Tetrahydrobiopterin Deficiency Medication

  • Author: Noah S Scheinfeld, MD, JD, FAAD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Aug 3, 2011
 

Medication Summary

Treatment of tetrahydrobiopterin (BH4) deficiencies consists of BH4 supplementation or diet to control blood Phe and supplements of folinic acid (10-20 mg/d) in dihydropteridine reductase (DHPR) deficiency.

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Pteridines

Class Summary

These replace the missing essential cofactor in the enzymatic hydroxylation of the 3 aromatic amino acids. Synthetic BH 4 (sapropterin) is now approved as an orphan drug by the US Food and Drug Administration (FDA).[17] Additional information can be viewed at the Tetrahydrobiopterin Web site.

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Sapropterin (Kuvan)

 

PO active synthetic form of (6R)-L-erythro-5,6,7,8-BH4 (a cofactor for PAH) that has received orphan drug status and fast track designation for the treatment of PKU. PAH hydroxylates phenylalanine through an oxidative reaction to form tyrosine. Treatment with BH 4 can activate residual PAH enzyme, improve normal oxidative metabolism of phenylalanine, and decrease phenylalanine levels in some patients.

Essential for hydroxylation of aromatic amino acids. Replaces missing cofactor. Dose based on specific phenotypic enzyme defect. Indicated to reduce blood phenylalanine levels in patients with HPA. Used in conjunction with a phenylalanine-restricted diet.

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Neurotransmitter precursors

Class Summary

These are used to supply necessary catecholamine replacement in the neurotransmitter pathway.

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Levodopa and carbidopa (Sinemet)

 

First-line treatment in conjunction with 5-HTP. Combination helps levodopa cross blood-brain barrier. Ratio prescribed for BH4 is 10:1 (levodopa 100 mg with carbidopa 10 mg).

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5-Hydroxytryptophan (5-HTP)

 

First-line therapy used in conjunction with levodopa. Aromatic amino acid and immediate precursor of serotonin. Orphan drug in United States (available from Circa Pharmaceuticals or Watson Laboratories).

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Vitamins

Class Summary

These increase levels of factors necessary in the amino acid pathways.

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Leucovorin (Wellcovorin)

 

Folinic acid (reduced form of folic acid that does not require enzymatic reduction for activation). First-line therapy in DHPR variant.

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Selective MAO B inhibitors

Class Summary

When high doses of neurotransmitters are necessary, the concurrent use of selective MAO B inhibitors is recommended because such use reduces the required dosage of administered precursors.

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Selegiline (Eldepryl)

 

Also known as L-deprenyl. Irreversible inhibitor of MAO. Possesses greater affinity for type B than for type A active sites. Can selectively inhibit MAO type B. Blocks breakdown of dopamine and extends duration of action of each dose of levodopa.

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Contributor Information and Disclosures
Author

Noah S Scheinfeld, MD, JD, FAAD  Assistant Clinical Professor, Department of Dermatology, Columbia University College of Physicians and Surgeons; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, and New York Eye and Ear Infirmary; Private Practice

Noah S Scheinfeld, MD, JD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Optigenex Consulting fee Independent contractor

Coauthor(s)

Elena L Jones, MD  Clinical Assistant Professor of Dermatology, Columbia University College of Physicians and Surgeons; Clinic Chief, Department of Dermatology, St Luke's-Roosevelt Hospital Center

Disclosure: Nothing to disclose.

Specialty Editor Board

Erawati V Bawle, MD, FAAP, FACMG  Retired Professor, Department of Pediatrics, Wayne State University School of Medicine

Erawati V Bawle, MD, FAAP, FACMG is a member of the following medical societies: American College of Medical Genetics and American Society of Human Genetics

Disclosure: Nothing to disclose.

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.

Robert Anthony Saul, MD  Clinical Professor, Department of Pediatrics, University of South Carolina; Senior Clinical Geneticist, Greenwood Genetic Center

Robert Anthony Saul, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, and American College of Physician Executives

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

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