SNP Shot: Genomic Insights

Carbonic anhydrase VA deficiency is a genetic condition where the body experiences periods of metabolic imbalance (metabolic crisis) and abnormal brain function (acute encephalopathy). These episodes can be life-threatening and may manifest as difficulty feeding, vomiting, weight loss, extreme tiredness (lethargy), rapid breathing (tachypnea), seizures, or even coma.

During these episodes, individuals with this deficiency experience elevated ammonia levels in the blood (hyperammonemia), disturbances in the blood's acid-base balance (metabolic acidosis and respiratory alkalosis), low blood sugar (hypoglycemia), and decreased bicarbonate production in the liver. These biochemical imbalances cause the observed signs and symptoms.

The initial episodes of carbonic anhydrase VA deficiency usually occur before the age of 2. These episodes can be triggered by prolonged periods without food (fasting) or during times of increased energy needs, such as during illnesses. Between episodes, affected children are usually healthy, and over half do not experience further episodes after their first. While some affected children may have slight developmental delays or learning difficulties, others develop at a normal pace.

The likelihood of experiencing metabolic crisis and acute encephalopathy is believed to lessen after childhood. Due to the rarity of this condition and the limited number of diagnosed cases, the long-term effects of carbonic anhydrase VA deficiency in adulthood remain unclear.

Inheritance:

This condition follows an autosomal recessive inheritance pattern. This means that an individual must inherit a mutated copy of the responsible gene from both parents to be affected. The parents, who each carry only one copy of the mutated gene, are typically asymptomatic. In some cases, individuals inheriting two copies of the altered gene may not develop the condition, a phenomenon known as reduced penetrance. Researchers believe that if individuals with these mutations successfully navigate childhood without experiencing an encephalopathic episode, they may remain asymptomatic throughout their lives.