Histidemia, first described by Ghadimi in 1961, is caused by a defect in histidase. The defect results in elevated urinary excretion of histidine and its transamination products, and in high blood histidine. Blood histidine levels in histidinemic patients range from 290 to 1420 microM (normal 70-120 microM). The clinical picture of histidinemia varies from complete normality to severe retardation, with many patients being asymptomatic. No correlation has been found between clinical and biochemical data. Most reported cases have been identified in newborn screening programs. Frequency of histidinemia ranges from 1 in 8000 (Japan) to 1 in 37,000 (Sweden). Histidinemia is inherited as an autosomal recessive trait. Maternal histidinemia is believed to be benign. Studies in animal models have shown similar metabolic changes in animals and humans, but clinical changes differ. Histidinemia may be treated with a low-histidine diet, which reduces elevated histidine levels, although in most cases no improvement of clinical symptoms has been observed.

Objective. There is no general agreement as to whether or not patients with histidinemia should be treated with a histidine-restricted diet because the majority of the patients are asymptomatic. Between April 1969 and December 1986 124 children with histidinemia were detected in the Austrian Neonates Screening Program and they received long-term follow-up. Design. Fifty nine patients were treated with a histidine-restricted diet (35 mg/kg). The follow-up included determining biochemical parameters, physical examination and psychological assessment of 58 treated and 43 untreated patients. After termination of the Screening Program information about the patients' development was obtained through questionnaires and follow-up of 20 patients aged 11 to 17 years. Results. Histidine blood levels decreased after institution of the diet, but rose again after termination of the diet. In the untreated patients histidine levels were highest at 1 year of age, decreasing with age. When the IQ scores of the treated and the untreated group were compared, significantly higher IQ scores were found in the 4-year-old and 6-year-old untreated patients (P < .05). Clinical symptoms were found in 27 patients; treated and untreated patients were equally affected. The clinical observations included speech defects, psychomotor and general retardation, emotional disturbances, recurrent respiratory infections, and miscellaneous symptoms such as atopic dermatitis. Conclusion. We conclude that patients with histidinemia do not benefit from dietary treatment.