HPRTmangel

HPRTmangel is the term used in German-language medical literature for hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency, a hereditary metabolic disorder caused by mutations in the HPRT1 gene on the X chromosome. The condition disrupts the purine salvage pathway, leading to decreased recycling of purines and an imbalance of purine metabolism.

Biochemical basis and genetics: HPRT is an enzyme that recycles purines to their nucleotide forms. Deficiency results in reduced HPRT activity, increased de novo purine synthesis, and accumulation of uric acid and purine metabolites. The disorder is typically inherited in an X-linked recessive pattern; affected males are usually more severely affected, while female carriers may be asymptomatic or mildly affected due to X-inactivation.

Clinical features: Classic HPRT deficiency, often described as Lesch-Nyhan syndrome in English-language sources, includes hyperuricemia and uric acid nephrolithiasis, along with pronounced neurobehavioral symptoms such as dystonia, choreoathetosis, and intellectual disability. Self-injurious behavior is a characteristic feature in many patients. A milder spectrum, sometimes referred to as Kelley-Seegmiller syndrome, presents with partial enzyme activity and less severe manifestations.

Diagnostic approach: Diagnosis is based on low or absent HPRT activity in red blood cells or leukocytes, supported by genetic testing for mutations in HPRT1. Laboratory findings commonly show elevated urinary uric acid and uricemia; imaging may be used to assess kidney stones.

Management: There is no cure. Treatment focuses on lowering uric acid levels with medications such as allopurinol, ensuring adequate hydration, and managing complications. Movement disorders and behavioral symptoms require multidisciplinary care, including physical and occupational therapy, protective strategies to prevent self-harm, and supportive therapies.

History and terminology: The condition was first described in the 1960s by Lesch and Nyhan; in German-language texts, HPRT deficiency is frequently referred to as HPRTmangel.