• Histidinuria due to a renal tubular defect

Histidinemia is considered a benign condition. For years, mental retardation and speech defects were associated with histidinemia. However, these findings are now considered coincidental and not due to the metabolic defect of histidinemia because several recent newborn screenings demonstrated that the majority of infants with histidinemia do not develop any clinical symptoms (asymptomatic).

Individuals with histidinemia have elevated levels of the amino acid histidine in the blood and excessive amounts of histidine, imidazole pyruvic acid, and other imidazole metabolism products in the urine. Most persons with histidinemia adapt to the presence of excessive histidine in the blood and do not suffer any ill effects.

According to the medical literature, infants born to mothers with histidinemia have exhibited no symptoms.
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Histidinemia is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.

Researchers believe that histidinemia is due to mutations of the human histidase gene (HAL) located on the long arm (q) of chromosome 12 (12q22-q24.1). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 12q22" refers to band 2 on the long arm of chromosome 22. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
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Histidinemia is one of the most common inborn errors of metabolism. Based upon newborn screening of more than 20 million infants in several countries, histidinemia is estimated to occur in about one in 11,500 births overall. The disorder appears to be most prevalent among people of French Canadian or Japanese descent. Based upon newborn screening reports, approximately one in 8,600 infants in Quebec and one in 9,500 infants in Japan are affected by the disorder. The abnormality begins at birth and affects males and females in equal numbers. Histidinemia is now thought to be a primarily benign disorder.
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Diagnosis
In some states in the United States (e.g., New York and Massachusetts) routine screening of newborns for histidinemia was conducted through blood or urine tests. However, newborn screening for histidenemia has been discontinued. A diagnosis of histidinemia may be made based upon increased levels of histidine in the blood or urine.

Treatment
Histidinemia is considered a benign, asymptomatic disorder that does not require treatment. According to the medical literature, therapy consisting of a carefully monitored histidine-restricted diet was once recommended, but is no longer called for.

Genetic counseling may also be of benefit to affected individuals and their families. Other treatment is symptomatic and supportive.
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McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 235800; Last Update:6/11/99.

TEXTBOOKS
Buist NRM, Winter SC. Histidinemia. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:459.

Lyon G, et al., eds. Neurology of Hereditary Metabolic Diseases in Childhood. 2nd ed. New York, NY: McGraw-Hill Companies; 1996:89-91.

Scriver CR, et al., eds. The Metabolic and Molecular Basis of Inherited Disease. 7th Ed. New York, NY; McGraw-Hill Companies, Inc; 1995:1107-23.

Buyce ML., ed. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications; For: The Center for Birth Defects Information Services Inc; 1990: 875.

JOURNAL ARTICLES
Lam WK, et al. Histidinaemia: a benign metabolic disorder. Arch Dis Child. 74;1996:343-6.

Suchi M , et al. Molecular cloning and structural characterization of the human histidase gene (HAL). Genomics. 1995;29:98-104.

Widhalm K, Virmani K. Long-term follow-up of 58 patients with histidinemia treated with a histidine-restricted diet: no effect of therapy. Pediatrics. 1994;94:861-6.

Virmani K, Widhalm K. Histidinemia: a biochemical variant or a disease? J Am Coll Nutr. 1993;12:115-24.

Taylor RG, et al. Localization of histidase to human chromosome region 12q22-q24.1 and mouse chromosome region 10c2-d1. Cytogenet Cell Genet. 56;1991:178-81.

Taylor RG, et al. Molecular characterization of histidase cdnas, and sublocalization of the human histidase gene to 12q22-23, and the mouse gene to 10c2-d1. Am J Hum Genet. 45;1989:A164.

Lemieux B, et al. Newborn urine screening experience with over one million infants in the Quebec network of genetic medicine. J Inherit Metab Dis. 11;1988:45-55.

Dyme IZ, et al. Histidinemia. A case of resolution of myoclonic seizures after treatment with a low-histidine diet. Am J Dis Child. 1983;137:256-8.

Scriver CR, et al. Histidinaemia. Part I: reconciling retrospective and prospective findings. Journal Inherited Metab Dis. 1983;6:51-3.

Rosenmann A, et al. Histidinaemia. Part II: impact; a retrospective study. Journal Inherited Metab Dis. 1983;6:54-7.

Coulombe JT, et al. Histidinaemia. Part III: impact; a prospective study. Journal Inherited Metab Dis. 1983;6:58-61.

Snyderman SE, et al. The nutritional therapy of histidinemia. J Pediatr. 1979;95:712-5.

INTERNET:
Histidinemia
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