Glutaric Acidemia type 1
Glutaric acidemia type 1 (GA-1) is one of the treatable autosomal recessively inherited metabolic disorders. The pathology is mainly characterized by organic brain aciduria caused by deficiency of the enzyme glutaryl-CoA dehydrogenase. Recently, however, it has been observed that, with the course of the disease, it can affect the peripheral nervous system and the kidneys.
The worldwide prevalence of GA-1 is estimated to be 1 in 100,000 people and its incidence is 1 case in 40,000 births. GA-1 may be more prevalent in certain population groups (up to 1:250) in which consanguinity relationships exist such as the Amish community, Oji-Cree Native Canadians, Irish Travellers, Lumbee Native Americans and the South African Xhosa population.
Early detection of metabolites, such as glutarylcarnitine or C5DC, by chromatography/mass spectrometry in conjunction with GCDH gene analysis may facilitate early diagnosis of GA-1.
Symptoms
The first symptoms usually manifest during infancy or even prenatally. Early symptoms usually appear between the ages of 3 months and three years and include:
- Progressive macrocephaly
- Hypotonia
- Loss of motor skills
- Difficulty feeding
- Seizures
There are cases in which the symptoms are more nonspecific and their onset is later, mainly affecting the nervous system (headaches, vertigo, dementia and ataxia). At older ages and with appropriate treatment, the risk of encephalopathic seizures decreases.
Prevention
Early detection in asymptomatic infants can help to initiate treatment as early as possible and thus reduce the risk of encephalopathic crises. Between 80 and 90% of newborn patients who are treated before symptoms appear remain asymptomatic throughout life. However, the risk of other manifestations resulting from treatment, e.g. renal dysfunction, should be assessed.
Daily management includes combined metabolic therapy, consisting of a low lysine diet, carnitine supplementation together with emergency treatment during any episode.
Genes analyzed
