New disease gene in paediatric heart disease

In studying children with severe early-onset cardiomyopathy, scientists have found that a hereditary mutation in the gene ‘alpha-kinase 3’ (ALPK3) can be a major culprit. In cases where both parents carry the mutation, the risk of having a child with severe cardiomyopathy is 25 percent. The condition typically develops at an early age since the child does not carry a normal copy of the gene, reported Medical News Today (MNT).

According to the National Heart, Lung and Blood Institute, cardiomyopathy causes the heart muscle to become enlarged, thick, or rigid and in rare cases, the muscle tissue in the heart can turn to scar tissue. Over time, the heart weakens and has difficulty pumping blood through the body or maintaining a normal electrical rhythm, leading to heart failure or arrhythmias (irregular heartbeats). 

Cardiomyopathy can either be inherited or acquired, meaning that it can manifest due to genes or to other factors. Since 40 percent of children born with cardiomyopathy die within five years of birth, discovery of its genetic basis is a significant finding, reports MNT.

"The identification of these mutations enables us to provide genetic counselling, predictive testing of family members, and prenatal testing in future pregnancies. It also allows us to provide early treatment, and a potential target for drug development in the future,” said Dr Johanna Herkert, clinical geneticist at the University Medical Centre of Groningen.

The ALPK3 gene is also thought to be involved in the milder, adult-onset form of the disease. “Several family members who carried only one mutated gene copy also developed cardiac disease, albeit at a later stage in life," said Dr Herkert.

"We knew that mice without a functional ALPK3 gene displayed very similar cardiomyopathy-related features to those observed in our paediatric patients," he said, "but we did not quite know how dramatic its effect would be in humans. Our findings show that we now should include this gene in routine diagnostic screening in order to be able to identify affected children and their family members at risk. This will also give us an insight into the prevalence of ALPK3-related cardiomyopathy in the general population."

Discovery of the ALPK3 gene and how it works also opens the potential for developing targeted drugs that can be administered immediately after birth, before the disease becomes severe. "Better knowledge of the precise role of the gene in disease development, as well as the elucidation of the molecular pathways involved, should lead us towards improved clinical care from the point of view of screening and surveillance, and to targeted drug development," Dr Herkert told MNT.