Name short: MSUD

Name long: Maple syrup urine disease

Description: Maple syrup urine disease (MSUD) can be caused by homozygous or compound heterozygous mutation in at least 3 genes: BCKDHA on chromosome 19q13, BCKDHB on chromosome 6q14, and DBT on chromosome 1p21. These genes encode 2 of the catalytic components of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), which catalyzes the catabolism of the branched-chain amino acids, leucine, isoleucine, and valine. The major clinical features of maple syrup urine disease are mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids are present in the urine, resulting from a block in oxidative decarboxylation.

Incidence in the US 2001-2010: 158 in 31.2 million screens (5 cases per million).

Implicated genes:
Dihydrolipoamide branched chain transacylase (E2 component of branched chain keto acid dehydrogenase complex), DBT
Branched chain keto acid dehydrogenase E1, beta polypeptide, BCKDHB
Branched chain keto acid dehydrogenase E1, alpha polypeptide, BCKDHA


Variants in DBT (see gnomAD page):
total variable positions: 326
rare variants: 0
common variants: 0
Allele frequency of rare (<0.001) variants and the implied number of homozygotes and compound heterozygotes, per million births (under the naive assumption that gnomAD captures all variants present in the human population; PSC = premature stop codon):

Population All rare variants Rare, resulting in PSC Rare, not intronic and not silent Known disease related All presumably detrimental
all 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
afr 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
amr 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
asj 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
eas 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
fin 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
nfe 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
oth 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
sas 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0


Expected number of homozygotes/compound heterozygotes in a demographic profile close to the US, using all known (as in, listed in gnomAD) rare nontrivial variants as causative variants: 0.

Expected number of homozygotes/compound heterozygotes in a demographic profile close to the US, using all presumably harmful variants as causative variants: 0.

Enzyme structure. Representative chain shown as white cartoon, with positions of known mutations shown as red sticks. Blue: physiological ions. Pink: substrates and cofactors.



Variants in BCKDHB (see gnomAD page):
total variable positions: 324
rare variants: 0
common variants: 0
Allele frequency of rare (<0.001) variants and the implied number of homozygotes and compound heterozygotes, per million births (under the naive assumption that gnomAD captures all variants present in the human population; PSC = premature stop codon):
Population All rare variants Rare, resulting in PSC Rare, not intronic and not silent Known disease related All presumably detrimental
all 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
afr 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
amr 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
asj 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
eas 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
fin 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
nfe 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
oth 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
sas 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0


Expected number of homozygotes/compound heterozygotes in a demographic profile close to the US, using all known (as in, listed in gnomAD) rare nontrivial variants as causative variants: 0.

Expected number of homozygotes/compound heterozygotes in a demographic profile close to the US, using all presumably harmful variants as causative variants: 0.

Enzyme structure. Representative chain shown as white cartoon, with positions of known mutations shown as red sticks. Blue: physiological ions. Pink: substrates and cofactors.



Variants in BCKDHA (see gnomAD page):
total variable positions: 818
rare variants: 0
common variants: 0
Allele frequency of rare (<0.001) variants and the implied number of homozygotes and compound heterozygotes, per million births (under the naive assumption that gnomAD captures all variants present in the human population; PSC = premature stop codon):
Population All rare variants Rare, resulting in PSC Rare, not intronic and not silent Known disease related All presumably detrimental
all 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
afr 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
amr 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
asj 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
eas 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
fin 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
nfe 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
oth 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0
sas 0 => 0 0 => 0 0 => 0 0 => 0 0 => 0


Expected number of homozygotes/compound heterozygotes in a demographic profile close to the US, using all known (as in, listed in gnomAD) rare nontrivial variants as causative variants: 0.

Expected number of homozygotes/compound heterozygotes in a demographic profile close to the US, using all presumably harmful variants as causative variants: 0.

Enzyme structure. Representative chain shown as white cartoon, with positions of known mutations shown as red sticks. Blue: physiological ions. Pink: substrates and cofactors.



Total estimated number of casses per million (all presumably harmful variants): 0.

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