Details of Disease

General Information of Disease (ID: DIS61XRH)

• Disease Name: Maple syrup urine disease
• Synonyms: maple syrup urine disease, intermittent; branched-chain Alpha-Keto acid dehydrogenase deficiency; maple syrup urine disease, Intermediate; maple syrup urine disease, classic; Keto acid decarboxylase deficiency; dihydrolipoamide dehydrogenase deficiency; maple syrup urine disease, thiamine-responsive; maple syrup urine disease, type 1A; maple syrup urine disease, type 2; maple syrup urine disease, type 1B; Ketoacidaemia; branched-chain ketoaciduria; BCKDH deficiency; maple syrup urine disease; BCKD deficiency; branched-chain 2-ketoacid dehydrogenase deficiency; branched chain ketoaciduria; MSUD
• Definition: An autosomal recessive inherited disorder caused by mutations in the BCKDHA, BCKDHB, DBT, and DLD genes. It is characterized by a deficiency of branched-chain alpha-keto acid dehydrogenase complex, leading to accumulation of metabolites in the body fluids. The name of the disease derives from the sweet odor of the urine in infants, reminiscent of maple syrup. Signs and symptoms usually appear in infancy and include lethargy and developmental delays. If untreated, it may lead to seizures, coma, and death.|Editor note: genetic subtypes rolled into one OMIM entry. GARD treats as distinct
• Disease Hierarchy:
  DISB7ID3: Inborn organic aciduria
  DISOGOR1: Inborn disorder of branched-chain amino acid metabolism
  DIS61XRH: Maple syrup urine disease
• Disease Identifiers:
  MONDO ID: MONDO_0009563
  MESH ID: D008375
  UMLS CUI: C0024776
  OMIM ID: 248600
  MedGen ID: 6217
  Orphanet ID: 511
  SNOMED CT ID: 27718001

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 2 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
BCAT2	TTF9OQ6	Strong	Biomarker	[1]
CACNA2D2	TTU8P3M	Strong	Biomarker	[2]

This Disease Is Related to 10 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ARID4B	OTYLPILE	Strong	Biomarker	[3]
GPR4	OTIBF32I	Strong	Biomarker	[4]
MEA1	OT72PHSG	Strong	Biomarker	[5]
MKRN3	OTAFO4YR	Strong	Genetic Variation	[6]
PPM1K	OTNZ4N4E	Strong	Genetic Variation	[7]
TNS3	OTPG2D8Z	Strong	Biomarker	[8]
BCKDHA	OT0LHOZB	Definitive	Autosomal recessive	[9]
BCKDHB	OT8OSVYU	Definitive	Autosomal recessive	[10]
DBT	OT4KZ5R9	Definitive	Autosomal recessive	[11]
DLD	OT378CU9	Definitive	Autosomal recessive	[12]

References

• [1] Expanding the genetic and phenotypic spectrum of branched-chain amino acid transferase 2 deficiency.J Inherit Metab Dis. 2019 Sep;42(5):809-817. doi: 10.1002/jimd.12135. Epub 2019 Aug 1.
• [2] Discovery of Biomarker Panels for Neural Dysfunction in Inborn Errors of Amino Acid Metabolism.Sci Rep. 2019 Jun 24;9(1):9128. doi: 10.1038/s41598-019-45674-2.
• [3] Case report: maple syrup urine disease with a novel DBT gene mutation.BMC Pediatr. 2019 Dec 13;19(1):494. doi: 10.1186/s12887-019-1880-1.
• [4] Genome-wide screening identifies novel genes implicated in cellular sensitivity to BRAF(V600E) expression.Oncogene. 2020 Jan;39(4):723-738. doi: 10.1038/s41388-019-1022-0. Epub 2019 Sep 23.
• [5] Maple syrup urine disease hair reveals the importance of 18-methyleicosanoic acid in cuticular delamination.Micron. 2005;36(3):261-6. doi: 10.1016/j.micron.2004.11.004. Epub 2005 Jan 25.
• [6] Application of droplet digital PCR in the analysis of genome integration and organization of the transgene in BAC transgenic mice.Sci Rep. 2018 Apr 27;8(1):6638. doi: 10.1038/s41598-018-25001-x.
• [7] A novel regulatory defect in the branched-chain -keto acid dehydrogenase complex due to a mutation in the PPM1K gene causes a mild variant phenotype of maple syrup urine disease. Hum Mutat. 2013 Feb;34(2):355-62. doi: 10.1002/humu.22242. Epub 2012 Dec 12.
• [8] Heterogeneity in maple syrup urine disease: aspects of cofactor requirement and complementation in cultured fibroblasts.Clin Genet. 1977 Apr;11(4):277-84. doi: 10.1111/j.1399-0004.1977.tb01313.x.
• [9] Molecular genetic basis of maple syrup urine disease in a family with two defective alleles for branched chain acyltransferase and localization of the gene to human chromosome 1. Am J Hum Genet. 1991 Feb;48(2):342-50.
• [10] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
• [11] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [12] Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency. Hum Mol Genet. 1996 Dec;5(12):1925-30. doi: 10.1093/hmg/5.12.1925.