GCDH gene
Also known as: Glutaric aciduria, type I; Glutaryl-CoA Dehidrogenase Deficiency; GA1.
OMIM#231670 https://omim.org/entry/231670
1. The disease:
Glutaryl-CoA dehydrogenase (GCDH) deficiency (GDD) is an autosomal recessive neurometabolic disorder clinically characterized by encephalopathic crises resulting in striatal injury and a severe dystonic dyskinetic movement disorder. Lack of early signs or symptoms does not exclude the diagnosis.
2. The Symptoms:
Neonates are mainly asymptomatic, although 75% present with macrocephaly and possibly show hypotonia and irritability. If undiagnosed, the initial acute encephalopathic crisis occurs between 3-36 months, typically precipitated by an intercurrent febrile illness, vaccination or a surgical intervention, and characterized by hypotonia, loss of motor skills and convulsions resulting in bilateral striatal injury with severe secondary dystonia and occasionally subdural and retinal hemorrhage. GDD can exceptionally present with hypoglycemia or acidosis. With age (>6 years) and with appropriate treatment, the risk of encephalopathic crises subsides. In some patients, hypotonia and dystonia develop gradually with no encephalopathic crisis, which is known as late-onset or insidious-onset GDD.
3. Actions to take in case of early diagnosis:
- Infants with a positive genetic test (having 2 pathogenic variants or 2 copies of a single pathogenic variant in the gene GCDH) should continue breastfeeding and avoid baby formulas. Early treatment is essential in preventing chronic symptoms.
- Biochemical correlation is essential for confirming diagnosis with biochemical NBS with tandem mass spectrometry (high glutarylcarnitine – C5DC) and urinary organic acids for accumulation of glutaric acid (GA), 3-hydroxyglutaric (3-OH-GA) and glutaconic acids.
- GA1 is a lifelong disease that requires lifetime management and regular follow-up with a metabolic physician and dietician, a part from a multidisciplinary approach to care.
- Daily management comprises a low lysine diet with metabolic specific formula, carnitine supplementation in association with prompt emergency treatment during intercurrent illness. During acute episodes, management includes, most importantly, increasing energy supply (20-100 % above RDI); omission of natural protein for 24-48 hours followed by a gradual reintroduction; L-carnitine supplementation doubling and close monitoring of glucose, electrolyte and fluid balance, as well as urea and liver status by an informed skilled interdisciplinary team. Adherence to emergency treatment recommendations is imperative in preventing neuronal damage and subsequent secondary dystonia.
- Genetic counseling is highly recommended for family planning and evaluation of at-risk family members such as siblings.
4. For more information
iblio: https://www.ncbi.nlm.nih.gov/books/NBK546575/