Fabry disease is a rare X-linked recessive lysosomal storage disease. Multiple mutations of the GLA gene lead to a deficient or absent activity of the lysosomal enzyme α-galactosidase A, resulting in progressive glycotriaosylceramide accumulation in many organs. Low α-galactosidase A activity and mutations in the GLA gene confirm the diagnosis. Clinical signs are multisystemic, heterogeneous, and progressive. Renal, cardiac, and neurovascular involvements are the main life-threatening complications, highlighting the importance of an early initiation of enzyme replacement therapy improving long-term outcome. Fabry nephropathy lesions are characterized by a cell vacuolization of glomeruli, tubules, interstitium, and arteries and by ultrastructural myelin bodies. The main histologic differential diagnoses are toxicity of lysosomal inhibitors and other renal lipidoses. Renal biopsies are not necessary for diagnosis but have an important role in the evaluation of disease evolution and treatment efficiency, which is a major challenge for improving outcome and quality of life.
Hereditary breast and ovarian cancer syndrome is an autosomal dominant disease caused primarily by germline mutations in the BRCA1 or BRCA2 gene. Rare cases of double heterozygosity for BRCA1 and BRCA2 mutations have been reported quite exceptionally in non-Ashkenazi individuals. We describe the case of a woman who developed a bilateral breast cancer, discovered concomitantly, at 46 years old. Biopsies confirmed the presence of two breast cancers with distinct histology. BRCA analysis was tested due to a positive family history of breast cancer, and two pathogenic monoallelic mutations were detected, one in the BRCA1 gene and one in the BRCA2 gene. There is no known Ashkenazi Jewish ancestry. We report the first description of a never described double heterozygosity for BRCA1 and BRCA2 pathogenic variants in a French metastatic breast cancer patient, with two distinct histology, and two distinct mutations.
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