HADHA gene mutations: a preconception test to identify risk

You and your partner are thinking about having a child but are concerned about possible genetic diseases the baby might have? A state-of-the-art preconception test lets you know the Risk of transmitting genetic disease to the child even before conception occurs.

Knowing one’s genetic predisposition

Know your own genetic predisposition is essential as many heritable genetic diseases are severe and disabling. These disorders occur when one or more genes in the DNA are mutated. If the disease is recessive, Occurs when both parents carry recessive mutations of the same gene and pass the mutated genes on to their offspring.

In these cases, the child’s chance of manifesting the disease is 25 percent. 1

An example of a recessively transmitted disease is the long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). LCHADD is caused by a mutation in the gene HADHA, which produces an enzyme that, when mutated, results in a Deficiency in conversion of fatty acids to energy. 2 The disease has an incidence of 1:250.000 and is the second most common fatty acid oxidation deficiency (the first involves medium-chain fatty acids). 3,5

Fatty acids are an important energy resource

Fatty acids are an important energy resource, second only to sugars. When fasting for many hours, or in cases of intense exercise, fatty acids are catabolized for energy production. To fully catabolize a long-chain fatty acid, that is, to reduce it to the smallest components that a cell can use to derive energy, multiple enzymes are required, including the 3-Hydroxyacyl-CoA dehydrogenase.

In the case where this enzyme is mutated, the body is unable to complete all the steps of catabolism and convert fatty acids into energy for cells and tissues. 2,3

Very severe symptoms as early as birth

Clinically, most patients with LCHADD have the following Very severe symptoms since birth, or otherwise occur in the first few months of life. Disease causes hypoglycemia, metabolic acidosis, hypotonia, rhabdomyolysis, cardiomyopathy and arrhythmia, peripheral neuropathy, and liver abnormalities. 2,5

The therapy Includes several strategies to block the acute stages or to improve the long-term effects. During acute manifestations, glucose is administered and attempts are made to hydrate the patient as much as possible. In the long term, a diet high in carbohydrates and medium-chain triglycerides is put in place, while prolonged fasting and intense physical exertion are recommended to be avoided. 5

LCHADD has no particular symptoms for which diagnosis requires multiple tests: 4

• evaluation of metabolites in the blood and urine in the acute stages of symptom manifestation is carried out;
• the patient is tested by fasting, possibly in combination with an oral fatty acid load;
• an enzyme assay is performed, which is essential for diagnostic confirmation of the various biochemical defects;
• Molecular genetic tests that can identify the presence of specific mutations 4 .

Given the severity of this and other recessive genetic disorders, it is important to know one’s reproductive risk. This can be done by undergoing a preconception genetic testing, as the Igea tests: is done through a blood draw from both prospective parents, and the result will indicate whether you carry any genetic disorder that can be transmitted to your offspring, such as long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.

You consult your doctor to plan a suitable and safe reproductive pathway. Also, learn more about transmissible mutations detectable with Igea by visiting: www.sorgentegenetics.en

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