PPM1K defects cause mild maple syrup urine disease: The second case in the literature

Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by the insufficient catabolism of branched-chain amino acids. BCKDHA, BCKDHB, DBT, and DLD encode the subunits of the branched-chain α-ketoacid dehydrogenase complex, which is responsible for the catabolism of these amino acids. Biallelic pathogenic variants in BCKDHA, BCKDHB, or DBT are characteristic of MSUD. In addition, a patient with a PPM1K defect was previously reported. PPM1K dephosphorylates and activates the enzyme complex. We report a patient with MSUD with mild findings and elevated BCAA levels carrying a novel homozygous start-loss variant in PPM1K. Our study offers further evidence that PPM1K variants cause mild MSUD.     

A nonsense mutation (R242X) in the branched-chain α-keto acid dehydrogenase E1α subunit gene (BCKDHA) as a cause of maple syrup urine disease

Mutation analysis of DNA from cultured amniocytes with absent branched-chain α-ketoacid dehydrogenase activity revealed a C to T transition producing a nonsense mutation (R242X) in exon 7 of the gene encoding the E1a subunit of this multienzyme complex (BCKDHA). This pregnancy occured in a large consanguinous pedigree with multiple individuals with maple syrup urine disease (MSUD). PCR amplification of the region surrounding exon 7 allowed the identification of this mutation as well as two other previously identified mutations which cause MSUD. hum Mutat 12:136, 1998. © 1998 Wiley-Liss, Inc.