Title:The association of MMUT mutation (NM_000255.4:c.976A>G) with wide spectrum clinical manifestations in a child affected with methylmalonic acidaemia

Author:Yadollah Zahed Pasha, Alireza Paniri, Mousa Ahmadpour-kacho, Sadegh Fattahi, Nafiseh Yazarlou and Haleh Akhavan-Niaki

Abstract:Methylmalonic acidemia (MMA) is a rare autosomal recessive disorder caused by methylmalonyl CoA mutase (MMUT) deficiency which converts methylmalonyl-coenzyme A (CoA) to succinyl-CoA. Patients with MMA present a wide spectrum of clinical manifestations including lethargy, vomiting, hypotonia, seizure, acid-base disturbances, and tachycardia. Here, we report the case of a six-day-old infant suffering from poor feeding, acid-base imbalance, weak reflexes (grasping, sucking, and moro reflex), seizures, hypotonia, tachypnea, and tachycardia. Results obtained from whole exome sequencing (WES) for the proband identified a homozygous mutation in MMUT (NM_000255.4:c.976A>G (p.Arg326Gly)). The mutation was confirmed in both parents by Sanger sequencing. Biochemical analysis demonstrated significantly increased levels of methylmalonic acid and 3-hydroxypropionic acid excretions as well as elevated levels of glycine, tyrosine, lysine, and decreased levels of methionine in serum (elevated propinylcarnitine). Both his non-consanguineous parents were identified to be heterozygous for this mutation.
Keywords: Methylmalonic acidemia; MMUT; Methylmalonyl-CoA mutase; Neonatal Screening; Hyperammonemia.
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