Tetrahydrobiopterin (Bh4) deficiencies: diagnosis and treatment

Abstract

Tetrahydrobiopterin (BH4) is an enzyme cofactor of phenylalanine hydroxylase, tyrosine hydroxylase and tryptophan hydroxylase. Three different enzymes affect BH4 synthesis: guanosine triphosphate cyclohydrolase I (GTP CH 1), 6-piruvoil tetrahydropterin synthase (PTPS), sepiapterin reductase (SR) and dihydropteridine reductase (DHPR) affects regeneration. BH4 deficiency causes defects in monoaminergic neurotransmitters synthesis and can be or not associated with hyperphenylalaninemia (HPA). Symptoms often begin in the first months of life with mental retardation, dystonic movements and posture, temperature control disorders, seizures, abnormal posture and tone, salivation and swallowing difficulties. Diagnosis is based on the following tests: pterins in urine, neurotransmitters and pterins in cerebrospinal fluid, reduced enzyme activity (in blood or fibroblasts) and mutational analysis. Treatment should be directed to normalize blood Phe levels and brain neurotransmitters with the administration of BH4 10 mg / kg / d, L-DOPA 10 mg/kg/day and 5-OH-tryptophan, 5 to 6 mg/kg/day. LDOPA should be given with carbidopa in order to inhibit the destruction of the L-dopa by the carboxylase. We describe 3 patients with BH4 deficiency treated at the Ramon y Cajal Hospital. All of them had a good neurological outcome with almost normal mental development.

Keywords

• Tetrahidrobiopterina
• hiperfenilalaninemia
• sapropterina
• tratamiento
• diagnóstico