๐Ÿงฌ 653.6 ยท Fabry Disease (Anderson-Fabry Disease)

Nelson Textbook of Pediatrics 22nd Edition โ€” X-linked lysosomal storage disorder due to GLA mutations (ฮฑ-galactosidase A deficiency). Accumulation of globotriaosylceramide (Gb3). Acroparesthesias (burning pain), angiokeratomas, hypohidrosis, corneal opacities (cornea verticillata), progressive renal failure, hypertrophic cardiomyopathy, stroke. Enzyme replacement therapy (agalsidase alfa/beta).

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๐Ÿฉบ Clinical Recognition: Fabry Disease

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๐Ÿ“‹ Stepwise Management of Fabry Disease

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    Clinical Features of Fabry Disease

    SystemManifestations
    Neurologic (small fiber neuropathy)Acroparesthesias (burning pain in hands/feet), episodic pain crises (fever, exercise, stress), hypohidrosis (decreased sweating), autonomic dysfunction
    DermatologicAngiokeratomas (red-black telangiectasias) โ€” perineum, scrotum, buttocks, periumbilical; hypohidrosis
    OcularCornea verticillata (whorl-like corneal opacities) โ€” pathognomonic; cataracts, tortuous retinal vessels
    RenalProteinuria, progressive renal insufficiency, end-stage renal disease (3rd-4th decade)
    CardiacHypertrophic cardiomyopathy (LVH), conduction defects, arrhythmias, valvular disease, coronary artery disease
    CerebrovascularStroke (ischemic/hemorrhagic) at young age, white matter lesions
    GastrointestinalAbdominal pain, diarrhea, postprandial bloating
    ๐Ÿ’Š Enzyme Replacement Therapy (ERT)

    Agalsidase alfa (Replagal) and agalsidase beta (Fabrazyme): Recombinant human ฮฑ-galactosidase A. IV infusion every 2 weeks. Reduces pain, stabilizes renal function, reduces LVH. Best results with early initiation before organ damage.

    Chaperone therapy (migalastat, Galafold): Oral small molecule for patients with amenable GLA mutations (certain missense mutations). Improves enzyme activity. Not for null mutations.

    Pain management: Gabapentin, pregabalin, carbamazepine for neuropathic pain. Avoid triggers (heat, exercise).

    Data from Nelson 653.6; Manzur AY. Fabry disease.

    ๐Ÿ“– Summary: Fabry Disease โ€” Nelson 653.6