe neonatal dysmorphic glutaric aciduria type II using both chemical analysis of amniotic fluid supernatant with quantitative selected ion monitoring (SIM) on GC-MS and also enzymology on cultured amniocytes. Affected and unaffected fetuses have been correctly predicted with results being duplicated in three independent laboratories.