Purines are key components of cellular energy systems (eg, ATP, NAD), signaling (eg, GTP, cAMP, cGMP), and, along with pyrimidines, RNA and DNA production.
Purines may be synthesized de novo or recycled by a salvage pathway from normal catabolism.
The end product of complete catabolism of purines is uric acid.
In addition to purine salvage disorders, purine metabolism disorders (see also table Purine Metabolism Disorders) include
See also Approach to the Patient With a Suspected Inherited Disorder of Metabolism and testing for suspected inherited disorders of metabolism.
Синдром Леша-Найхана
Lesch-Nyhan syndrome is a rare X-linked recessive disorder caused by deficiency of hypoxanthine-guanine phosphoribosyl transferase (HPRT); degree of deficiency (and hence manifestations) varies with the specific mutation. HPRT deficiency results in failure of the salvage pathway for hypoxanthine and guanine. These purines are instead degraded to uric acid. Additionally, a decrease in inositol monophosphate and guanosyl monophosphate leads to an increase in conversion of 5-phosphoribosyl-1-pyrophosphate (PRPP) to 5-phosphoribosylamine, which further exacerbates uric acid overproduction. Hyperuricemia predisposes to gout and its complications. Patients also have a number of cognitive and behavioral dysfunctions, etiology of which is unclear; they do not seem related to uric acid.
The disorder usually manifests between 3 months and 12 months of age with the appearance of orange, sandy precipitate (xanthine) in the urine; it progresses to central nervous system involvement with intellectual disability, spastic cerebral palsy, involuntary movements, and self-mutilating behavior (particularly biting). Later, chronic hyperuricemia causes symptoms of gout (eg, urolithiasis, nephropathy, gouty arthritis, tophi).
Diagnosis of Lesch-Nyhan syndrome is suggested by the combination of dystonia, intellectual disability, and self-mutilation. Serum uric acid levels are usually elevated, but confirmation by DNA analysis is done.
Central nervous system dysfunction has no known treatment; management is supportive. Self-mutilation may require physical restraint, dental extraction, and sometimes pharmacotherapy; a variety of medications has been used. Hyperuricemia is treated with a low-purine diet (eg, avoiding organ meats, beans, sardines) and allopurinol, a xanthine oxidase inhibitor (the last enzyme in the purine catabolic pathway). Allopurinol prevents conversion of accumulated hypoxanthine to uric acid; because hypoxanthine is highly soluble, it is excreted.
Дефіцит аденінфосфорибозилтрансферази
Adenine phosphoribosyltransferase deficiency is a rare autosomal recessive disorder that results in the inability to salvage adenine for purine synthesis. Accumulated adenine is oxidized to 2,8-dihyroxyadenine, which precipitates in the urinary tract, causing problems similar to those of uric acid nephropathy (eg, renal colic, frequent infections, and, if diagnosed late, renal failure). Onset can occur at any age.
Diagnosis of adenine phosphoribosyltransferase deficiency is by detecting elevated levels of 2,8-dihyroxyadenine, 8-hyroxyadenine, and adenine in urine and is confirmed by DNA analysis; serum uric acid is normal.
Treatment of adenine phosphoribosyltransferase deficiency is with dietary purine restriction, high fluid intake, and avoidance of urine alkalinization. Allopurinol can prevent oxidation of adenine; renal transplantation may be needed for end-stage renal disease.
Додаткова інформація
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
Online Mendelian Inheritance in Man (OMIM) database: Complete gene, molecular, and chromosomal location information
