⚗️ Metabolic Disorder

Fabry Disease

Also known as: Alpha-galactosidase A deficiency, GLA deficiency, Anderson-Fabry disease

Fabry disease is a rare, inherited lysosomal storage disorder caused by a deficiency of the enzyme alpha-galactosidase A (α-Gal A). This deficiency leads to the accumulation of globotriaosylceramide (Gb3) in various cells throughout the body, leading to a wide range of symptoms affecting multiple organ systems. The disease is X-linked, affecting both males and females, though females often have milder symptoms.

ICD-10: E75.21 Orphanet: 793 OMIM: 301500
👥 1 in 40,000 to 1 in 117,000 Prevalence
🔬 50 Active Trials

Imagine your body has tiny workers that clean up a certain type of sugar. In Fabry disease, these workers are broken, so the sugar builds up and causes problems in your heart, kidneys, and other parts of your body. Doctors can give you medicine to help clean up the sugar or fix the broken workers.

Signs & Symptoms

  • Angiokeratomas
  • Acroparesthesia (pain in hands and feet)
  • Corneal opacities
  • Renal dysfunction
  • Cardiomyopathy
  • Gastrointestinal problems
  • Heat and cold intolerance
  • Stroke
  • Tinnitus
  • Vertigo

Treatment Options

MEDICATION FDA Approved

Enzyme Replacement Therapy (ERT) - Agalsidase alfa

MODERATELY EFFECTIVE Approved 2003
MEDICATION FDA Approved

Enzyme Replacement Therapy (ERT) - Agalsidase beta

MODERATELY EFFECTIVE Approved 2003
MEDICATION FDA Approved

Chaperone Therapy - Migalastat

MODERATELY EFFECTIVE Approved 2018
MEDICATION FDA Approved

Pain management (NSAIDs, gabapentin, pregabalin)

SUPPORTIVE
SURGERY

Renal dialysis or kidney transplant (for end-stage renal disease)

SUPPORTIVE
MEDICATION FDA Approved

Cardiac management (medications for cardiomyopathy, arrhythmia)

SUPPORTIVE
GENE THERAPY

Gene Therapy

EXPERIMENTAL

Diagnosis

  • Enzyme assay (alpha-galactosidase A activity in leukocytes or plasma)
  • Genetic testing (GLA gene sequencing)
  • Kidney biopsy (to assess Gb3 accumulation)
  • Cardiac evaluation (ECG, echocardiogram, MRI)
  • Skin biopsy (to identify Gb3 deposits in endothelial cells)

History

Fabry disease was first described independently by Johannes Fabry and William Anderson in 1898. Fabry described a 13-year-old boy with angiokeratomas, while Anderson described a 39-year-old man with similar skin lesions and kidney disease. The underlying enzyme deficiency was not identified until the late 1960s, leading to the development of enzyme replacement therapy in the early 2000s.

Recent Breakthroughs

2018

FDA Approves Migalastat for Fabry Disease

The FDA approved migalastat, an oral pharmacological chaperone, for the treatment of Fabry disease in adults with amenable GLA variants. This provides an alternative to enzyme replacement therapy for a subset of patients.

2023

Gene Therapy Shows Promise in Early Clinical Trials

Early clinical trials of gene therapy for Fabry disease have shown promising results, with sustained increases in α-Gal A activity and reductions in Gb3 accumulation in some patients. Further studies are underway to evaluate the long-term safety and efficacy of this approach.