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New primer highlights latest understanding of rare inherited disease alkaptonuria

12 March 2024: Researchers have published a comprehensive new primer on alkaptonuria (AKU), a rare inherited metabolic disorder, in the journal Nature Reviews Disease Primers. The primer provides an up-to date overview of this poorly understood condition.

AKU is caused by a deficiency in the enzyme homogentisate 1,2-dioxygenase due to mutations in the HGD gene. This leads to a buildup of homogentisic acid (HGA) in the body, which over time becomes deposited in connective tissues in a process called ochronosis.

Key points highlighted in the primer include:

  • Alkaptonuria is extremely rare, affecting only 1 in 250,000 to 1 million people globally, though rates are higher in certain populations.
  • Over 200 different mutations in HGD have been associated with the disease.
  • Nitisinone, a drug that inhibits an enzyme upstream of the metabolic blockage, is currently the only approved treatment. It can reduce homogentisic acid levels but does not stop ochronosis from progressing.
  • More research is needed to better understand ochronosis and develop therapies that can prevent or reverse it.

“This primer provides a valuable resource by compiling the latest knowledge on the genetics, pathophysiology, clinical manifestations, diagnosis, and treatment of alkaptonuria,” said Nick Sireau, co-author of the primer and Chair of the AKU Society. “We hope it will raise awareness of this debilitating orphan disease and stimulate further research into its fundamental defect.”

The full primer is available at

The PrimeViewer can be accessed here:

About Nature Reviews Disease Primers:

Nature Reviews Disease Primers is an online publication from Nature Reviews that provides overviews of current research into major disease areas written by leading experts. The primers integrate insights into disease mechanisms with clinical manifestations and treatment.

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