Hyperphenylalaninemia (HPA)

Phenylalanine (Phe) is an essential amino acid derived from protein consumed as part of a normal diet. Hyperphenylalaninemia (HPA) is defined as an abnormal elevation of Phe in the blood.

HPA generally occurs as a result of two inborn errors of metabolism: phenylketonuria (PKU) or tetrahydrobiopterin (BH4) deficiency.

PKU is a hereditary metabolic disorder caused by a genetic mutation leading to a deficiency or reduced activity of the enzyme phenylalanine hydroxylase (PAH).  PAH is required for the metabolism of Phe. If the enzyme activity is insufficient, Phe accumulates to abnormally high levels in the blood and brain. If untreated, this can lead to a variety of complications including severe mental retardation and brain damage, mental illness, seizures and tremors, and cognitive problems.

Although it is a rare disease, PKU is one of the most common genetic metabolic disorders. Approximately one in 8,000 children in Europe is born with PKU1, although the incidence varies among countries. The incidence in the UK is approximately 1 in 10,000 live births (1 in 4,500 in Northern Ireland).2

BH4  deficiency is a very rare inborn error of metabolism, estimated to account for less than 2% of HPA3.  BH4 is the natural cofactor for the PAH enzyme (a cofactor is a non-protein substance that is essential for the enzyme to work).

If newborns are left untreated from birth, the neurological damage caused by HPA can result in serious brain damage and, if insufficiently controlled, HPA can cause transient to lasting impairments in children and transient impairments in adults.

HPA/PKU is currently managed with a strict, ideally life-long diet aimed at maintaining blood Phe levels as low as possible within clinically accepted range.2,4  A typical low-Phe diet does not allow foods rich in protein e.g. meat, fish, cheese, nuts, seeds or eggs. Supplements are added to the diet to provide essential amino acids, vitamins, trace elements and minerals that are in low supply due to dietary restrictions5.

Foods such as bread, pasta and rice also contain protein, so only small, measured quantities are allowed in the diet of patients with PKU. Manufactured low-Phe foods such as low-protein breads, rice, biscuits and pasta are available to supplement the diet.5
 
1. Loeber JG. Neonatal screening in Europe: the situation in 2004.  J Inherit Metab Dis 2007; 30: 430–438.

2. National Society for Phenylketonuria (NSPKU). Management of PKU. Feb 2004 http://www.ukonline.co.uk/nspku (date accessed 11/09/2008).

3. de Baulny HO, Abadie V, Feillet F, de Parscau L. Management of phenylketonuria and hyperphenylalaninemia. J Nutr 2007; 137: 1561S-1563S; discussion 1573S–1575S.

4. Medical Research Council Working Party on Phenylketonuria 1993b. Recommendations on the dietary management of phenylketonuria. Arch Dis Child 1993; 68: 426-427.

5. National Society for Phenylketonuria (NSPKU). Dietary information for the treatment of phenylketonuria 2007/2008 Revision. Accessed at www.nspku.org