Histidinemia: what is it, causes, symptoms, treatment, prognosis

What is histidinemia?

Histidinemia Is a rare hereditary metabolic disorder characterized by a deficiency of the histidase enzyme, which is necessary for the metabolism of the amino acid histidine. At the same time, the concentration of histidine increases in the blood. Excess histidine, imidazole, pyruvic acid and other products of imidazole metabolism are excreted in the urine. Most people with histidinemia have no obvious symptoms to indicate that the person has the disorder (i.e., asymptomatic). Histidinemia is inherited in an autosomal recessive manner.

Signs and symptoms

Histidinemia is considered a benign condition. For many years, mental retardation and speech disorders have been associated with histidinemia. However, these data are currently considered incidental and are not associated with a metabolic defect in histidinemia, since reports of follow-up after newborn screening demonstrated that most children with histidinemia do not develop clinical symptoms. However, clinical symptoms have been reported in some patients with histidinemia. To compare this with benign newborn screening results, it has been suggested that histidinemia may be a risk factor for developing central nervous system problems, and that such problems can only develop in unfavorable circumstances during childbirth.

People with histidinemia have elevated blood levels of the amino acid histidine and excessive amounts of histidine, imidazole, pyruvic acid, and other products of imidazole metabolism in the urine. Most people with the disease adjust to the presence of excess histidine in their blood and do not suffer any side effects.

According to the medical literature, babies born to mothers with histidinemia were asymptomatic.

Causes

Histidinemia is inherited in an autosomal recessive manner. Genetic diseases are determined by two genes, one of which comes from the father and the other from the mother.

Recessive genetic disorders occur when a person inherits an abnormal variant of a gene from each parent. If a person receives one normal gene and one abnormal variant gene for a disease, the person will be a carrier of the disease, but usually asymptomatic. The risk that two carrier parents will both pass on the abnormal gene and therefore infect the baby is 25% with each pregnancy. The likelihood of having a child who will be a carrier, like the parents, is 50% with each pregnancy. The probability for a child to receive normal genes from both parents is 25%. The risk is the same for men and women.

Researchers believe that the disease is caused by mutations in the human histidase gene (gene HAL).

Affected populations

Histidinemia is one of the most common congenital metabolic errors. Based on newborn screening of more than 20 million babies in several countries, histidinemia is estimated to occur in about one in 11,500 newborns altogether. The disease seems to be most common among people of French Canadian or Japanese descent. According to reports of newborn screening, the disorder affects approximately one in 8,600 newborns in Quebec and one in 9,500 newborns in Japan. The disorder starts at birth and affects males and females equally. Histidinemia is now considered to be predominantly benign.

Diagnostics

Diagnosing a genetic or rare condition can often be challenging. Healthcare professionals typically look at medical history, symptoms, physical signs, and laboratory results to make a diagnosis. Elevated levels of histidine in the blood or urine may confirm the diagnosis of histidinemia.

Standard treatments

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

Genetic counseling can also be helpful for affected individuals and their families. Adjunctive treatment is symptomatic and supportive.

Forecast

The disorder does not affect lifespan. Patients with histidinemia show a good prognosis.

Lilia Khabibulina/ article author