2 patients who are part of the history of medicine

I have two patients with phenylketonuria (PKU). Both are about my age. Laura, a non-verbal, slender woman with weathered features but the mind of a very young child, lives in the community. Her sister, Regina, has lived all her life in a nursing home. She doesn’t have a wrinkle in her face, and seems mostly unaware of her surroundings.

The two girls were born several years before Dr. Robert Guthrie developed the blood test for phenylketonuria, and a decade before routine PKU screening was introduced in this country. I often wonder what the parents of these two girls knew about their condition, where they went for a diagnosis, and if they even got one while Laura and Regina were still young. In many cases back then, PKU went undiagnosed as the specific cause of mental retardation.

Pulitzer and Nobel Prize winning author Pearl S. Buck gave birth to a daughter, Carol, in 1921. Carol did not develop normally, and on the advice of her Chinese doctors, Pearl Buck traveled to the Mayo Clinic to have her evaluated. She left the clinic and the United States without a diagnosis, except “I don’t know. Somewhere along the way, before birth or after, growth stopped.”

Pearl Buck cared for Carol at home until age nine. At that point she returned to America. She wrote “The Good Earth,” her book about her experiences in China, in 1931 with the hope of making enough money to support her daughter, who was institutionalized around that time. In 1950, she wrote “The Child Who Never Grew,” a memoir about her daughter. It wasn’t until ten years later that the cause of Carol’s mental retardation was finally diagnosed as phenylketonuria, the genetic disease that wasn’t even known until Carol was in her early teens.

The disease had first been described in Norway twenty years before Laura and Regina were born. Its discovery involved another set of siblings.

Dr. Asbjørn Følling, who had been a chemist before studying medicine, was asked to evaluate a brother and sister with severe mental retardation. His son, Ivar, told the story in a speech on the sixty year anniversary of this event in 1994:

The stage is set in 1934. A mother with two severely mentally retarded children came to see my father, and to ask for his advice…She had also noticed that a peculiar smell always clung to her children …

The girl, 6.5 years old, could say a few words, was fond of music, had a spastic gait and a whimsy way of moving about, apparently at random. At times she had an enormous appetite, at other times none. The boy, almost 4 years old, could not speak or walk, eat or drink on his own. He was unable to fix his eyes on anything, and stool and urine habits were those of a baby.

Dr. Følling’s son went on to describe his father’s painstaking chemical analyses of the children’s urine over the next several months that led to the realization that they both excreted phenylpyruvic acid, which healthy individuals don’t. The disease, phenylketonuria, is still called Følling’s disease in Norway.

The diet necessary for PKU patients was slowly established once Dr. Følling’s chemical analyses of urine hinted at their abnormal breakdown of the essential amino acid phenylalanine. An infant formula was developed in 1951. There are now protein supplements with low levels of phenylalanine, and also a pill that lowers phenylalanine levels, Kuvan (sapropterin), developed in the last decade.

Laura comes to see me every three to four months. I see her sister, Regina, every week during my nursing home rounds. When I see her, I always think about the life changing benefits of the newborn PKU test that came about in my own lifetime. Laura and Regina are part of the history of medicine, some of the last few with a cruel disease few doctors today have ever seen. I feel sad and humbled in the presence of these two contemporaries of mine, two children who never grew, but I also feel inspired by the steady progress of basic science.

“A Country Doctor” is a family physician who blogs at A Country Doctor Writes:.

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  • Ron Smith

    Hi, Country Doc.

    Thanks for sharing that. It really does send my thoughts flying.

    I seem constantly to get questions about delaying or passing altogether on vaccines. Polio was one of the illness I detailed in the ebook that I wrote for my parents. As I was researching it, I found many, many pictures of rooms filled with iron lungs.

    Even after three decades, I have never seen an iron lung in use in this country, just as I have never seen a case of untreated phenylketonuria. The solutions for both are equally and magnificently satisfying. We really do stand on the shoulders of many who dealt with so much worse in their time. I am grateful to Guthries and the Føllings before me.

    Warmest regards,

    Ron Smith, MD
    www (adot) ronsmithmd (adot) com