The most common clinical syndromes associated with 3-methyl-glutaconic (MGC) aciduria are reviewed by researchers from various centers; Courtwright and Summers Metabolic Disease Center and Baylor Research Institute, Dallas, TX; Shaare Zedek Medical Center, Jerusalem; Free University of Amsterdam; Loewenstein Hospital, Tel-Aviv Univ, Raanana, Israel; and Kennedy Krieger Institute, Baltimore, MD. Three distinct syndromes are described: Type I 3-MG-CoA Hydratase Deficiency.- (autosomal recessive) 3 patients had delayed speech and macrocephaly, increased urinary excretion of 3-MGC acid, 3-M Glutaric(MGR) and 3-hydroxyisovaleric acids, elevated CPK and serum carnitine, and hypoglycemia. Urinary 3-MGC excretion is decreased by restriction of L-leucine intake. Type II Barth Syndrome.- (X-linked) dilated cardiomyopathy, recurrent infection, neutropenia, growth retardation. Improves with age. Increased urinary excretion of 3-MGC, 3-MGR, fumaric, and 2-ethylhydracrylic acids. Type III Costeff Optic Atrophy Syndrome.- (autosomal recessive) A Behr-like syndrome described in 39 patients of Iraqi-Jewish origin living in Israel. Optic atrophy, choreoathetosis, spastic paraparesis, cerebellar ataxia. Nonprogressive. 3-MGC and 3-MGR aciduria.
An Unclassified 3-MGC aciduria includes patients presenting in the first year of life with neurologic impairment, seizures, retinal pathology, and a fatal course. Cardiomyopathy, hepatic dysfunction, hypoglycemia, lactic acidosis, and dysmorphia are associated manifestations. Defects of the mitochondrial respiratory chain are suggested. [1]
COMMENT. This review will assist the neurologist in the differential diagnosis of patients with 3-MGC aciduria. Some cases are multisystemic and progressive, with onset from birth to several years, some are primarily neurologic and non-progressive, while others involve the heart muscle and may improve with age.