Skip to Main Content

We have a new app!

Take the Access library with you wherever you go—easy access to books, videos, images, podcasts, personalized features, and more.

Download the Access App here: iOS and Android. Learn more here!

Key Points

  • Disease summary:

    • Fabry disease is an X-linked lysosomal storage disease (LSD), which results from the deficient activity of the enzyme, α-galactosidase A (α-Gal A), and the lysosomal accumulation of glycosphingolipids with α-terminal galactosyl moieties, primarily globotriaosylceramide (GL-3).

    • Two major clinical subtypes have been described. The classic phenotype due to mutations that express little, if any, α-Gal A activity (<1% of mean normal) and present in childhood or adolescence, and a later-onset phenotype due to mutations that express residual enzyme activity (>1% of mean normal levels).

    • Newborn screening studies indicate the incidence in males of the classic phenotype to be about 1 in 25,000 to 40,000, while the later-onset phenotype is about 10 times more frequent in Europe and Taiwan.

    • Clinical manifestations of the classic phenotype include angiokeratoma, acroparesthesias, hypohidrosis, gastrointestinal symptoms, and a characteristic corneal keratopathy. With advancing age, the classic patients develop renal failure, cardiac disease, cerebrovascular disease, and premature demise.

    • Patients with the later-onset phenotype do not have endothelial glycosphingolipid deposition and lack the early manifestations of the classic phenotype. They develop renal failure, cardiac disease, or strokes later in life, typically between the third and fifth decades of life.

    • Enzyme replacement therapy (ERT) with recombinant α-Gal A has proven safe and effective in clinical trials.

  • Hereditary basis:

    • Fabry disease (both subtypes) is inherited as an X-linked trait. Manifestations in heterozygous females can range from as severely affected as males to asymptomatic, primarily due to random X-chromosomal inactivation. All daughters of an affected male are heterozygous, while all sons will not inherit the Fabry gene. On average, 50% of sons of a heterozygous mother will be affected and 50% of daughters will be heterozygotes.

  • Differential diagnosis:

    • Acroparesthesias:

      • Many of the symptoms in Fabry disease can be similar to those of other disorders, including rheumatoid or juvenile arthritis, rheumatic fever, erythromelalgia, lupus erythematosus, Raynaud syndrome, fibromyalgia, and multiple sclerosis. In children with acroparesthesias without any other major finding, “growing pains” may be attributed to their complaints.

    • Angiokeratoma:

      • Angiokeratomas, that are similar to or indistinguishable from the clinical appearance and distribution of the cutaneous lesions in Fabry disease, have been described in other lysosomal storage diseases, including fucosidosis (OMIM #230000), galactosialidosis (OMIM #256540), GM1-gangliosidosis (OMIM #230500), aspartylglucosaminuria (OMIM #208400), β-mannosidosis (OMIM #248510), and Kanzaki disease (OMIM #609242).

      • Angiokeratoma of Fordyce, angiokeratoma of Mibelli, and angiokeratoma circumscriptum are a few cutaneous disorders that have similar cutaneous lesions to those seen in Fabry disease. None have the typical histologic or ultrastructural lysosomal pathology of the Fabry lesion.

      • The angiokeratoma of Fordyce is similar in appearance to that of Fabry disease, but is limited to the scrotum, and usually appears after age 30.

      • The angiokeratomas of Mibelli includes warty lesions on the extensor surfaces of extremities in young adults and is associated with chilblains.

      • Angiokeratoma circumscriptum or naeviformus can occur anywhere on the body, is clinically and histologically similar to that of Fordyce, and is not associated with chilblains.

  • In adults, presence of ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.