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Histidinemia
Disease definition
Histidinemia is a rare metabolic disorder characterized by elevated histidine levels in blood, urine, and cerebrospinal fluid, generally with no clinical repercussions.
ORPHA:2157
Classification level: Disorder- Synonym(s):
- HAL deficiency
- HIS deficiency
- Histidase deficiency
- Histidine ammonia-lyase deficiency
- Histidinuria
- Hyperhistidinemia
- Prevalence: 1-9 / 100 000
- Inheritance: Autosomal recessive
- Age of onset: Infancy, Neonatal
- ICD-10: E70.8
- ICD-11: 5C50.20
- OMIM: 235800
- UMLS: C0220992
- MeSH: C538320
- GARD: 6661
- MedDRA: -
Summary
Epidemiology
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.
Etiology
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).
Diagnostic methods
The disease can be diagnosed with blood and urine tests. Nano optical probe samarium tetracycline can be used. The diagnosis can be confirmed by demonstrating the absence or marked reduction of histidase activity in skin or the absence of urocanic acid in skin.
Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them that there is a 25% risk of having an affected child at each pregnancy.
Management and treatment
Restricting dietary histidine brings the blood histidine level back to normal and eliminates the urinary imidazole metabolites in patients with histidinemia and urocanase deficiency. However, no urgent treatment is required because of the benign nature of this condition.
Prognosis
The life expectancy is not affected. Patients with histidinemia show good prognosis.
A summary on this disease is available in Deutsch (2019) Español (2019) Français (2019) Italiano (2019) Nederlands (2019) Português (2004) Russian (2019, pdf) Suomi (2020, pdf) Hebrew (2020, pdf)
Additional information