Women with Fabry disease can suffer from significant disease that affects several organs, and should be closely monitored for possibly starting enzyme replacement therapy, recent research shows.
The study, “Major Organic Involvement in Women with Fabry Disease in Argentina,” was published in the Scientific World Journal.
Fabry disease is caused by a mutation in the GLA gene. This gene provides instructions to make an enzyme called α-galactosidase A (α-galA), which is responsible for the breakdown of complex molecules called glycosphingolipids.
Patients with Fabry disease have a deficient or null activity of the α-galA enzyme, resulting in the accumulation of glycosphingolipids across multiple organs. These deposits are known to trigger cell death, fibrosis (hardening) of the organ, and irreversible damage.
Fabry disease can involve major organs, including the cardiovascular system (heart), the renal system (kidneys) and the central nervous system (brain), among others. The manifestations of the disease follow different patterns in men and women.
The GLA gene is located on the X-chromosome. Males have only one X-chromosome, while females have two X-chromosomes. So, if a male inherits the mutated copy of the GLA gene, he does not have a second chromosome to compensate for the lack of α-galA. Women, however, are able to do so.
For this reason, women who inherit the α-galA mutation present with a range of severities. This is due to a genetic phenomenon called X-inactivation, whereby one of the two copies of the X-chromosome in females becomes inactivated. While some cells inactivate one of their X-chromosomes (potentially carrying the defective GLA gene), others inactivate the other copy.
Consequently, α-galA enzyme activity in women with Fabry disease usually is in the lower normal range, which requires genetic analysis to make a confirmed diagnosis.
A 2001 study showed that most women with Fabry disease were asymptomatic, had normal quality of life and only developed mild disease. However, since then, other studies have reported that women can develop severe symptoms with risk of premature death.
To determine which organs are affected in women at the time of diagnosis, researchers carried out a study and evaluated 35 women with Fabry disease at three different centers across Argentina.
Among the group, 22 patients were adult (older than 18) and 13 were pediatric patients. Enzymatic activity was evaluated in 29 participants and was found to be normal in 82.8% of them. Researchers identified seven different mutations in the GLA gene across all participants.
Almost half (45.7%) of the women had urinary protein loss and 31.4% showed reduced glomerular filtration rate, both signs associated with Fabry nephropathy (a type of renal disease), suggesting kidney involvement. These symptoms were observed mostly in adults, not children.
Additionally, 56.5% of patients developed cornea verticillata (a type of eye disease that affects the cornea), 51.4% developed peripheral neuropathy (damaged or diseased nerves), 20% had hearing loss, and 20% had angiokeratomas (a condition in which small, dark spots appear on the skin).
Seventeen percent developed issues of the central nervous system such as recurrent burning sensations in the extremities, 14.3% developed gastrointestinal issues, and 31.4% had cardiovascular complications such as left ventricular hypertrophy (enlargement and thickening of the walls of the heart’s main pumping chamber) or arrhythmia (irregular heartbeat).
These results suggest that women with Fabry disease experience disease manifestation across multiple organs, including the kidney, heart, brain, eyes, and skin.
“Women with FD suffer from significant multisystemic disease which can lead to deterioration in the quality of life and risk of premature death,” the authors wrote. “Females should be regularly monitored to determine the timing of enzyme replacement therapy initiation, which must be early without waiting for advanced organic compromise,” they concluded.