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Synonym(s) HAL deficiency
HIS deficiency
Histidase deficiency
Histidine ammonia-lyase deficiency
Prevalence 1-9 / 100 000
Inheritance Autosomal recessive
Age of onset Infancy
  • E70.8
  • C0220992
  • C538320
MedDRA -


Disease definition

Histidinemia is a rare metabolic disorder characterized by elevated histidine levels in blood, urine, and cerebrospinal fluid, generally with no clinical repercussions.


Reported prevalence varies widely from 1/8,600 to 1/180,000, probably as a result of differing screening programs.

Clinical description

Histidinemia is defined biochemically as elevated histidine in blood, urine and cerebrospinal fluid, and decreased levels of the metabolite urocanic acid in blood, urine, and the skin. In most individuals with histidinemia, the condition is clinically silent and considered benign, with no need for treatment or a specific diet. In a small subset of patients with specific events in the neonatal period, such as low oxygen, it has been suggested that histidinemia may contribute to development of intellectual disability, behavioral or learning disorders. Growth is normal in patients with the disorder. Histidinemia is important because in the 1960s and 1970s the condition was unnecessarily added to universal newborn screening before the natural history was fully understood.


Histidinemia is caused by impaired conversion of histidine to urocanic acid via the histidase enzyme. Deficiency in this enzyme is related to mutations in the histidine ammonia-lyase HAL gene (12q22-q24.1).

Genetic counseling

Histidinemia is inherited in an autosomal recessive manner.

Expert reviewer(s)

  • Dr Jeffrey BROSCO

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