Phenylketonuria is a disease well-known even among the general public. It is an inherited metabolic disorder that occurs in about one out of 10,000 births. Phenylketonuria has some significant features – the early detection is possible and recognizing the disease allows us to start with an efficient treatment that can prevent the otherwise inevitable disability of the patient.


Phenylketonuria is an inherited disorder of the metabolism of amino acids phenylalanine and tyrosine. The disease has several forms, but all of them, there is disrupted chemical conversion of phenylalanine to tyrosine. This problem has more consequences. First, the body misses the amino acid tyrosine that is not created by the chemical reaction. In addition, the phenylalanine accumulates in the body as it is not converted to tyrosine.


Genetic note: Phenylketonuria is an autosomal recessive transmitted disease. Simply said, there are two genes and every person gives one of theses genes to his or her child. When the child gets two healthy genes, he or she is completely healthy. The bearer of one healthy and one defective gene is healthy but we call him or her a carrier (as the faulty gene can be further transmitted to his or her children). A person with two faulty genes has the symptoms of the disease. When a carrier-male meets a carrier-woman, there is a chance that their child will be transmitted both faulty genes and gets ill.


Missing amino acid tyrosine is required for the formation of melanin. Melanin is a pigment of hair, skin and eye. Its deficiency therefore results in blue eyes, blond hair and pale skin in children suffering from phenylketonuria. Accumulated phenylalanine is converted to other compounds that are toxic and have a negative effect on the child, particularly on the brain development. The disease manifests in the newborn by vomiting, convulsions and abnormal movements. The most important symptom is the gradually developing mental retardation. Once this occurs, nothing can be done as the decrease of intelligence is irreversible.


The doctors can diagnose the disease before the onset of symptoms. In many civilized countries there is a special examination of the newborns. The pediatricians get a drop of blood from the child’s heel and use genetically engineered bacterial culture of Bacillus subtilis. These bacteria are unable to produce their own phenylalanine and survive only in contact with blood with accumulated phenylalanine. This method is known as the Guthrie test. The time of the blood sampling should be about four days after the start of the milk feeding. Milk contains proteins and these contain the phenylalanine. After four days of milk digestion, the levels of blood phenylalanine are high enough to make the test positive in affected children.


When the test is positive, there is a high risk of phenylketonuria and other test including genetic testing must be done to confirm the diagnosis.


The disease in incurable as it is inherited and genetically caused. Despite that, we have therapeutic methods to prevent the symptoms occurrence. The only option is to administer a special diet that is low on phenylalanine and regularly measure the concentration of phenylalanine in the blood of the patient. This precaution must be strictly held until the 20 years of age, when the brain is no longer sensitive to high levels of phenylalanine. However, the low phenylalanine diet is advisable even for adults because there is supposed a relationship between inadequately treated phenylketonuria and earlier onset of the Alzheimer's disease.


Another danger is pregnancy of women suffering from phenylketonuria. The above mentioned strict diet must be kept for the whole pregnancy period as the high concentration of phenylalanine gets through placenta into the embryo and can damage its brain.


Jiri Stefanek, MD  Author of texts: Jiri Stefanek, MD
 Sources: basic text sources