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Description
Histidinemia is an inherited condition characterized by elevated levels of histidine in blood, urine, and the fluid that surrounds the brain and spinal cord (cerebrospinal fluid). Histidine is an amino acid
that acts as a building block for many different proteins.
In most cases, histidinemia does not cause health problems. Most people with elevated histidine levels are unaware that they have this condition. Rarely, people with histidinemia have intellectual disabilities, learning disabilities, or behavioral problems. Having a medical complication during or soon after birth might increase the risk of developmental problems in people with histidinemia.
Frequency
Since many people who have histidinemia do not have signs and symptoms, it is hard to know exactly how many people have the condition. The condition appears to be more common among people of Japanese descent and among the French Canadian population in Quebec, Canada.
Causes
Histidinemia is caused by variants (also called mutations) in the HAL gene, which provides instructions for making an enzyme called histidase. Histidase breaks down histidine that the body gets from food. Histidase is active (expressed) primarily in the liver
and the skin
.
HAL gene variants impair the enzyme's ability to break down histidine, which causes histidine to build up in the blood, urine, and cerebrospinal fluid.
Inheritance
This condition is typically inherited in an autosomal recessive pattern
, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene.
Other Names for This Condition
- HAL deficiency
- HIS deficiency
- Histidase deficiency
- Histidine ammonia-lyase deficiency
- Histidinuria
- Hyperhistidinemia
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Patient Support and Advocacy Resources
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
References
- Brosco JP, Sanders LM, Dharia R, Guez G, Feudtner C. The lure of treatment: expanded newborn screening and the curious case of histidinemia. Pediatrics. 2010 Mar;125(3):417-9. doi: 10.1542/peds.2009-2060. Epub 2010 Feb 15. No abstract available. Citation on PubMed
- Brosnan ME, Brosnan JT. Histidine Metabolism and Function. J Nutr. 2020 Oct 1;150(Suppl 1):2570S-2575S. doi: 10.1093/jn/nxaa079. Citation on PubMed
- Ishikawa M. Developmental disorders in histidinemia--follow-up study of language development in histidinemia. Acta Paediatr Jpn. 1987 Apr;29(2):224-8. doi: 10.1111/j.1442-200x.1987.tb00037.x. No abstract available. Citation on PubMed
- Kawai Y, Moriyama A, Asai K, Coleman-Campbell CM, Sumi S, Morishita H, Suchi M. Molecular characterization of histidinemia: identification of four missense mutations in the histidase gene. Hum Genet. 2005 Apr;116(5):340-6. doi: 10.1007/s00439-004-1232-5. Epub 2005 Jan 27. Citation on PubMed
- Kessler AT, Raja A. Biochemistry, Histidine. 2023 Jul 30. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK538201/ Citation on PubMed
- Lam WK, Cleary MA, Wraith JE, Walter JH. Histidinaemia: a benign metabolic disorder. Arch Dis Child. 1996 Apr;74(4):343-6. doi: 10.1136/adc.74.4.343. Citation on PubMed
- Levy HL, Shih VE, Madigan PM. Routine newborn screening for histidinemia. Clinical and biochemical results. N Engl J Med. 1974 Dec 5;291(23):1214-9. doi: 10.1056/NEJM197412052912303. No abstract available. Citation on PubMed
- Taylor RG, Levy HL, McInnes RR. Histidase and histidinemia. Clinical and molecular considerations. Mol Biol Med. 1991 Feb;8(1):101-16. Citation on PubMed
- Virmani K, Widhalm K. Histidinemia: a biochemical variant or a disease? J Am Coll Nutr. 1993 Apr;12(2):115-24. doi: 10.1080/07315724.1993.10718291. Citation on PubMed
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