Name short: GA-1

Name long: Glutaric acidemia type I

Description: People with this disorder have inadequate levels of an enzyme that helps break down the amino acids lysine, hydroxylysine, and tryptophan, which are building blocks of protein. Excessive levels of these amino acids and their intermediate breakdown products can accumulate and cause damage to the brain, particularly the basal ganglia, which are regions that help control movement. Intellectual disability may also occur. Some babies with glutaric acidemia type I are born with unusually large heads (macrocephaly). Affected individuals may have difficulty moving and may experience spasms, jerking, rigidity, or decreased muscle tone. Some individuals with glutaric acidemia have developed bleeding in the brain or eyes that could be mistaken for the effects of child abuse. Strict dietary control may help limit progression of the neurological damage. Stress caused by infection, fever or other demands on the body may lead to worsening of the signs and symptoms, with only partial recovery.

Incidence in the US 2001-2010: 265 in 24.5 million screens (10 cases per million).

Implicated genes:
Glutaryl-Coenzyme A dehydrogenase, GCDH


Variants in GCDH (see gnomAD page):
total variable positions: 584
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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