Bilateral avascular necrosis: A rare complication of Fabry disease

Abstract

Fabry disease is a rare X-linked lysosomal storage disorder caused by pathogenic variants in the GLA gene, which encodes for the α–galactosidase A enzyme responsible for degrading globotriaosylceramide. Its deficiency leads to the accumulation of GL3 in lysosomes, resulting in progressive multi-organ involvement, with predilection for the heart and kidneys.Clinical features associated with Fabry disease include acroparesthesia, angiokeratomas, hypohidrosis, corneal whorls, chronic kidney disease, cardiomyopathy, and strokes. Osteopenia and osteoporosis are less known complications, with rare reported cases of avascular necrosis of the hips.We report bilateral avascular necrosis in a 40-year-old-man diagnosed with Fabry at the age of 25 years. He carriers the familiar p.G328V GLA pathogenic variant. His Fabry features includes acroparesthesia, angiokeratomas, hypohidrosis, temperature and exercise intolerance, pain crises, abdominal pain and diarrhea, tinnitus, hearing loss, hypertrophic cardiomyopathy, palpitations, and chest pain. Family history reveals Fabry disease affecting multiple maternal relatives. The patient was recently diagnosed with avascular necrosis of the right hip requiring total arthroplasty due to failure of conservative treatment. Nine months later, he developed left hip pain attributed to avascular necrosis, also treated with total arthroplasty.This case highlights a rare skeletal complication of Fabry disease, underscoring the need for early diagnosis, optimizing treatment of Fabry disease, managing atypical comorbidities, and vigilant monitoring of bone health.

Keywords

• Fabry disease
• Lysosomal storage disease
• Avascular necrosis
• Osteoporosis
• Rare disease