Alpha-galactosidase deficiency

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X-linked lysosomal storage disorder

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  • Presumptive if[1]:
    • Birefringent inclusions in urinary sediment
    • Corneal dystrophy on slit-lamp examination
    • Skin biopsy with refractile lipid inclusions (Maltese crosses) in endothelial cells
  • Definite if:
    • Measurement of α-galactosidase-A activity in leukocytes or fibroblasts of affected men
    • Detection of a mutation in the α-galactosidase-A gene in female heterozygotes

Alpha-galactosidase deficiency (Fabry disease, Fabry syndrome, Anderson-Fabry syndrome) is caused by gene variations that result in deficiency in lysosomal alpha-galactosidase.

Leads to an excess of glycosphyngolipids (globotriaosylceramide, Gal-Gal-Glc-Cer) in the lysosomes of various tissues and organs. Clinical symptoms are related to heart, skin, kidneys and nervous system.

Contents

Clinical Features

Males

The full syndrome has:

  • Characteristic skin lesions (angiokeratomas, purpura papulosa haemorrhagica Hebrae) over the lower trunk but can be absent
  • Corneal deposits (corneal verticillata, Fleischer vortex dystrophy, whorl-like corneal dystrophy)
  • Febrile episodes
  • Burning pain in the extremities due to small-fiber peripheral neuropathy.
  • Early death from renal failure and cardiac or cerebral complications of hypertension
  • Possibly short PR interval (prediposes to potentially malignant arrhthmias)
  • Possibly mitral valve prolapse
  • Possibly high frequency sensorineural deafness or tinnitus
  • Possibly hypohidrosis or anhidrosis with associated heat intolerance

Residual enzyme function results in a cardiac form manifesting about 60 years of age with:

  • Left ventricular hypertrophy
  • Sometimes renal failure

Females

If heterozygous may have an attenuated form

  • Corneal opacities commoner than in males

Both

Attenuated forms which are likely to be underdiagnosed can present with:

  • Strokes in the third or fourth decade[2].
  • Chronic exercise-induced pain, cramps, and fasciculations

Investigations

Treatment

References