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Retired NBME 29 Answers

nbme29/Block 2/Question#8 (reveal difficulty score)
A male newborn is found to have increased ...
Metabolism of tetrahydrobiopterin ๐Ÿ” / ๐Ÿ“บ / ๐ŸŒณ / ๐Ÿ“–
tags: biochem

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submitted by โˆ—namesthegame22(13)
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  • Deficiencies in the enzymes required to synthesize or recycle BH4 result in a clinical syndrome that is largely indistinguishable from PKU, as BH4 is a necessary cofactor in the reactions catalyzed by PAH.

  • These disorders are inherited in an autosomal recessive fashion and treatment ES with oral replacement of BH4.

  • Metabolism of tetrahydrobiopterin (BH4) is deficient in a small subset of patients with phenylketonuria (PKU). The majority of patients with PKU have a deficiency in the enzyme phenylalanine hydroxylase (PAH) that converts phenylalanine to tyrosine. Deficiency results in accumulation of phenylalanine and its metabolites phenylacetate and phenyllactate.

  • However defects in enzymes that either produce or recycle BH4 can have similar clinical manifestations since BH 4 is a required cofactor for the function of PAH. It is also used as a cofactor for the enzymes tyrosine hydroxylase and tryptophan hydroxylase.

  • Autosomal recessive mutations in these enzymes result in impaired metabolism and recycling of BH4.

Clinical manifestations include neurotransmitter deficiency in addition to symptoms normally associated with PKU: microcephaly, skin disease, seizures, and intellectual disability.

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