SNP Shot: Genomic Insights

Dihydrolipoamide dehydrogenase deficiency is a serious disorder impacting multiple bodily functions. The condition's signs and symptoms typically manifest soon after birth, though their presentation can vary considerably from person to person.

A hallmark of this deficiency is lactic acidosis, a potentially fatal accumulation of lactic acid. This can lead to nausea, vomiting, significant respiratory distress, and an irregular heartbeat. Neurological issues are also frequently observed. Initial symptoms in infants often include reduced muscle tone (hypotonia) and extreme fatigue (lethargy). As the condition progresses, infants may struggle with feeding, exhibit decreased awareness, and experience seizures.

Liver complications are also possible, ranging from liver enlargement (hepatomegaly) to life-threatening liver failure. In some individuals, liver disease is the predominant symptom and can emerge at any time from infancy to adulthood. Liver issues are generally accompanied by recurring vomiting and abdominal discomfort. In rare cases, individuals with dihydrolipoamide dehydrogenase deficiency may experience muscle weakness in the skeletal muscles, particularly during physical activity; drooping eyelids; or a weakened heart muscle (cardiomyopathy). Additional characteristics of the condition can include elevated levels of ammonia in the blood (hyperammonemia), an accumulation of ketones (ketoacidosis), or low blood sugar (hypoglycemia).

The symptoms of dihydrolipoamide dehydrogenase deficiency commonly manifest in episodes triggered by fever, injury, or other physical stressors. Between episodes, affected individuals are generally asymptomatic. Due to the severity of these episodes, many infants with the condition do not survive past the first few years of life. Those who do survive beyond early childhood often experience developmental delays and neurological issues, such as intellectual disability, muscle stiffness (spasticity), impaired coordination (ataxia), and seizures.

Inheritance:

The inheritance pattern for this condition is autosomal recessive. This means that both copies of the relevant gene within each cell must contain mutations for the condition to manifest. The parents of an individual with an autosomal recessive disorder each carry a single copy of the mutated gene, but usually do not exhibit any signs or symptoms of the condition themselves.