Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome (SLC25A15)

Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is an autosomal recessive disorder caused by pathogenic variants in the gene SLC25A15 and is most commonly seen in the Metis from Saskatchewan and in the French Canadian population. Individuals with this disorder can present with symptoms during infancy, but the majority present during adulthood. Symptoms of the infantile form of the disease include lack of energy, refusal to eat, poorly controlled breathing and body temperature, seizures, and comas. Adults with the disorder present with vomiting, lack of energy, coordination difficulties, confusion, and blurred vision after eating high-protein meals or during stressful times. Other common symptoms for either form include learning disabilities and liver dysfunction. The prognosis of the disorder is variable; some affected individuals only have mild neurocognitive impairment while others will continue to progressively worsen despite early detection and metabolic control. It is not currently possible to predict disease severity based on the variants inherited.

For information about carrier frequency and residual risk, please see the residual risk table.

This gene is included on the following panel(s):