Finnish Researchers Discover New Gene Mutation Linked with Fabry Cardiomyopathy

Feb 17, 2020 | Cardiovascular, Fabry Cardiomyopathy, Finland, Genetics, Kuopio University Hospital, University of Eastern Finland

Finnish Researchers Discover New Gene Mutation Linked with Fabry Cardiomyopathy

Researchers from Finland have revealed in a study that the A143T variant of the GLA gene is associated with an increased risk of Fabry cardiomyopathy. The variant plays a role in lipid metabolism. The researchers reported that patients carrying the mutation and manifesting changes in the heart should initiate treatment to prevent the disease from progressing. The study was led by investigators from both University of Eastern Finland and Kuopio University Hospital. 

Recently published in the journal Heart, this most recent research was inspired by actual patient engagement in the clinic, reported Johanna Kuusisto from the University of Eastern Finland.

What is Fabry Cardiomyopathy?

A rare disease of the lipid metabolism where α-galactosidase A, i.e. the GLA enzyme, is missing or is functionally deficient due to a gene mutation. Fabry cardiomyopathy leads to the accumulation of harmful lipids on blood vessel walls, the heart, the kidneys, and the nervous system. More than 900 mutations of the GLA gene associated with this disease are known to date. Symptoms caused by this condition vary in terms of severity. In the classical and most severe from, GLA enzyme activity is fully or almost fully non-existent, and symptoms begin already in childhood.  Typically, men, with severe symptoms including pain, sweating disorders and gastrointestinal problems, develop a severe multisystem disease prior to middle age. Women and men carrying a less severe mutation have some GLA enzyme activity, and do not become symptomatic until adulthood. With this form of the disease, lipid usually accumulates only in the heart. The heart muscle thickens and starts to be replaced by connective tissue. Patients suffer from shortness of breath, chest pain, arrhythmia, and they need a pacemaker due to conduction disorders.  This can lead to heart failure which is the most common cause of death with Fabry cardiomyopathy.

Diagnosing the Disease

Ultrasound and magnetic imaging of the heart is a key diagnostic role. Fabry cardiomyopathy is confirmed by genetic testing and by analyzing GLA enzyme activity from a blood sample. In unclear cases, heart and kidney biopsy is used to confirm lipid accumulation.

Options and Risk

In some cases, progression can be prevented by intravenous enzyme replacement therapy, and in carriers of some specific mutations, by orally administered drugs. Timely treatment may reduce the accumulation of harmful lipids.  Untreated Fabry cardiomyopathy deteriorates the quality of life and predisposes to premature death. Even patients with minor symptoms can be at risk of a sudden death, a Fabry cardiomyopathy is associated with the risk of arrhythmia.

Cases in Finland

Presently over 100 people in Finland have been diagnosed with the disease or as asymptomatic carriers of the GLA mutation, and 19 of these individuals are form Kuopio University Hospital’s catchment area. The research and care team are monitoring 13 patients while eight of them have received enzyme replacement therapy.


The Finish researchers newly published study analyzed cardiomyopathy-associated gene mutations, including the variant A143T of the GLA gene, in altogether 11 members of the same family. The researchers observed and examined these carriers of this variant via laboratory tests and CMR and PET-CT imaging, and heart biopsies were collected from two patients with history of heart symptoms.

Professor Johanna Kuusisto noted that the study “shows that the A143T variant, a mutation of the GLA gene, is likely to cause late-onset Fabry cardiomyopathy. It is important to initiate enzyme replacement therapy in patients who are carriers of this mutation and who manifest changes in their heat. In addition, their family members who also are carriers of this mutation should be monitored for Fabry cardiomyopathy.”

Lead Research/Investigator

Professor Johanna Kuusisto 

Source: EurekAlert!


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