Genetics of Fabry Disease Medication

Updated: Aug 23, 2018
  • Author: Robert J Desnick, MD, PhD; Chief Editor: Maria Descartes, MD  more...
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Medication Summary

Neuropathic pain agents, enzyme replacement therapy (ERT), or α-galactosidase A (α-Gal A) stabilizers may be indicated.



Class Summary

These agents are used to relieve neuropathic pain. Phenytoin and carbamazepine are 2 medications used to treat acroparesthesias in patients with Fabry disease. Either drug may be used, although some patients benefit from a combination.

Phenytoin (Dilantin)

Used for analgesia for acroparesthesia. May act in the motor cortex, where it may inhibit spread of seizure activity. Activity of the brainstem centers responsible for the tonic phase of grand mal seizures may also be inhibited. Individualize dose. Administer larger dose before bedtime if dose cannot be equally divided.

Carbamazepine (Tegretol)

Indicated for complex partial seizures and trigeminal neuralgia. May block posttetanic potentiation by reducing summation of temporal stimulation. May reduce polysynaptic responses and block posttetanic potentiation. Following therapeutic response, may reduce dose to minimum effective level or discontinue treatment at least once every 3 mo. Doses are typically lower than those used to treat seizures and are administered once daily.

Gabapentin (Neurontin)

FDA-approved PO medication for management of postherpetic neuralgia. Also FDA approved for the treatment of partial seizures in adults and children. Chemical structure similar to the inhibitory neurotransmitter GABA. Appears to work by raising GABA levels by some effect on a GABA transporter protein. Also decreases activity of voltage-gated calcium channels via binding to a secondary protein. Approved for epilepsy in children. Available as tab, cap, and liquid dosage forms.


Enzyme Replacement Therapy

Class Summary

α-Gal A deficiency leads to the accumulation of GSLs with terminal α-galactosyl residues. Clinical manifestations of Fabry disease are reflected in the tissue target sites of lipid storage. The recombinantly produced enzyme α-Gal A is available in Europe and United States.

Agalsidase alfa (Fabrazyme, Replagal)

Recombinant form of the human enzyme α-Gal A, which is deficient in patients 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 reduction or relief of neuropathic pain. Following enzyme replacement, the long-term use of neuropathic pain medication has been reduced. Agalsidase beta (Fabrazyme) is manufactured by Genzyme Corporation (Cambridge, Mass) and is based on expression of the human GLA gene in CHO cells. Agalsidase alfa (Replagal) is manufactured by Transkaryotic Therapies, Inc (Cambridge, Mass) and is based on activation of the human GLA gene expression in human (skin) fibroblasts.


Alpha-Galactosidase A Stabilizers

Class Summary

Binding to and stabilizing endogenous α-galactosidase A (α-Gal A), migalastat chaperones the enzyme from the endoplasmic reticulum to lysosomes, where α-Gal A can degrade the accumulated glycolipid (globotriaosylceramide [GL-3]) and globotriaosylsphingosine (lyso-Gb3).

Migalastat (Galafold)

Indicated for adults in whom a diagnosis of Fabry disease has been confirmed and who possess an amenable galactosidase-α gene (GLA) variant (as determined through in vitro assay data).