Which deficiency is linked to BH2 reductase?

BH2 reductase, also known as dihydrobiopterin reductase, is an enzyme involved in the regeneration of tetrahydrobiopterin (BH4), an essential cofactor for several aromatic amino acid hydroxylases, including phenylalanine hydroxylase. A deficiency in this enzyme leads to an inability to properly metabolize phenylalanine, resulting in elevated levels of phenylalanine in the blood and a condition referred to as malignant phenylketonuria (PKU).

Malignant PKU is characterized not only by the accumulation of phenylalanine but also by more severe symptoms than classic PKU, including neurological deficits and changes in cognitive function. This is because BH4 also plays a critical role in the synthesis of neurotransmitters, including serotonin and dopamine. Therefore, BH2 reductase deficiency impacts both metabolic pathways involving phenylalanine and neurotransmitter production, leading to the severe manifestations associated with malignant PKU.

Other conditions mentioned, such as albinism, cystathionine beta-synthase deficiency, and classic PKU, are linked to different metabolic pathways or enzymatic deficiencies. Albinism is caused by defects in melanin production, cystathionine beta-synthase deficiency is