The Benefits of Family Screening in Rare Diseases: Genetic Testing Reveals 165 New Cases of Fabry Disease among At-Risk Family Members of 83 Index Patients

Genes (Basel). 2022 Sep 9;13(9):1619. doi: 10.3390/genes13091619.

PMID: 36140787

Sergey Moiseev, Ekaterina Tao, Alexey Moiseev

Highlights: This is the first study to have described family screening in a large Russian cohort of patients with FD and chronic kidney disease.

Abstract

Background: A functional lysosomal α-galactosidase deficiency causes the rare, progressive Fabry disease (FD, OMIM #301500), which causes an accumulation of glycosphingolipids in almost all of the body's cell types and fluids. Patients with rare genetic diseases and non-specific symptoms often experience substantial diagnostic delays, which can negatively impact the prompt initiation of treatment. End organ damage, such as chronic renal failure, hypertrophic cardiomyopathy with arrhythmia, and strokes, can worsen quality of life and shorten lifespan if FD is not specifically treated.

Patients and methods: Family trees were created and genetic testing (cascade genotyping) was made available to family members for 83 consecutive patients with FD who were sent to the Russian reference center for lysosomal storage diseases.

Results: For all 83 probands, the pathogenic GLA variation linked to FD was found. 165 new cases of FD were found among the 331 at-risk family members examined by family testing employing cascade genotyping.

Discussion: Family screening in a large Russian cohort of patients with FD and chronic renal disease was described in this study for the first time. For earlier diagnosis and targeted therapy, doctors' awareness of FD needs to be increased.

Keywords: Fabry disease, cascade genotyping, early diagnosis, family screening, rare diseases