Carbonic Anhydrase 5a Deficiency

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This is a rare disorder caused by a fault in the CA5A gene which provides instructions to make an enzyme called carbonic anhydrase 5a. Your body needs the enzyme to convert carbon dioxide to bicarbonate. Bicarbonate ensures a controlled acid balance in the body. This is important to maintain an environment where chemical reactions can take place. The enzyme is particularly important in the liver where bicarbonate is used by four other enzymes which play key roles in the body’s metabolism such as energy production, the removal of ammonia which can become toxic, and the break-down of proteins to produce certain amino acids. A fault in the CA5A gene means that not enough enzyme is produced, and this reduces the activity of the enzymes in the liver as well as causing several metabolic abnormalities. The imbalance causes the acute onset of symptoms affecting the brain and the other signs and symptoms of this disorder.

We do not know the exact prevalence of this disorder. It is believed that the disorder may often be misdiagnosed.

This disorder is characterised by episodes of metabolic crisis, often first experienced before the age of 2 years. A metabolic crisis occurs when different substances build up becoming toxic. If left untreated they can cause damage to the brain and become life-threatening. They can be triggered by long periods without food, illness or infection, or other factors which increase metabolic stress. In this disorder, these crises are characterised by:

• High levels of ammonia in the blood (hyperammonaemia)
• An imbalance of acids in the blood (metabolic acidosis and respiratory alkalosis)
• Low blood sugar levels (hypoglycaemia)
• Reduced production of bicarbonate in the liver.Symptoms of a metabolic crisis include:
• Lethargy
• Poor feeding
• Weight loss
• Irregular breathing
• Irritability
• Seizures
• Coma

In some cases, children may have learning disabilities or a delay in reaching some developmental milestones. However, in general most people are healthy in between crises and approximately half of people do not experience any further episodes after their first. The risk of having a metabolic crisis is thought to decrease after childhood.

This disorder is most often recognised following the onset of the first metabolic crisis through blood and urine tests. The disorder will need to distinguish from the urea cycle disorders, organic acidurias, and Pyruvate carboxylase deficiency. Diagnosis is confirmed after finding the mutation in the CA5A gene.

During any illness, an emergency regimen is given. This will reduce the build-up of toxic substances and includes a high-calorie, lipid-rich formula which is restricted in protein but normal in carbohydrates. In some cases, carglumic acid may be given to assist in the treatment of high ammonia levels (hyperammonaemia). Other treatment is symptomatic and supportive.

Humans have chromosomes composed of DNA. Genes are pieces of DNA that carry the genetic instruction. Each chromosome may have several thousand genes. The word mutation means a change or error in the genetic instruction. We inherit particular chromosomes from the egg of the mother and sperm of the father. The genes on those chromosomes carry the instruction that determines characteristics, which are a combination of the parents.

This is an inherited disorder. There is nothing that could have been done to prevent you/your child from having this disorder.

Everyone has a pair of genes that make the Carbonic Anhydrase 5a enzyme. In people with this disorder, neither of these genes works correctly. One non-working gene is inherited from each parent.

Parents of those with Carbonic Anhydrase 5a Deficiency are carriers of the disorder. Carriers do not have the disorder because the other gene of this pair is working correctly.

When both parents are carriers, in each pregnancy the risk to the baby is as follows:

• 25% chance (1 in 4) of having the disorder.

• 50% chance (1 in 2) for the baby to be a carrier.

• 25% chance (1 in 4) for the baby to have two working genes and neither have the disorder nor be a carrier

References are available on request. Please email contact@metabolicsupportuk.org or call 0845 241 2173  [Resource Library No: CAP013].