Phenylketonuria

Genetic Disorder

PKU is considered the most severe manifestation of hyperphenylalaninemia (too much phenylalanine in the body) and is inherited as an autosomal recessive trait due to phenylalanine 4-monooxygenase deficiency. Autosomal recessive traits refer to genetic conditions that occur only when mutations are present in both copies of a given gene. Commonly, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.

PKU allows the accumulation of excess phenylalanine and related components and disables the excretion of phenylalanine, phenylpyruvic acid, and other related compounds. In the developing world and regions where access to medical care, diagnosis, and adequate treatment are nonexistent, PKU can be deadly. However, if diagnosed early in the disease and early restriction of dietary phenylalanine is initiated, symptoms of the disease can be significantly reduced and prognosis is favorable.

Types of PKU

The signs and symptoms of PKU vary from mild to severe. The most common sign is a musty or mouse-like odor to the skin, hair, and urine from excess phenylalanine. Most common characteristics of severe form PKU are mental retardation, hypopigmentation of hair and skin, tumors, seizures, and eczema. Less severe forms of PKU (sometimes called moderate or mild PKU) have a smaller risk of brain damage. People with very mild cases may not require a therapeutic diet.

Also, women with PKU and uncontrolled phenylalanine levels have an increased risk of pregnancy loss altogether. This is significant in poorer countries where mothers may have mild forms of PKU or are currently under poor and intermittent treatment for PKU and do not have adequate access to prenatal care.

The most severe form of this disorder is known as classic PKU. Infants with classic PKU appear normal until they are a few months old and quickly develop symptoms. Without treatment of a special low-phe-nylalanine diet, these children develop permanent mental retardation and behavioral problems and can die. Other symptoms in more severe cases of PKU can involve seizures, extreme mental and physical development, vomiting and diarrhea with weight loss, photosensitivity, and abnormal movement disorders.

Epidemiology

Newborn screening and prompt treatment ensure the best outcome. As a result, the severe signs and symptoms of classic PKU are rarely seen where there is adequate resource and access to medical care, as in much of North America. In poorer parts of the world, most born with PKU may not make it past adolescence. The occurrence of PKU varies among ethnic groups and geographic regions worldwide. In the United States, PKU is detected in 1 in 10,000 to 15,000 newborns. Throughout the world, Turkey reportedly has the highest incidence with approximately 1 in 2,600 births. High incidence is also reported in the Yemenite Jewish population, as well as in regions of northern and eastern Europe, Italy, and China. There is no sex determination for PKU.

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