Methylmalonyl coenzyme A (
CoA)
epimerase (MCE) converts D-
methylmalonyl-CoA into L-
methylmalonyl CoA in the final common degradation pathway of
valine,
isoleucine,
methionine,
threonine, odd-chain
fatty acids, and
cholesterol side chains.
Methylmalonyl-CoA epimerase deficiency is an ultra-rare autosomal recessive disorder where
methylmalonic acid, methylcitrate,
3-hydroxypropionate, and
propionylcarnitine are accumulated. We describe two novel pediatric patients and review the previously reported cases of MCE deficiency. Including our two novel patients, at least 24 cases of MCE deficiency have been described, with a broad clinical spectrum ranging from asymptomatic to severely neurologically impaired patients. Our patients are siblings of Arabic origin who presented with metabolic decompensation with
coma and
epilepsy during infancy.
Methylmalonic aciduria was disclosed, L-
methylmalonyl-CoA mutase deficiency was assumed, and they were treated accordingly. When first seen in our country, aged 10 and four years, respectively, both presented severe
intellectual disability and spasticity. The younger had an ataxic gait, and the older was wheelchair-ridden. The study of the MMUT, MMAA, MMAB, and MMADHC genes was normal. Subsequently, the pathogenic variant c.139C>T (p.Arg47*) in the MCEE gene was identified in homozygosity in both patients, leading to the diagnosis of MCE deficiency (Online Mendelian Inheritance in Man (OMIM®) 251120, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, MD, USA). Most patients were homozygous for that variant (83% of the alleles). Correct diagnosis allowed treatment adequacy and genetic counseling.
Methylmalonyl-CoA epimerase deficiency shares a similar biochemical profile with other rare
genetic disorders. Patients present with overlapping clinical features with predominant
neurological manifestations; genetic testing is indispensable for diagnosis. We found no association between genotype and biochemical and clinical phenotypes.