Drug Delivery and Translational Research

, Volume 2, Issue 4, pp 223–237

Clinical therapeutics for phenylketonuria

  • Jaspreet Singh Kochhar
  • Sui Yung Chan
  • Pei Shi Ong
  • Lifeng Kang
Review Article

DOI: 10.1007/s13346-012-0067-1

Cite this article as:
Kochhar, J.S., Chan, S.Y., Ong, P.S. et al. Drug Deliv. and Transl. Res. (2012) 2: 223. doi:10.1007/s13346-012-0067-1

Abstract

Phenylketonuria was amongst the first of the metabolic disorders to be characterised, exhibiting an inborn error in phenylalanine metabolism due to a functional deficit of the enzyme phenylalanine hydroxylase. It affects around 700,000 people around the globe. Mutations in the gene coding for hepatic phenylalanine hydroxylase cause this deficiency resulting in elevated plasma phenylalanine concentrations, leading to cognitive impairment, neuromotor disorders and related behavioural symptoms. Inception of low phenylalanine diet in the 1950s marked a revolution in the management of phenylketonuria and has since been a vital element of all therapeutic regimens. However, compliance to dietary therapy has been found difficult and newer supplement approaches are being examined. The current development of gene therapy and enzyme replacement therapeutics may offer promising alternatives for the management of phenylketonuria. This review outlines the pathological basis of phenylketonuria, various treatment regimes, their associated challenges and the future prospects of each approach. Briefly, novel drug delivery systems which can potentially deliver therapeutic strategies in phenylketonuria have been discussed.

Keywords

PhenylketonuriaPhenylalanineHyperphenylalaninemiaPhenylalanine hydroxylasePhenylalanine ammonia lyase

Abbreviations

BH4

Tetrahydrobiopterin

DHPR

Dihydropteridine reductase

DNA

Deoxyribonucleic acid

EC

Enzyme Commission

EMEA

European Medicines Agency

ENU

Ethylnitrosourea

ERT

Enzyme Replacement Therapy

FDA

Food and Drug Administration

GMP

Glycomacropeptide

GTPCH

Guanosine triphosphate cyclohydrolase

HPA

Hyperphenylalaninemia

IQ

Intelligence quotient

LNAA

Large neutral amino acid

OMIM

Online Mendelian Inheritance in Man

PAH

Phenylalanine hydroxylase

PAL

Phenylalanine ammonia lyase

PCD

Pterin-4a-carbinolamine dehydratase

PEG

Polyethylene glycol

Phe

Phenylalanine

PKU

Phenylketonuria

qDHB

Quinonoid dihydrobiopterin

t-CA

Trans-cinnamic acid

Tyr

Tyrosine

Copyright information

© Controlled Release Society 2012

Authors and Affiliations

  • Jaspreet Singh Kochhar
    • 1
  • Sui Yung Chan
    • 1
  • Pei Shi Ong
    • 1
  • Lifeng Kang
    • 1
  1. 1.Department of PharmacyNational University of SingaporeSingaporeSingapore