In Oslo, Norway, in 1934, an observant mother of two mentally retarded children noticed that their soiled diapers had an odd, musty odor. She mentioned this to Ivar Folling, a relative who was a physician and biochemist. Folling was intrigued. Analyzing the children's urine, he found large amounts of the amino acid phenylalanine, which is usually present only in trace amounts because an enzyme catalyzes a chemical reaction that breaks it down. The children lacked this enzyme because they had inherited an inborn error of metabolism called phenylketonuria, or PKU. The buildup of phe-nylalanine causes mental retardation.

Researchers wondered if a diet very low in phenylalanine might prevent the mental retardation. The diet would include the other nineteen types of amino acids so that normal growth, which requires protein, could occur.

The diet would theoretically alter the body's chemistry in a way that would counteract the overabundance of phenylalanine that the faulty genes caused.

In 1963, theory became reality when researchers devised a dietary treatment for this otherwise devastating illness (fig. 4A). The diet is very restrictive and difficult to follow, but it does prevent mental retardation. However, treated children may still have learning disabilities. We still do not know how long people with PKU should adhere to the diet, but it may be for their entire lives. ■

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