Management of phenylketonuria: Current and future perspectives

Abstract

Phenylketonuria (PKU) is an inborn error of phenylalanine (phe) and tyrosine (tyr) metabolism. It is an autosomal recessive disease occurred due to deficiency of liver enzyme phenylalanine hydroxylase (PAH). Hence, phe is not converted to tyr and phe is accumulated in the body. Phe thus channeled to alternative routes of metabolism and forms Phenylketones excreted in urine. Early treatment is essential to prevent mental retardation and other intellectual disabilities. Dietary treatment remains the main cornerstone to manage PKU since last 3-4 decades. A diet low in Phe supplemented with special amino acids formulas must be started soon after diagnosis within seven days of life. Inspite of good results obtained from dietary treatment in PKU, still there are some issues with palatability of the dietary formulations. There are also issues of nutritional deficiencies of vitamins like calcitriol and cobalamin (B12). Poor cognitive and executive functions have been observed in patients who do not follow proper dietary treatment. Attempts have also been made to increase the palatability of food under dietary management. Role of large neutral amino acids (LNAAs) and glycomacropeptides (GMP; found in bovine milk) as a newer dietary management have also been explored. In recent era, advances occurred in terms of genetic therapy and enzyme replacement therapy which opened a new door towards management of PKU. In this review, various treatment aspects of PKU are discussed and explored.