Partial Deficiency of Hypoxanthine-Guanine Phosphoribosyltransferase Manifesting as Acute Renal Damage.

Abstract

A 32-year-old man who had had frequent gouty arthritis over the past 17 years, was admitted for acute renal failure. Acute renal failure was improvedrapidly after medication was resumed and the patient was sufficiently hydrated. The hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity in the patient had been reduced to about 30%of the normal control. Therefore we considered that this patient suffered from a partial deficiency ofHPRT.A point mutation ofHPRT gene 68G (guanine) to T (thymine) was detected. This is a mutation that has not been previously reported. Familial analysis indicated that his mother and sister were heterozygotes. (Internal Medicine 37: 945-949, 1998)

Genotype–phenotype correlations in neurogenetics: Lesch-Nyhan disease as a model disorder

“…Careful examination of these exceptions reveals that all involved the use of biochemical assays that may provide misleading results under certain conditions. For example, one mechanism responsible for reduced HGprt enzyme function involves altered affinities towards hypoxanthine, guanine or PRPP (McDonald and Kelley, 1971;Benke et al, 1973;Richardson et al, 1973;Rijksen et al, 1981;Wilson et al, 1983;Snyder et al, 1984;Zanic et al, 1985;Fujimori et al, 1988;Lightfoot et al, 1994;Hikita et al, 1998;Zoref-Shani et al, 2000;Fu and Jinnah, 2012). For such mutants, in vitro assays employing artificially high substrate concentrations may yield high apparent activities, while concentrations of substrates normally available in vivo may result in little or no actual activity.…”

Acute renal failure due to obstructive uric acid stones associated with rotavirus gastroenteritis

“…Uric acid is rather uncommon as a constituent of childhood urolithiasis: uric acid stones occasionally develop in conditions associated with excessive production of uric acid, such as tumor lysis syndrome or lymphoproliferative/myeloproliferative disorders. Rare inborn errors of uric acid metabolism, i.e., complete or partial deficiencies of hypoxanthine-guanine phosphoribosyltransferase (HPRT) enzyme activity, named LeschNyhan syndrome and Kelley-Seegmiller syndrome, respectively [3,4,5], may be complicated by uric acid stones. We describe the first case of a previously healthy child with acute renal failure caused by obstructive uric acid stones of the bilateral pelviureteric junctions associated with rotavirus gastroenteritis.…”

Partial Hypoxanthine Phosphoribosyltransferase Deficiency: Unrecognized Until Adult Ages

“…The substitution described in the case in this issue Cys22Phe [Although the authors designated this position 23, my numbering system does not count the Met corresponding to the initiation codon.] is also located in the side opposite to GMP (7).…”