Tyrosinemia, Type III / Hawkinsinuria (HPD)
Tyrosinemia, type III is caused by pathogenic variants in the HPD gene and is inherited in an autosomal recessive manner. This disorder has a childhood onset and clinical symptoms include seizures, intellectual disability, severe speech delay, intermittent ataxia, hyperactivity, and unsteady gait. Some patients also present with self-injurious behavior such as hand biting and head banging. Proper management for this disorder involves maintaining a tyrosine and phenylalanine-restricted diet, which allows for a normal life expectancy. Some heterozygous variants in the HPD gene cause an autosomal dominant disorder known as hawkinsinuria, which can manifest symptoms such as failure to thrive and metabolic acidosis that resolve in infancy. Some individuals may also present with unclear hepatopathy and renal tubular acidosis. As the two phenotypes are caused by different types of mutations, the expected phenotype can be predicted based on the inherited pathogenic variant.
For information about carrier frequency and residual risk, please see the residual risk table.