Details

Autor(en) / Beteiligte

• Nowak, Albina
• Krayenbuehl, Pierre-Alexandre
• Huynh-Do, Uyen
• Barbey, Frederic

Titel

Fabry disease genotype, phenotype and amenability: A full country overview

Ist Teil von

• Molecular genetics and metabolism, 2019-02, Vol.126 (2), p.S110-S111

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Fabry disease (FD) is a rare X-linked lysosomal storage disorder due to mutations in the α-galactosidase A gene (GLA) that result in deficiency of α-galactosidase A (α-GalA) enzymatic activity. As a result, the major glycosphingolipid substrates accumulate in plasma, urine and tissue lysosomes. There are two major phenotypes, classic and later-onset. Males with the more severe, classic phenotype have an α-Gal A activity of <1% and suffer early symptoms including acroparesthesias, angiokeratoma, corneal opacities and hypohidrosis, culminating in cardiomyopathy, kidney disease, and premature strokes in adults. The less severe, later-onset phenotype is characterized by an α-Gal A activity of >1%, asymptomatic childhood, but a progressive heart or kidney disease in adult males. The two phenotypic entities require different diagnostic and therapeutic strategies. Results: A total of 164 patients from 44 independent pedigrees, 61 affected males and 103 heterozygous individuals, have been diagnosed with FD in Switzerland since the year 1958. The ratio classic to later-onset phenotype was 3:1. Overall, 49% of the patients had amenable mutations, of those, 24% had classic and 25% later-onset phenotype. All patients with the later-onset phenotype had amenable missense mutations. While screening programs for FD have never been performed in Switzerland, mainly classic mutations were diagnosed in the past, later-onset mutations only being increasingly diagnosed recently. Conclusions Although the later-onset phenotype naturally occurs 10-20 times more frequently than the classic one, as shown in newborns screening studies, in our population, the prevalence of classic was considerably higher than later-onset phenotype, most likely because systematic screening for FD have never been performed in Switzerland. However, an increasing number of later-onset phenotype patients has been diagnosed in the recent time, due to increasing awareness of FD. Screening studies would help identify many so far undiagnosed later-onset patients.