BabyScreen+ newborn screening

Gene: GCDH

Green List (high evidence)

Well established gene-disease association.

Typically presents in infancy, though later presentations also reported.
In neonates and infants, unspecific neurologic symptoms such as muscular hypotonia and delayed motor development occur in about half of all individuals with GA-I, the remaining individuals are asymptomatic. Macrocephaly occurs in approximately 75% of individuals. Untreated, 80-90% of infants will develop neurologic disease during brain development (mainly between 3 and 36 months) following an acute encephalopathic crisis precipitated by illness, vaccination, or surgical intervention. These crises characteristically result in the gradual development of complex movement disorders in the following months and years. Dystonia at rest with action-induced exacerbation, which profoundly interferes with any voluntary movement, is often incapacitating. Dysarthria and dysphagia are also common. Cognitive function in generally considered to be preserved; however comprehensive studies on cognitive functions in GA-I have not been reported. Given the characteristic cerebral abnormalities frequently observed in GA-I and the impact of similar white matter changes observed in other neurologic diseases, individuals with GA-I might be at risk for cognitive dysfunction. In approximately 10-20% of individuals with “insidious onset” type, neurologic disease and striatal injury occur in the absence of encephalopathic crises.

Treatment: avoid fasting, carnitine, protein restricted diet, restrict lysine, hydroxylysine, and tryptophan

Non-genetic confirmatory testing: urine organic acids, leukocyte enzyme activity

Created: 29 Sep 2022, 7:27 a.m. | Last Modified: 29 Sep 2022, 7:27 a.m.

Panel Version: 0.270

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Glutaric aciduria, type I MIM#231670

Publications

• 33069577

Green List (high evidence)

is on the current VCGS newborn screening panel

Created: 26 Sep 2022, 2:13 a.m. | Last Modified: 26 Sep 2022, 2:13 a.m.

Panel Version: 0.199

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal