Angiokeratoma Corporis Diffusum (Fabry Disease) Medication

Updated: Nov 21, 2019
  • Author: Fnu Nutan, MD, FACP; Chief Editor: William D James, MD  more...
  • Print

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Early intervention with enzyme replacement therapy (ERT) with intravenous infusions of recombinant human alpha-galactosidase A consistently and clearly decreases Gb3 levels in the blood plasma and clears vascular endothelial cellular lysosomal inclusions. While effects on other tissue are not so obvious, ERT, when initiated early, seems to prevent cellular damage and disease complications. [47] Certain genetic defects can make ERT less effective or totally ineffective and can lead to renal failure. [48]

Lidove et al [49] noted that two formulations of the enzyme alpha-galactosidase A are used in Europe: agalsidase alpha (produced in a human cell line) and agalsidase beta (produced in Chinese hamster ovary cells). Two different enzyme preparations are made by different companies: agalsidase alpha (Replagal, Shire) and agalsidase beta (Fabrazyme, Genzyme). Lin et al [50] found that patients can be switched form alpha-galactosidase to agalsidase beta with no ill effect after 1 year follow-up.

Lidove et al, [49] based on a review of 11 trials, reported that these preparations both appear to have clinical efficacy but that further assessments are needed. The trials have not been optimal in design. They would benefit from a prospective design and a specific investigation into the effects of ERT in women and on the use of ERT early in the course of Fabry disease to halt organ damage before it starts. Additionally, Kim et al [51] noted that the pulmonary manifestations of Fabry disease respond positively to ERT.

A report from France in 2012 [52] studied the use of miglustat hydrochloride, an investigational pharmacological chaperone, given orally at 150 mg every other day in two phase 2 studies. Researchers found miglustat hydrochloride increased α-Gal A activity by at the very least 50% in blood, skin, and kidney in 6 of 9 patients. In this study, α-Gal A activity also induced GL-3 reduction in skin, urine, and/or kidney. This is promising drug and is being studied in phase 3 studies.



Class Summary

Antiseizure medications are the most helpful in alleviating the debilitating pain of neurologic involvement.

Phenytoin (Dilantin)

Phenytoin may act in the motor cortex where it may inhibit the spread of seizure activity. Activity of the brainstem centers responsible for the tonic phase of grand mal seizures also may be inhibited.

Individualize dosing; if the dose cannot be divided equally, the larger dose should be taken before retiring for the evening.

Carbamazepine (Tegretol)

Carbamazepine may reduce polysynaptic responses and block posttetanic potentiation.


Enzymes, Metabolic

Class Summary

Enzyme replacement therapy stabilizes and may slow progression of Fabry disease, with more benefit when started at an early age.

Agalsidase alfa (alpha-Gal A)

Agalsidase alfa is a recombinant form of the human enzyme alpha-galactosidase A, levels of which are deficient in persons with Fabry disease. Data from clinical trials show a decrease in GL-3 levels following enzyme replacement, reversal in lipid tissue storage, stabilized or improved renal and cardiac function, and reduced or relief from neuropathic pain. Following enzyme replacement, long-term use of neuropathic pain medication has been reduced.

Agalsidase beta (Fabrazyme) is manufactured by Genzyme Corporation (Cambridge, Mass) and is based on the expression of the human GLA gene in CHO cells.

Agalsidase alfa (Replagal) is manufactured by Transkaryotic Therapies (Cambridge, Mass) and is based on activation of the human GLA gene expression in human (skin) fibroblasts.