BH4 Deficiency (Tetrahydrobiopterin Deficiency) Medication

Updated: Sep 28, 2018
  • Author: Anna V Blenda, PhD; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG  more...
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Medication

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.

See more details in Treatment and Medications.

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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). [53]  

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.

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).

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.

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.

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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