maple syrup urine disease symptoms in adults

Pathogenic variants in the gene encoding the BCKDC kinase have not been identified.īCKDC plays a key role in the metabolism of BCAAs for energy production and synthesis of fatty acids and cholesterol through gluconeogenesis ( figure 1). There are case reports of a mild form of MSUD due to homozygous variants in the protein phosphatase, Mg 2+/Mn 2+ dependent 1K ( PPM1K) gene encoding the BCKDC phosphatase and variable increases of branched-chain amino acids (BCAAs) due to deficiency of one of the two branched-chain aminotransferase (BCAT) enzymes. Founder variants are identified in populations with a particularly high prevalence of MSUD (eg, Mennonites, Amish). No strict genotype-phenotype correlation exists in patients with MSUD. Homozygous or compound heterozygous variants in any of these genes can cause any of the forms of MSUD. The sequences of all genes are fully characterized, including regulatory elements. The mode of inheritance is autosomal recessive. These genes map to human chromosomes 19q13.1-q13.2 (BCKDHA), 6p22-p21 ( BCKDHB), 1p31 (dihydrolipoamide branched-chain transacylase E2 ), and 7q31-q32 (dihydrolipoamide dehydrogenase ), respectively. PATHOGENESIS - MSUD is caused by pathogenic variants of genes that encode branched-chain alpha-ketoacid dehydrogenase complex (BCKDC) components E1-alpha, E1-beta, E2, and E3. The MSUD incidence is up to 1:200 live births in certain Mennonite populations in Pennsylvania and elsewhere due to a founder variant (c.1312T>A) in the branched-chain ketoacid dehydrogenase complex gene ( BCKDHA). (See 'Inborn errors of metabolism: Classification'.)ĮPIDEMIOLOGY - MSUD occurs in approximately 1 in 86,800 to 185,000 live births. A general discussion of amino acid disorders is presented separately. It is characterized by psychomotor delay, feeding problems, and a maple syrup odor of the urine. It is caused by a deficiency of branched-chain alpha-ketoacid dehydrogenase complex (BCKDC), the second enzyme of the metabolic pathway of the three BCAAs, leucine, isoleucine, and valine. INTRODUCTION - Maple syrup urine disease (MSUD MIM #248600) also known as branched-chain ketoaciduria, is a disorder affecting the aliphatic or branched-chain amino acids (BCAAs).

Maple syrup urine disease symptoms in adults