Hyperphenylalaninaemia: therapy and follow-up

The term 'hyperphenylalaninaemia' includes different clinical phenotypes, characterized by plasma phenylalanine (phe) levels above 2 mg/dl. They are mostly due to various degrees of deficiency of phenylalanine hydroxylase, which lead to a progressive and severe mental retardation. Therapy is currently based on a phe restricted diet to be continued for life. This comprises foods very poor in whole animal proteins such as vegetables and fruits, special phenylanine lacking amino acid mixtures and proper lipidic and glucidic supplementations. The strict dietetary control, maintained by periodic clinical, nutritional and neurophysiological controls, makes the macronutrient intake closer to the recommended dietary allowances, but at the risk of inadequate intake of some specific components contained only in whole animal foods. Polyunsaturated very-long-chain fatty acids, carnitine, taurine and selenium are lower in treated hyperphenylalaninaemic children in comparison with healthy ones. A new challenge for the adequacy of the dietary intervention is represented by the management of maternal phenylketonuria, for the possible consequences on the developing tissues of the growing organism. The nutritional approach to the treatment of hyperphenylalaninaemic children may not only help to avoid consequences secondary to the dietary deficiencies (in particular those affecting the central nervous system), but may also represent a unique opportunity for better knowledge of the effects and consequences of specific nutrient deficiencies or supplementation, or both, on the metabolic status and body development.