Partial Deficit of Hypoxanthine Guanine Phosphoribosyl Transferase Presenting as Acute Renal Failure

Andrés, Axel; Praga, Manuel; Ruilope, Luís M.; Martínez, Jesús Montenegro; Millet, V. Gutierrez; Bello, I; Rodicio, José L.

doi:10.1159/000184337

Cited by 14 publications

(6 citation statements)

References 8 publications

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“…Similar to other cases of HPRT deficiency complicated by ARF, diuresis was restored in our patient with fluid infusion and furosemide. Despite the significant increase in serum creatinine, renal function recovered promptly after therapy for limiting uric acid overproduction and enhancing its excretion [5,8,17,18].…”

Section: Discussionmentioning

confidence: 99%

Lesch-Nyhan syndrome presenting with acute renal failure in a 3-day-old newborn

2008

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Acute renal failure developed during the first 3 days after birth in a newborn subsequently diagnosed with hypoxanthine-guanine-phosphoribosyl-transferase (HPRT) deficiency. Fluid infusion and allopurinol therapy normalised renal function and serum uric acid levels. Only a few cases of acute renal failure due to acute hyperuricemic nephropathy related to HPRT deficiency have previously been reported in infants, and there are no reported cases in newborns as young as 3 days old.

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Section: Discussionmentioning

confidence: 99%

Lesch-Nyhan syndrome presenting with acute renal failure in a 3-day-old newborn

2008

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“… Clinical features and results of clinical diagnostic testing were collected from prior reports of these same patients (Andres et al 1987; Jinnah et al 2010; Larovere et al 2007; Puig et al 2001) and/or the medical records. Some information was not available for all cases (NA), and some enzyme results were below detectable limits (ND).…”

Section: Figures and Tablesmentioning

confidence: 99%

Mechanisms for phenotypic variation in Lesch–Nyhan disease and its variants

Sampat

Laróvere

et al. 2010

Hum Genet

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Lesch–Nyhan disease is a neurogenetic disorder caused by mutation of the HPRT1 gene on the X chromosome. There is significant variation in the clinical phenotype, with more than 300 different known mutations. There are few studies that have addressed whether similar mutations result in similar phenotypes across different patients because hypoxanthine–guanine phosphoribosyltransferase (HGprt) deficiency is rare, and most mutations are unique or limited to individual families. However, recent studies have revealed multiple unrelated patients with similar mutations, providing an opportunity to examine genotype–phenotype correlations. We found significant variation among the clinical features of 10 patients from 8 unrelated families all carrying a mutation replacing guanine with adenine at base position 143 (c.143G>A) in the HPRT1 gene. This mutation results in replacement of arginine by histidine at amino acid position 48 (p.arg48his) in the HGprt enzyme. Biochemically, the enzyme exhibits reduced thermal integrity, a mechanism that may explain clinical variation. The literature reveals similar clinical variation among other patients with similar mutations, although the variation is relatively minor across the whole population of patients. Identifiable sources of clinical variation include known limitations of clinical ascertainment and mechanisms that affect residual enzyme activity and stability. These results are helpful for understanding genotype–phenotype correlations and discordance and likely are applicable to other neurogenetic disorders where similar variation occurs.

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“…Partial deficiency of HPRT enzyme activity is associated with gouty arthritis, uric acid stones and, rarely, neurological dysfunction [Kelley et al, 1969; Greene, 1972]. Acute renal failure (ARF) is uncommon in those with HPRT deficiency and only a few cases have been described in children [Holland et al, 1983; Batch et al, 1984; Lorentz et al, 1984; Andres et al, 1987; Simmonds et al, 1989; Hidalgo‐Laos et al, 1997]. HPRT mutations have been reviewed in detail by Sculley et al [1992] and Jinnah et al [2000].…”

Section: Introductionmentioning

confidence: 99%

Childhood hyperuricemia and acute renal failure resulting from a missense mutation in the HPRT gene

et al. 2002

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A 6-year-old boy was determined to have partial hypoxanthine phosphoribosyl transferase (HPRT) enzyme deficiency without the phenotypic features of Lesch-Nyhan syndrome. He presented with recurrent acute renal failure (ARF) from hyperuricemia. Treatment with allopurinol prevented further attacks of renal failure. T lymphocyte cultures were used to sequence the HPRT cDNA and a novel single nucleotide substitution at codon 65 in exon 3 was found (193C>T, 65leu>phe). This mutation was confirmed by genomic DNA sequencing and was also detected in his heterozygous, asymptomatic mother and sister. Unlike the cells from patients with classic Lesch-Nyhan syndrome, the in vitro cultures of our patient's T-lymphocytes did not proliferate in the presence of purine analogue 6-thioguanine (TG). This report highlights the unusual occurrence of recurrent ARF in a child with partial HPRT enzyme deficiency. The absence of TG resistance in vitro with this mutation shows that even small alterations in enzyme activity in vivo can result in disease symptoms, in this instance, hyperuricemia sufficient to cause ARF. Atypical HPRT mutations should also be considered in cases of unusual renal failure, because correct diagnosis can allow appropriate treatment, as well as informed genetic counseling.

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Partial Deficit of Hypoxanthine Guanine Phosphoribosyl Transferase Presenting as Acute Renal Failure

Cited by 14 publications

References 8 publications

Lesch-Nyhan syndrome presenting with acute renal failure in a 3-day-old newborn

Lesch-Nyhan syndrome presenting with acute renal failure in a 3-day-old newborn

Mechanisms for phenotypic variation in Lesch–Nyhan disease and its variants

Childhood hyperuricemia and acute renal failure resulting from a missense mutation in the HPRT gene

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