[Tetrahydrobiopterin (BH₄) deficiency - diagnosis and treatment]

Since the initial breaking discovery of Følling that the severe neurological consequences of phenylketonuria could be prevented by use of low phenylalanine (Phe) diet, it has been shortly recognised that defective phenylalanine metabolism may also arise from the deficiency of tetrahydrobiopterin (BH₄) cofactor, required for phenylalanine-hydroxylase activity. Furthermore, as BH₄ is in Phe metabolism, it is also a cofactor for the activities of tyrosine hydroxylase and tryptophane hydroxylase, enzymes required for the synthesis of catecholamines and serotonin neurotransmitters. Besides hyperphenylalaninemia in patients with tetrahydrobiopterin deficiencies, dopamine and serotonin deficiencies, with different disorders of the central nervous system also develop. Mild form of tetrahydrobiopterin deficiency is rare, most of the patients have severe neurological abnormalities including progressive mental retardation if not treated properly. Early diagnosis and treatment are essential and can improve the clinical course and prognosis. Orv Hetil. 2017; 158(48): 1897-1902.