Mysterious untreatable fevers once devastated whole families. This doctor discovered what caused them

Dr. Daniel Kastner, right, in his lab in 2018 with Dr. Kalpana Manthiram, a clinical fellow at the National Human Genome Research Institute and a colleague of Kastner.

(CNN)It's an ancient disease that may have evolved to confer protection against the plague -- but until 20 years ago, it had scientists and doctors flummoxed.

They couldn't explain why those afflicted, often in the same family, had recurring fevers, abdominal pain, troublesome rashes and muscle aches. Known as familial Mediterranean fever, the disease often went undiagnosed for years, and it was sometimes fatal.
Unusual in most parts of the world, it was more common in the countries that border the Eastern Mediterranean -- including Turkey and Israel -- where one or two of every 1,000 people have it.
    A similar, but unrelated, mystery fever was initially thought to affect families with Scottish and Irish heritage.
      While these types of periodic fevers, now classed as autoinflammatory disorders, are regarded as rare, they cause misery for those who suffer from them.
        "The pain I felt back then, it moved around. One week the pain was in my leg, and the next week my arm would hurt instead," said Victoria Marklund, 47, a Swedish woman who suffered from TRAPS, or tumor necrosis factor receptor-associated periodic syndrome, a disease first identified in a family of Irish and Scottish descent living in the UK city of Nottingham in 1982.
        Her father and grandfather died prematurely from kidney complications, which were likely a consequence of the undiagnosed disorder.
          Marklund has now received an effective treatment and lives symptom-free -- largely thanks to the work of one US physician and health researcher, Dr. Dan Kastner, a distinguished investigator at the National Institutes of Health who serves as scientific director of the National Human Genome Research Institute.
          The Royal Swedish Academy of Sciences on Monday awarded Kastner the prestigious Crafoord Prize, considered a complement -- and for some winners, a precursor to -- a Nobel prize.
          "What Dr. Kastner has accomplished is absolutely groundbreaking. The concept of autoinflammatory disorders didn't exist before he identified the cause behind a number of them," said Olle Kämpe, a professor of clinical endocrinology at Karolinska Institutet in Stockholm who is a member of The Royal Swedish Academy of Sciences and chair of the Prize Committee. The academy also selects Nobel laureates.
          Dr. Dan Kastner (center) is shown in his NIH lab in 1990 with his colleagues Dr. Ivona Aksentijevich and Dr. Luis Gruberg.
          "His discoveries have taught us a great deal about the immune system and its functions, contributing to effective treatments that reduce the symptoms of disease from which patients previously suffered enormously," Kämpe added.


          Kastner first came across familial Mediterranean fever in a patient with recurring arthritis and high fevers he treated as a rheumatology fellow just months into his first job at the NIH in Bethesda, Maryland, in 1985. That chance diagnosis set him on a 12-year journey to find the gene -- or genes -- responsible for the disease.
          "It was known that familial Mediterranean fever was a genetic disease. It was known that it was recessively inherited, but no one knew what the gene was, or even the chromosome," he said.
          He traveled to Israel, where he took blood samples from 50 families with familial Mediterranean fever.
          It took Kastner seven years to locate the mutation to chromosome 16. It took another five years -- in 1997 -- for Kastner and his team to find the mutated gene itself -- one misprint in a genetic code comprised of 3 billion letters.
          After this breakthrough, he stayed at NIH, where he studied undiagnosed patients with similar symptoms. He identified 16 autoinflammatory genetic disorders and found effective treatments for at least 12 of them, establishing a whole new field of medicine.