3-methylglutaconic aciduria type 1 (3-MGA-I) (MIM ID #250950) is an ultra-rare, autosomal recessive organic aciduria, resulting from mutated AUH gene, leading to the deficient 3-methylglutaconyl-CoA hydratase (3-MGH). Only around 40 cases are previously reported, caused by a spectrum of 10 mutations. The clinical spectrum of 3-MGA-I in children is heterogeneous, varying from asymptomatic individuals to mild neurological impairment, speech delay, quadriplegia, dystonia, choreoathetoid movements, severe encephalopathy, psychomotor retardation, basal ganglia involvement. Early dietary treatment with leucine restriction and carnitine supplementation may be effective in improving neurological state in pediatric patients with 3-MGA-I. We presented a girl with 3-MGA-I due to novel AUH gene mutation (homozygous variant c.330 + 5G > A) and confirmed by almost undetectable 3-MGH-enzyme activity, who initially presented with central precocious puberty at an early age of 4.5 years. Precocious puberty might be associated with the 3-MGA-I, as is reported previously in some other metabolic disorders that result in pathologic accumulation of metabolites or toxic brain damage. Therapy with GnRH agonist triptorelin effectively arrested pubertal development.
Keywords: 3-HIVA, 3-hydroxyisovaleric acid; 3-MG, 3-methylglutaric acid; 3-MGA-I; 3-MGA-I, 3-methylglutaconic aciduria type I; 3-MGH, 3-methylglutaconyl-CoA hydratase; 3-methylglutaconic aciduria type 1; AUH gene; C5-OH, 3-hydroxyisovaleryl-carnitine; GnRH agonist; GnRH, Gonadotropin-releasing hormone; IEM, inborn errors of metabolism; LC-MS/MS, Tandem mass spectrometry; LH, luteinizing hormone; MRI, Magnetic resonance imaging; NBS, newborn screening; Precocious puberty; ToL, The Tower of London test; Triptorelin; UCHL, University Children's Hospital Ljubljana.
© 2020 The Authors.