Fabry disease in Ostrobothnia and across Finland: FAST and FinFabry Studies

Fabry disease (FD) is a rare, X‑linked lysosomal storage disorder in which a mutation in the GLA gene causes deficiency of the enzyme α‑galactosidase A (αGAL A). This leads to the accumulation of sphingolipids and progressive damage, especially in the heart, brain, and kidneys, shortening life expectancy. Cardiac involvement is the most common cause of death. Treatment consists of intravenous enzyme replacement therapy (ERT) or oral migalastat, which stabilises the enzyme’s structure. More than 1,000 GLA variants are known. In the most severe form, αGAL A activity is nearly absent. Disease severity varies, but men are generally more severely affected. In Ostrobothnia, the classical FD‑causing Arg227Ter variant is found. It results in a truncated enzyme and zero αGAL A activity in males. The Fabry disease single mutation follow-up study in Ostrobothnia (the FAST study) followed Arg227Ter patients before and during ERT. The first publication confirmed that the Arg227Ter variant is highly pathogenic in both sexes. The second publication showed that lung involvement was mild and slowly progressive in non‑smokers. The third publication examined disease progression in major target organs: FD progressed in some patients despite ERT. No patient died during follow‑up. The Fabry disease in Finland (the FinFabry study) assessed the clinical features of 97 Finnish FD patients. Classical FD was diagnosed in 59% of cases. The most common complication was FD‑related hypertrophic cardiomyopathy (FC), present in two‑thirds of men and half of women. FC was associated with worse outcomes, including atrial fibrillation, heart failure, and strokes. Nine patients died during follow‑up, almost all of whom had FC. ERT or migalastat was used by 69% of patients.