Bilateral avascular necrosis: A rare complication of Fabry disease

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-orga...

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Main Authors: Candela Romano, Joel Wells, Nicholas Stanzione, Virginia Kimonis
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Molecular Genetics and Metabolism Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2214426925000345
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author Candela Romano
Joel Wells
Nicholas Stanzione
Virginia Kimonis
author_facet Candela Romano
Joel Wells
Nicholas Stanzione
Virginia Kimonis
author_sort Candela Romano
collection DOAJ
description 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.
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spelling doaj-art-0817d473ff194224a05a62a437fd3e462025-08-20T02:36:00ZengElsevierMolecular Genetics and Metabolism Reports2214-42692025-06-014310121910.1016/j.ymgmr.2025.101219Bilateral avascular necrosis: A rare complication of Fabry diseaseCandela Romano0Joel Wells1Nicholas Stanzione2Virginia Kimonis3Division of Genetics and Metabolism, Department of Pediatrics, University of California, Irvine, CA, USAMedical Director of the Comprehensive Hip Center Program & Hip Preservation Center, Baylor Scott & White McKinney Texas, Orthopedic Surgery Texas A&M School of Medicine, USADepartment of Pathology & Laboratory Medicine David Geffen School of Medicine, UCLA, USADivision of Genetics and Metabolism, Department of Pediatrics, University of California, Irvine, CA, USA; Department of Neurology, University of California, Irvine, CA, USA; Department of Pathology, University of California, Irvine, CA, USA; Children's Hospital of Orange County, Orange, CA, USA; Corresponding author at: Division of Genetics and Genomic Medicine, Department of Pediatrics, University of California Irvine, 101 The City Drive South, ZC4482, Orange, CA 92868, USA.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.http://www.sciencedirect.com/science/article/pii/S2214426925000345Fabry diseaseLysosomal storage diseaseAvascular necrosisOsteoporosisRare disease
spellingShingle Candela Romano
Joel Wells
Nicholas Stanzione
Virginia Kimonis
Bilateral avascular necrosis: A rare complication of Fabry disease
Molecular Genetics and Metabolism Reports
Fabry disease
Lysosomal storage disease
Avascular necrosis
Osteoporosis
Rare disease
title Bilateral avascular necrosis: A rare complication of Fabry disease
title_full Bilateral avascular necrosis: A rare complication of Fabry disease
title_fullStr Bilateral avascular necrosis: A rare complication of Fabry disease
title_full_unstemmed Bilateral avascular necrosis: A rare complication of Fabry disease
title_short Bilateral avascular necrosis: A rare complication of Fabry disease
title_sort bilateral avascular necrosis a rare complication of fabry disease
topic Fabry disease
Lysosomal storage disease
Avascular necrosis
Osteoporosis
Rare disease
url http://www.sciencedirect.com/science/article/pii/S2214426925000345
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AT nicholasstanzione bilateralavascularnecrosisararecomplicationoffabrydisease
AT virginiakimonis bilateralavascularnecrosisararecomplicationoffabrydisease