Navigating Fabry Disease in a Military Aviator

BACKGROUND: Fabry disease (FD) is a rare, X-linked lysosomal storage disorder caused by deficient alpha-galactosidase A (alpha-Gal A) activity, leading to the accumulation of glycosphingolipids and resulting in a wide spectrum of systemic symptoms, including neurological, renal, cardiovascular, and cerebrovascular manifestations. While the disease affects approximately 1 in 100,000 individuals, its incidence may be underreported, and no cases in aviators have previously been documented.

CASE REPORT: A 30-yr-old U.S. Air Force C-5 pilot with a family history of FD was diagnosed with a pathogenic galactosidase alpha gene variant after genetic testing. Initial evaluations revealed proteinuric kidney disease and an otherwise normal neurological workup indicating early FD, prompting initiation of lisinopril, clopidogrel for stroke prevention, and the newly Food and Drug Administration-approved chaperone therapy migalastat. The patient tolerated treatment well with appropriate response to therapy as demonstrated by improved biochemical parameters (alpha-Gal A activity and plasma globotriaosylsphingosine levels) and clinical stability. After 8 mo of multidisciplinary monitoring and comprehensive evaluation, he was granted a time-limited aeromedical waiver and successfully returned to flying duties.

DISCUSSION: FD is a rare, progressive genetic disorder caused by galactosidase alpha gene variants, resulting in alpha-Gal A deficiency and glycosphingolipid accumulation, leading to neurological, renal, cardiac, and cerebrovascular complications. Despite higher aeromedical risks, especially due to stroke and cerebrovascular issues, FD patients may qualify for restricted flight duties under close monitoring and multidisciplinary care. Continued evaluation of novel therapies and individualized aeromedical waivers can support aviators with FD while balancing safety and operational requirements.

Carlock T, Kincaid-Sharp E, Orsello C, Ford AW, El-Khoury BB. Navigating Fabry disease in a military aviator. Aerosp Med Hum Perform. 2025; 96(6):525–529.