The history of Phenylketonuria (PKU)?

Question

Please cite sources :-)

Answer 1

Weeeeeell, the discovery of it (or the cause behind it anyway) took place in Norway in 1934. A doctor named Asbjorn Folling was asked by a mother, Mrs. Egeland, to see what it was that was making her kids act so odd. They couldn't talk, one couldn't walk, they were light skinned and smelled sort of like a sweaty locker room. He did a urine test and found there was some very uncommon substance, a ketone, in there. When he did some old-school organic chemistry to find it, it ended up being phenylpyruvic acid (which is used today in acrylics as an industrial solvent.) It's a phenylketone in the urine---hence the name of the disorder. He figured it had to do with the metabolism of phenylalanine, an amino acid you'll find in all complete protein.

Dr. Horst Bickel was the guy who figured out that a low-phenylalanine diet worked to improve the symptoms of PKU. You can actually find a video online of the adorable little girl who was his first patient in this case, in the 1950s. The change was amazing--although the brain damage had already been done, she did improve and seemed so much happier, which was great! Dr. Bickel replaced natural protein with a sort of nutritional supplement drink (a "formula") that contained every nutrient & amino acid except PHE.

Then came Dr. Robert Guthrie in the late 50s and early 60s, who came up with the Guthrie bacterial inhibition assay or "Guthrie spot." The original required that a baby's heel be pricked and blood be applied in tiny amounts to a card with parts that are punched out at the lab. Then these would be put into a sort of bacterial "soup" using Proteus vulgaris, a bacteria that grows and thrives when PHE levels are high. Now, tandem mass spectrometers are used to do that, not bacteria.

The most interesting thing about it is that Dr. Guthrie traveled in a van across the nation to campaign for newborn screening. Now every state in the US does it, as do many nations. Folks who do have PKU are treated right away, and the horrible damage that came from it in the past has really started to become the stuff of legend--you only hear about it, but rarely if ever see it. As for your average guy or gal with PKU now, you would never know it by looking at them or watching them.

And as for Mrs. Egeland, she was honored by the Norwegian government for her persistence and ultimately helping tens of thousands of people worldwide. She was awarded a traditional ferret statue, a symbol of perseverence, before her passing. The moral of the story here---ALWAYS listen to a concerned mother.

Answer 2

Phenylketonuria is a clinical syndrome of mental retardation with cognitive and behavioral abnormalities caused by elevated serum phenylalanine. The primary cause is deficient phenylalanine hydroxylase activity. Diagnosis is by detecting high phenylalanine levels and normal or low tyrosine levels. Treatment is lifelong dietary phenylalanine restriction. Prognosis is excellent with treatment.
Phenylketonuria was discovered by the Norwegian physician Ivar Asbjørn Følling in 1934 when he noticed that hyperphenylalaninemia (HPA) was associated with mental retardation. In Norway, this disorder is known as Følling's disease, named after its discoverer. Dr. Følling was one of the first physicians to apply detailed chemical analysis to the study of disease. His careful analysis of the urine of two retarded siblings led him to request many physicians near Oslo to test the urine of other retarded patients. This led to the discovery of the same substance that he had found in eight other patients. The substance found was subjected to much more basic and rudimentary chemical analysis than is available today. He conducted tests and found reactions that gave rise to benzaldehyde and benzoic acid, which led him to conclude the compound contained a benzene ring. Further testing showed the melting point to be the same as phenylpyruvic acid, which indicated that the substance was in the urine. His careful science inspired many to pursue similar meticulous and painstaking research with other disorders.
Please see the web pages for more details on Phenylketonuria.