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Genetics of Fabry Disease Medication

  • Author: Robert J Desnick, MD, PhD; Chief Editor: Maria Descartes, MD  more...
 
Updated: Feb 24, 2016
 

Medication Summary

Neuropathic pain agents and ERT may be indicated.

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Analgesics

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.

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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.

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Contributor Information and Disclosures
Author

Robert J Desnick, MD, PhD Dean for Genetics and Genomics, Professor and Chairman, Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine

Robert J Desnick, MD, PhD is a member of the following medical societies: American Society for Biochemistry and Molecular Biology, Eastern Society for Pediatric Research, American College of Medical Genetics and Genomics, American Pediatric Society, American Society for Clinical Investigation, American Society for Microbiology, American Society of Human Genetics, Central Society for Clinical and Translational Research, New York Academy of Sciences, Sigma Xi, Society for Experimental Biology and Medicine, Society for Pediatric Research

Disclosure: Received consulting fee from Amicus Therapeutics for consulting; Received consulting fee from Genzyme for consulting; Received grant/research funds from Genzyme for consulting; Received royalty from Genzyme for none; Received scientific advisory board from Genzyme for none; Received consulting fee from Synageva BioPharma for none; Received stock options from Synageva BioPharma for none; Received royalty from Shire HGT for none.

Coauthor(s)

Kenneth H Astrin, PhD Associate Professor of Human Genetics, Department of Human Genetics, Mount Sinai School of Medicine

Kenneth H Astrin, PhD is a member of the following medical societies: American Society of Human Genetics

Disclosure: Nothing to disclose.

Maryam Banikazemi, MD Assistant Professor of Clinical Pediatrics, New York Medical College

Maryam Banikazemi, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

Robert D Steiner, MD Chief Medical Officer, Acer Therapeutics; Clinical Professor, University of Wisconsin School of Medicine and Public Health

Robert D Steiner, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics and Genomics, American Society of Human Genetics, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Acer Therapeutics; Retrophin; Raptor Pharma; Veritas Genetics; Censa Pharma<br/>Received income in an amount equal to or greater than $250 from: Acer Therapeutics; Retrophin; Raptor Pharma; Censa Pharma.

David Flannery, MD, FAAP, FACMG Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia

David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics

Disclosure: Nothing to disclose.

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Angiokeratoma is the small punctate reddish-to-bluish angiectases on the umbilicus.
Angiokeratomas are commonly observed as dense cluster of lesions on the flank and private areas.
Corneal verticillata, commonly seen in patients with Fabry disease, detectable by slit lamp examination.
 
 
 
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