Carbonic anhydrase VA deficiency ..., (Carbonic anhydrase deficiency VA) - Gen CA5A
Carbonic anhydrase deficiency VA, also known as CA-VA deficiency or deficiency hyperammonemia due to carbonic anhydrase VA, is an inherited disorder characterized by episodes of metabolic crisis and acute encephalopathy. These potentially fatal episodes can cause loss of appetite, vomiting, weight loss, lethargy, tachypnea, seizures or coma. During an episode, deficient individuals have carbonic anhydrase VA hyperammonemia, metabolic acidosis and respiratory alkalosis, hypoglycemia, and a reduction in bicarbonate production in the liver. These imbalances are responsible for the signs and symptoms that occur during episodes.
People with carbonic anhydrase deficiency VA suffer the first episodes of the disease around 2 years old. These episodes may be triggered by periods of fasting or periods when energy demands, such as increase during illness. Between episodes, affected children are generally healthy, and more than half have more episodes after the first. Some affected children show a slight developmental delay or learning, while other children are developing normally. It is believed that the risk of metabolic encephalopathy crisis and after infancy reduced.
This process is due to mutations in the gene CA5A (carbonic anhydrase 5A), located on the long arm of chromosome 16 (16q24.3), which encodes the enzyme carbonic anhydrase VA. This enzyme helps convert carbon dioxide into bicarbonate, needed to maintain the acid-base balance in the body, which is necessary for most biological reactions are carried out correctly. The enzyme carbonic anhydrase VA is particularly important in the liver, where necessary bicarbonate for four enzymes in mitochondria is provided: carbomoyl phosphate synthase-1, pyruvate carboxylase and propionyl CoA carboxylase 3-methylcrotonyl CoA carboxylase. These enzymes help regulate the levels of certain substances in the body: the phosphate synthetase carbomoyl-1 is involved in the urea cycle, which processes the excess nitrogen and prevents to accumulate as ammonia; pyruvate carboxylase is involved in gluconeogenesis in the liver; while propionyl-CoA carboxylase and 3-methylcrotonyl CoA carboxylase contribute to the breakdown of certain amino acids.
They have identified at least three CA5A gene mutations in people with carbonic anhydrase deficiency VA. Mutations in the gene result CA5A one enzyme carbonic anhydrase VA nonfunctional or altered function, which causes a reduction in the production of bicarbonate. Insufficient bicarbonate concentration in the body causes a deterioration in control of acid-base balance and reduces the activity of the four mitochondrial enzymes affected, resulting in various biochemical abnormalities associated with the disease and are the reason for the episodes that occur in people with carbonic anhydrase deficiency VA.
This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease. Some people who have two copies of the altered gene never develop the disease, a situation known as reduced penetrance. Studies indicate that if people with these mutations exceed the vulnerable period of childhood without having an episode of encephalopathy, may never manifest signs or symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated carbonic anhydrase condeficiencia VA, by the complete PCR amplification of exons CA5A gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).