3-Methylglutaconyl-CoA hydratase deficiency: a new patient with speech retardation as the leading sign.

3-Methylglutaconyl (3-MG)-CoA hydratase (EC 4.2.1.18) catalyses the fourth step in leucine catabolism by converting 3-MG-CoA into 3-hydroxy-3-methylglutaryl (3-HMG)-CoA. Deficiency of 3-MG-CoA hydratase has been defined as 3-methylglutaconic (3-MGC) aciduria type I (McKusick 250950) presenting with increased urinary excretion of 3-MGC, 3-methylglutaric (3-MGR) acid and 3-hydroxyisovaleric (3-HIV) acid and with normal amounts of 3-hydroxy-3-methylglutaric (3-HMG) acid. Additional types of 3-MGC aciduria with normal activities of 3-MG-CoA hydratase have been classified (Gibson et al 1993): type II seems to be of X-linked inheritance and is associated with cardiomyopathy, growth retardation and neutropenia (Kelley et al 1989). Type III has been described as the Costeff Iraqi-Jewish optic atrophy syndrome (Costeff et al 1989). Another type (type IV, unclassified) comprises a heterogeneous group of patients with progressive neurological symptoms. In contrast to 3-MGC aciduria type I, the origin of the specific organic aciduria in these entities is unknown. Since 3-HIV acid seems to be excreted only in patients with deficient 3-MG-CoA hydratase activity, it is an important parameter for differentiation between type I and the other types. Owing to the variability of the clinical picture of the nine patients with deficiency of 3-MG-CoA hydratase reported so far, a specific phenotype of 3-MGC aciduria type I has not yet been established. There seem to be a benign and a more severe form: in several patients the only symptoms were delayed speech development, mild psychomotor retardation and attention deficits (Duran et al 1982; Gibson et al 1992; Sewell et al 1999). Three of the reported patients, however, presented with severe neurological symptoms including spastic quadriplegia, dystonic movements, hypotonia and marked psychomotor retardation in two patients as well as coma and seizures during an episode of Reye syndrome in another patient with speech retardation (Gibson et al 1998; Hou and Wang 1995; Shoji et al 1999). We report on a new patient with a mild clinical presentation of 3-MGC aciduria type I.