Nav: Home

New gene mutation associated with Fabry cardiomyopathy

February 13, 2020

The A143T variant of the GLA gene is associated with an increased risk of Fabry cardiomyopathy, according to a new study. The variant plays a role in lipid metabolism. According to the researchers, patients carrying the mutation and manifesting changes in the heart should initiate treatment to prevent the disease from progressing. The study, conducted at the University of Eastern Finland and Kuopio University Hospital, was published in the journal Heart.

However, not all carriers of the mutation develop Fabry cardiomyopathy, and the association of the A143T variant with the disease is not fully understood yet.

According to Professor Johanna Kuusisto from the University of Eastern Finland, the study was inspired by clinical work with patients.

"We had to consider the feasibility of initiating expensive enzyme replacement therapy when Cardiologist Kati Valtola discovered a cardiomyopathy in three members of the same family. Genetic testing revealed that they all carried the A143T variant, whose role in the pathogenesis of Fabry cardiomyopathy has been previously questioned," Professor Kuusisto says.

Fabry cardiomyopathy is 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. It 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 that are associated with Fabry cardiomyopathy are known to date. The symptoms caused by these mutations vary greatly in terms of their severity. In the classical and most severe form, GLA enzyme activity is fully or almost fully non-existent, and symptoms begin already in childhood. Patients are usually men and their symptoms are severe, including pain, sweating disorders and gastrointestinal problems. Typically, they develop a severe multisystem disease before reaching middle age. Women and men carrying a less severe mutation have some GLA enzyme activity, and they do not become symptomatic until adulthood. In 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 and arrhythmia, and they may need a pacemaker due to conduction disorders. Cardiomyopathy may lead to heart failure, which is the most common cause of death in people with Fabry cardiomyopathy.

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

Asymptomatic carriers should be monitored, too

The progression of Fabry cardiomyopathy can be prevented by intravenous enzyme replacement therapy and, in carriers of some specific mutations, by orally administered drugs. Timely treatment can 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, as Fabry cardiomyopathy is associated with the risk of arrhythmia.

In Finland, more than 100 people so far have been diagnosed with Fabry cardiomyopathy or as asymptomatic carriers of the GLA mutation, and 19 of these individuals are from Kuopio University Hospital's catchment area.

"We are currently monitoring 13 patients of whom eight receive enzyme replacement therapy," Kuusisto says.

The newly published study analysed cardiomyopathy-associated gene mutations, including the variant A143T of the GLA gene, in altogether 11 members of the same family. The carriers of this variant were carefully examined using, e.g., laboratory tests and CMR and PET-CT imaging, and heart biopsies were taken from two patients with a history of heart symptoms.

Professor Kuusisto says that it wasn't clear in the beginning of the study whether the variant in question causes Fabry disease, or whether it is just a harmless mutation.

"Our study now 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," Professor Kuusisto points out.
-end-
For further information, please contact: Professor Johanna Kuusisto, johanna.kuusisto (a) kuh.fi, tel. +358 17 173949

Research article: Valtola K, Nino-Quintero J, Hedman M, Lottonen-Raikaslehto L, Laitinen T, Maria M, Kantola I, Naukkarinen A, Laakso M, Kuusisto J. Cardiomyopathy associated with the Ala143Thr variant of the α-galactosidase A gene. Heart, 2020;0:1-7. doi:10.1136/heartjnl-2019-315933

University of Eastern Finland

Related Genetic Testing Articles:

For acute myeloid leukemia, genetic testing is often worth the wait
New tailored therapies offer exciting prospects for treating acute myeloid leukemia (AML), but taking advantage of them may require waiting a week or more for genetic testing before starting treatment, posing a dilemma for doctors and patients facing this deadly and often fast-moving disease.
Genetic testing among individuals with ASD
Professional medical societies recommend certain genetic tests for individuals with autism spectrum disorder (ASD).
Breast cancer patients to be evaluated for genetic testing
The guidance from the ACMG differs from a consensus guideline issued in February by the American Society of Breast Surgeons, which recommended genetic testing for all newly diagnosed patients with breast cancer.
New technique isolates placental cells for non-invasive genetic testing
A new technique for isolating cells carrying the full fetal genome from cervical swabs could enable doctors to diagnose genetic disorders without using needles to harvest cells from the placenta.
BRCA1/2 genetic testing recommendations still leave issues unresolved
The U.S. Preventive Services Task Force offers new guidelines on BRCA1/2 genetic testing.
Does genetic testing pose psychosocial risks?
For the last quarter century, researchers have been asking whether genetic information might have negative psychosocial effects.
Genetic testing has a data problem; New software can help
As at-home genetic testing becomes more popular, companies are grappling with how to store all the accumulating data and how to process results quickly.
Genetic testing gives answers on developmental disorders during pregnancy
Genetic testing improves diagnoses of abnormalities in developing babies picked up during ultrasound scans, scientists report today in The Lancet.
In prenatal testing, 'genomics' sometimes sees what genetic tests can't
One of the first large prospective studies of its kind reveals the potential -- and limitations -- of a new form of genetic testing in pregnancy.
Genetic testing does not cause undue worry for breast cancer patients
As genetic testing for breast cancer has become more complex, evaluating a panel of multiple genes, it introduces more uncertainty about the results.
More Genetic Testing News and Genetic Testing Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Making Amends
What makes a true apology? What does it mean to make amends for past mistakes? This hour, TED speakers explore how repairing the wrongs of the past is the first step toward healing for the future. Guests include historian and preservationist Brent Leggs, law professor Martha Minow, librarian Dawn Wacek, and playwright V (formerly Eve Ensler).
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.