Hyperuricosuria

Abstract: Urolithiasis in pediatric patients has been perceived as uncommon, and the appropriate evaluation and management have been controversial. To determine the clinical characteristics, types of stone problems, and outcomes of pediatric patients with urolithiasis encountered in a referral center, we retrospectively assessed 221 patients (113 girls and 108 boys) with urolithiasis examined at the Mayo Clinic between 1965 and 1987. The median age at onset of symptoms was 11 6 / 12 years among the female patients and 10 6 / 12 years among the male patients. Analysis of stone constituents in 122 patients showed the proportion of calcium oxalate (44.7%), calcium phosphate (23.6%), and cystine (8.1%) stones to be similar in all age-groups. Overall, struvite stones were found in 17.1% and uric acid stones in 1.6% of patients. Conditions that predisposed to metabolic urolithiasis were identified in 115 patients (52%). Hypercalciuria was confirmed in 49 of 145 patients (33.8%) and hyperoxaluria in 25 of 124 (20.2%). Eight of 96 patients had hyperuricosuria, and 5 of 54 had hypocitraturia. Forty-one patients (18.6%) had infection-related stones. Of 66 patients with structural anomalies of the genitourinary tract, 24 (36%) had metabolic abnormalities and 26 (39%) had chronic infection. Among patients with chronic infection, 29% had metabolic abnormalities. Of the 221 patients, 148 (67%) had two or more stones during a mean follow-up of 59 months. Among 140 patients with 12 months or more of follow-up, metabolic activity was present in 31 (22.1%) at the time of most recent examination. Overall, 166 of 221 children (75.1%) were found to have factors that predisposed to urolithiasis. Infected, obstructed, or structurally anomalous urinary tracts seem to be factors permissive for formation of stones and do not obviate the need for careful metabolic assessment in all young patients who form renal stones.

Abstract: Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity is an inborn error of purine metabolism associated with uric acid overproduction and a continuum spectrum of neurological manifestations depending on the degree of the enzymatic deficiency. The prevalence is estimated at 1/380,000 live births in Canada, and 1/235,000 live births in Spain. Uric acid overproduction is present inall HPRT-deficient patients and is associated with lithiasis and gout. Neurological manifestations include severe action dystonia, choreoathetosis, ballismus, cognitive and attention deficit, and self-injurious behaviour. The most severe forms are known as Lesch-Nyhan syndrome (patients are normal at birth and diagnosis can be accomplished when psychomotor delay becomes apparent). Partial HPRT-deficient patients present these symptoms with a different intensity, and in the least severe forms symptoms may be unapparent. Megaloblastic anaemia is also associated with the disease. Inheritance of HPRT deficiency is X-linked recessive, thus males are generally affected and heterozygous female are carriers (usually asymptomatic). Human HPRT is encoded by a single structural gene on the long arm of the X chromosome at Xq26. To date, more than 300 disease-associated mutations in the HPRT1 gene have been identified. The diagnosis is based on clinical and biochemical findings (hyperuricemia and hyperuricosuria associated with psychomotor delay), and enzymatic (HPRT activity determination in haemolysate, intact erythrocytes or fibroblasts) and molecular tests. Molecular diagnosis allows faster and more accurate carrier and prenatal diagnosis. Prenatal diagnosis can be performed with amniotic cells obtained by amniocentesis at about 15–18 weeks' gestation, or chorionic villus cells obtained at about 10–12 weeks' gestation. Uric acid overproduction can be managed by allopurinol treatment. Doses must be carefully adjusted to avoid xanthine lithiasis. The lack of precise understanding of the neurological dysfunction has precluded development of useful therapies. Spasticity, when present, and dystonia can be managed with benzodiazepines and gamma-aminobutyric acid inhibitors such as baclofen. Physical rehabilitation, including management of dysarthria and dysphagia, special devices to enable hand control, appropriate walking aids, and a programme of posture management to prevent deformities are recommended. Self-injurious behaviour must be managed by a combination of physical restraints, behavioural and pharmaceutical treatments.