2-Methylbutyryl-CoA dehydrogenase deficiency

2-Methylbutyryl-CoA dehydrogenase deficiency
Classification and external resources
2-Methylbutyryl-CoA
OMIM	610006
DiseasesDB	34413

2-Methylbutyryl-CoA dehydrogenase deficiency, also called 2-Methylbutyryl glycinuria or short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD),^[1] is an autosomal recessive metabolic disorder.^[2] It causes the body to be unable to process the amino acid isoleucine properly. Initial case reports identified individuals with developmental delay and epilepsy, however most cases identified through newborn screening have been asymptomatic.

Signs and symptoms

SBCADD is included as a secondary target condition in most newborn screening programs, as the key analyte is the same as is used to identify isovaleric acidemia.^[3][4] Most cases have been Hmong individuals, who are asymptomatic.^[5] There are isolated case reports where individuals have been identified with SBCADD in addition to developmental delay and epilepsy. It is currently unclear what the complete clinical presentation of SBCADD looks like. There is some concern that these cases with additional symptoms may reflect an ascertainment bias rather than being a true representation of the clinical spectrum of the disease.^[1] Currently, there is no accepted treatment, as most affected individuals do not require any. Some recommend avoidance of valproic acid, as it can be a substrate for 2-methylbutyryl-CoA dehydrogenase.^[5]

Cause and genetics

The disorder is caused by a mutation in the ACADSB gene, located on the long arm of human chromosome 10 (10q25-q26).^[1][6] It is inherited in an autosomal recessive manner, which means an affected individual must inherit one copy of the mutation from each parent.^[2]

Diagnosis

Most individuals with SBCADD are identified through newborn screening, where they present with an elevation of a five carbon acylcarnitine species.^[1] Confirmatory testing includes plasma and urine analysis to identify the carnitine and glycine conjugates of 2-methylbutyryl-CoA.^[1]

References

v t e Inborn error of amino acid metabolism (E70–E72, 270) K→acetyl-CoA Lysine/straight chain Glutaric acidemia type 1 type 2 Hyperlysinemia Pipecolic acidemia Saccharopinuria Leucine 3-hydroxy-3-methylglutaryl-CoA lyase deficiency 3-Methylcrotonyl-CoA carboxylase deficiency 3-Methylglutaconic aciduria 1 Isovaleric acidemia Maple syrup urine disease Tryptophan Hypertryptophanemia G G→pyruvate→citrate Glycine D-Glyceric acidemia Glutathione synthetase deficiency Sarcosinemia Glycine→Creatine: GAMT deficiency Glycine encephalopathy G→glutamate→ α-ketoglutarate Histidine Carnosinemia Histidinemia Urocanic aciduria Proline Hyperprolinemia Prolidase deficiency Glutamate/glutamine SSADHD G→propionyl-CoA→ succinyl-CoA Valine Hypervalinemia Isobutyryl-CoA dehydrogenase deficiency Maple syrup urine disease Isoleucine 2-Methylbutyryl-CoA dehydrogenase deficiency Beta-ketothiolase deficiency Maple syrup urine disease Methionine Cystathioninuria Homocystinuria Hypermethioninemia General BC/OA Methylmalonic acidemia Methylmalonyl-CoA mutase deficiency Propionic acidemia G→fumarate Phenylalanine/tyrosine Phenylketonuria 6-Pyruvoyltetrahydropterin synthase deficiency Tetrahydrobiopterin deficiency Tyrosinemia Alkaptonuria/Ochronosis Type I tyrosinemia Type II tyrosinemia Type III tyrosinemia/Hawkinsinuria Tyrosine→Melanin Albinism: Ocular albinism (1) Oculocutaneous albinism (Hermansky–Pudlak syndrome) Waardenburg syndrome Tyrosine→Norepinephrine Dopamine beta hydroxylase deficiency reverse: Brunner syndrome G→oxaloacetate Urea cycle/Hyperammonemia (arginine aspartate) Argininemia Argininosuccinic aciduria Carbamoyl phosphate synthetase I deficiency Citrullinemia N-Acetylglutamate synthase deficiency Ornithine transcarbamylase deficiency/translocase deficiency Transport/ IE of RTT Solute carrier family: Cystinuria Hartnup disease Iminoglycinuria Lysinuric protein intolerance Fanconi syndrome: Oculocerebrorenal syndrome Cystinosis Other 2-Hydroxyglutaric aciduria Aminoacylase 1 deficiency Ethylmalonic encephalopathy Fumarase deficiency Trimethylaminuria M: MET mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)