Introduction
Histidinemia is a very rare hereditary metabolic disorder that is characterized by a lack of the enzyme histidase, which is required for the amino acid histidine metabolism. Most individuals with histidinemia have no obvious symptoms that indicate that a person has this disorder (asymptomatic). Histidine concentrations in the blood are elevated. Histidine, imidazole pyruvic acid, and other imidazole metabolism products are excreted in large quantities in the urine. Histidinemia is the most common inborn error of human metabolism that occurs in the range of 1:8000 in Japan and 1:37,000 in Sweden.
What Is Histidinemia?
Histidinemia is also called histidinuria. It was first described by H. Ghadimi in 1961. It was first detected during newborns' screening for phenylketonuria when urinary imidazole pyruvate produced a false-positive color reaction in the ferric chloride test for urinary phenylpyruvate. Histidinemia is a condition that characterizes elevated blood levels of the amino acid histidine, which is a building block of most proteins. The shortage of the enzyme that breaks down histidine causes histidinemia. No health problems are caused by histidinemia, and many people with histidinemia are not aware that they are suffering from this condition. However, the risk factors, like other medical complications during or soon after birth, along with histidinemia, can increase a person's chances of developing behavioral problems, intellectual disability, or learning disorders. Histidinemia is inherited in an autosomal recessive pattern. Both the copies of the gene in each cell have mutations, and the parents of each individual with an autosomal recessive gene carry one copy of the mutated gene without displaying any symptoms of the condition. Other names for this condition are HAL (histidine ammonia-lyase) deficiency, HIS deficiency, histidase deficiency, and hyperhistidinemia.
What Are the Signs and Symptoms of Histidinemia?
Histidinemia is a benign condition. The signs and symptoms are speech disorders, and intellectual disability is associated with histidinemia. The findings are coincidental. They are not due to the metabolic defect of histidinemia. Clinical symptoms have been reported in a few patients with histidinemia. The benign findings from newborn screening have been found in some patients with histidinemia. Histidinemia has been suggested to be a risk factor for developing central nervous system problems. These problems might develop in unfavorable conditions, such as an abnormal perinatal event. Few patients with histidinemia can have speech abnormalities or be mentally retarded. However, histidinemia can affect speech and intelligence.
What Are the Causes of Histidinemia?
A mutation in the HLA gene causes histidinemia. The HLA gene provides instructions for making the enzyme histidase. Histidase is primarily present in the skin and the liver. Histidase breaks down histidine into a molecule called urocanic acid. The gene mutations in the HLA gene result in the production of a histidase enzyme incapable of breaking down histidine, resulting in elevated levels of histidine in urine and blood. However, the increased levels of histidine do not appear to have a negative effect on the body.
What Is the Pathophysiology of Histidinemia?
Histidinemia results from a deficiency of L-histidine ammonia-lyase, which results in the accumulation of histidine and its metabolites in the urine, blood, and cerebrospinal fluid and a deficiency of urocanic acid. The enzyme activity is undetected in the liver as well as some other tissues but may be normal in the skin.
How Is Histidinemia Diagnosed?
The diagnosis is based on the urine level and elevated plasma level of histidine. Other diagnostic procedures include enzyme determination in skin biopsy, serum histidine determination, and measurement of the urocanate concentration in the sweat. Histidase is present only in the liver and skin. Therefore, urocanate is a normal constituent of sweat.
How Is Histidinemia Treated?
Dietary treatment by histidine restriction corrects the biochemical abnormality. A study shows that low-histidine diets have been successfully shown to reduce blood histidine concentration. However, the treatment is not indicated in most of the patients that are asymptomatic. Genetic counseling may also be beneficial to the affected individual and their families.
Conclusion
Histidinemia is a rare metabolic condition. Histidine levels in the urine, blood, and cerebrospinal fluid are high in histidinemia. Most persons with elevated histidine levels are not aware that they have histidinemia, which typically causes no health problems. Histidinemia results from defects in histidine ammonia-lyase (EC 4.3.1.3) or histidinase. It catalyzes the irreversible non-oxidative deamination of histidine to urocanic acid.
