Detective doctors solve more than 100 baffling medical mysteries

Their Sherlock Holmes-like sleuthing has unearthed 31 new syndromes

For years, one man’s mysterious and life-threatening episodes of lactic acidosis, seemingly prompted by a cold or a bout of the flu, remained unsolved.

Then a US network of doctors with Sherlock Holmes-like dedication stepped in and sleuthed out a new syndrome.

Following a gamut of tests, including genome sequencing, the culprit was identified: a single mutation in the gene ATP5F1D, which is involved in the function of mitochondria.

The genetic oddity and symptoms had never been classified together officially.

But through the network and word of mouth it was revealed that other doctors around the world had patients plagued by the syndrome too.

This is just one of 132 baffling cases, some which have lasted decades, which have been solved by the Undiagnosed Disease Network (UDN), according to a new study in the New England Journal of Medicine.

Among the cases the network has diagnosed are 31 new syndromes and 24 unusual presentations of a known syndrome.

In 80% of cases a diagnosis has led to actionable information, such as a change in therapy, adjustments to future diagnostic testing or a recommendation for family screening.

The network was established in 2014 when the US National Institutes of Health established a consortium of multidisciplinary doctors and unravel the most bamboozling of medical cases at no charge to the patient.

Dr Euan Ashley, a professor of medicine at Stanford University, was asked to chair the group.

The current study explored what happened to 601 children and adults, 40% with neurological symptoms, who were accepted for evaluation over a 20-month period.

By the end of the study period, 382 had been fully evaluated through standardised phenotyping and most also underwent exome or genome testing.

Some 74% received a diagnosis after exome or genome sequencing and 11% by clinical review.

Just over half (53%) of the 132 diagnoses were recognised presentations of a known syndrome.

Among the new syndromes identified, 15 were associated with a new gene or gene region.

Around one-third of patients who had undergone previous sequencing received a diagnosis this time around.

"We do this Sherlock Holmes-like detective work-up by carefully observing, gathering information and asking pointed questions, but we're also pairing that with the most advanced genomic technologies to try to solve their case," Professor Ashley said.

"Some cases are solved simply because we know more today than we did a year ago.”

Among the patients who received a diagnosis, the average cost of care prior to UDN evaluation was nearly $432,000 and the average cost of the evaluation was $26,734.

“These cost estimates suggest that the UDN approach has the potential to cut short an expensive medical diagnostic odyssey, and they are consistent with recent cost-effectiveness analyses for genome sequencing,” the study authors wrote.

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