Clinical, genetic, and experimental research of hyperphenylalaninemia

Anqi Chen; Yukun Pan; Jinzhong Chen

doi:10.3389/fgene.2022.1051153

Clinical, genetic, and experimental research of hyperphenylalaninemia

Front Genet. 2023 Jan 4:13:1051153. doi: 10.3389/fgene.2022.1051153. eCollection 2022.

Authors

Anqi Chen¹, Yukun Pan², Jinzhong Chen³

Affiliations

¹ Department of Forensic Medicine, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
² Barbell Therapeutics Co. Ltd., Shanghai, China.
³ State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.

Abstract

Hyperphenylalaninemia (HPA) is the most common amino acid metabolism defect in humans. It is an autosomal-recessive disorder of the phenylalanine (Phe) metabolism, in which high Phe concentrations and low tyrosine (Tyr) concentrations in the blood cause phenylketonuria (PKU), brain dysfunction, light pigmentation and musty odor. Newborn screening data of HPA have revealed that the prevalence varies worldwide, with an average of 1:10,000. Most cases of HPA result from phenylalanine hydroxylase (PAH) deficiency, while a small number of HPA are caused by defects in the tetrahydrobiopterin (BH4) metabolism and DnaJ heat shock protein family (Hsp40) member C12 (DNAJC12) deficiency. Currently, the molecular pathophysiology of the neuropathology associated with HPA remains incompletely understood. Dietary restriction of Phe has been highly successful, although outcomes are still suboptimal and patients find it difficult to adhere to the treatment. Pharmacological treatments, such as BH4 and phenylalanine ammonia lyase, are available. Gene therapy for HPA is still in development.

Keywords: DnaJ heat shock protein family (Hsp40) member C12 (DNAJC12); dietary restriction; gene therapy; hyperphenylalaninemia (HPA); phenylalanine (Phe); phenylalanine hydroxylase (PAH); phenylketonuria (PKU); tetrahydrobiopterin (BH4).

Publication types

Review