A Female Patient with Lesch‐Nyhan Syndrome

Yukawa, Takeo; Akazawa, Hirofumi; Miyake, Yoshihiro; Takahashi, Yūzō; Nagao, Hideo; Takeda, Eiji

doi:10.1111/j.1469-8749.1992.tb11477.x

Cited by 11 publications

(8 citation statements)

References 6 publications

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“…Since Lesch-Nyhan disease is inherited in an X-linked recessive manner, the vast majority of cases are males. However, several manifesting females have been reported (Hooft et al, 1968;Hara et al, 1982;Ogasawara et al, 1989;Van Bogaert et al, 1992;Yukawa et al, 1992;Yamada et al, 1994;Aral et al, 1996;De Gregorio et al, 2000;Inokuchi et al, 2004;De Gregorio et al, 2005;Rinat et al, 2005;Jinnah et al, 2006Jinnah et al, , 2010Sebesta et al, 2008). Eight of the manifesting females had the typical Lesch-Nyhan disease phenotype, and two were milder variants.…”

Section: The Spectrum Of the Clinical Phenotypementioning

confidence: 99%

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

Ceballos-Picot

Torres

et al. 2013

Brain

111

107

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Establishing meaningful relationships between genetic variations and clinical disease is a fundamental goal for all human genetic disorders. However, these genotype-phenotype correlations remain incompletely characterized and sometimes conflicting for many diseases. Lesch-Nyhan disease is an X-linked recessive disorder that is caused by a wide variety of mutations in the HPRT1 gene. The gene encodes hypoxanthine-guanine phosphoribosyl transferase, an enzyme involved in purine metabolism. The fine structure of enzyme has been established by crystallography studies, and its function can be measured with very precise biochemical assays. This rich knowledge of genetic alterations in the gene and their functional effect on its protein product provides a powerful model for exploring factors that influence genotype-phenotype correlations. The present study summarizes 615 known genetic mutations, their influence on the gene product, and their relationship to the clinical phenotype. In general, the results are compatible with the concept that the overall severity of the disease depends on how mutations ultimately influence enzyme activity. However, careful evaluation of exceptions to this concept point to several additional genetic and non-genetic factors that influence genotype-phenotype correlations. These factors are not unique to Lesch-Nyhan disease, and are relevant to most other genetic diseases. The disease therefore serves as a valuable model for understanding the challenges associated with establishing genotype-phenotype correlations for other disorders.

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Section: The Spectrum Of the Clinical Phenotypementioning

confidence: 99%

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

Ceballos-Picot

Torres

et al. 2013

Brain

111

107

View full text Add to dashboard Cite

show abstract

“…Thus, males are generally affected and women are generally asymptomatic carriers. At least five women with Lesch-Nyhan syndrome due to a variety of molecular mechanisms have been described in the literature [ 8 - 15 ]. The prevalence of the disease is estimated to be 1/380,000 live births in Canada [ 16 ], and 1/235,000 live births in Spain.…”

Section: Epidemiologymentioning

confidence: 99%

Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome

Torres

Puig

2007

Orphanet J Rare Dis

235

155

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“…Moreover, laboratory examinations are used to assess the signs and symptoms of LNS, such as the dramatic high levels of uric acid due to absent purine recycling exceeding the normal values of 208-428 μmol/L in male and 155-357 μmol/L in female individuals. The decreased level of the HPRT1 enzyme activity in erythrocytes has been detected with a subsequent increase in the APRT enzyme activity in some patients (Ogasawara et al, 1989;van Bogaert et al, 1992;Yukawa et al, 1992;Yamada et al, 1994;Jinnah et al, 2000;De Gregorio et al, 2005;Rinat et al, 2006). On the other hand, almost all cases showed an increase in serum uric acid levels.…”

Section: Discussionmentioning

confidence: 98%

“…In this study, we report a novel de novo frameshift mutation that led to LNS in a female patient from Saudi Arabia. The HPRT1 deficiency was confirmed based on previously described functional studies (Hara et al, 1982;Ogasawara et al, 1989;van Bogaert et al, 1992;Yukawa et al, 1992;Aral et al, 1996;De Gregorio et al, 2000;Rinat et al, 2006).…”

Section: Introductionmentioning

confidence: 93%

“…Heterozygote female individuals are usually phenotypically normal, and the HPRT1 activity in their hemolysate is commonly normal, whereas heterozygote male individuals are affected ( Torres and Puig, 2007 ). However, rarely, female carriers can be symptomatic, and so far, only 14 female individuals with heterozygous mutations in HPRT1 have been described with full biochemical and clinical manifestations of LNS ( Hooft et al, 1968 ; Hara et al, 1982 ; Ogasawara et al, 1989 ; van Bogaert et al, 1992 ; Yukawa et al, 1992 ; Yamada et al, 1994 ; Aral et al, 1996 ; De Gregorio et al, 2000 ; Jinnah et al, 2006 ; Sebesta et al, 2008 ).…”

Section: Introductionmentioning

confidence: 99%

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Detailed genetic and clinical analysis of a novel de novo variant in HPRT1: Case report of a female patient from Saudi Arabia with Lesch–Nyhan syndrome

Al-Bakheet

AlQudairy²,

Alkhalifah³

et al. 2023

Front. Genet.

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Background: Hypoxanthine-guanine phosphoribosyltransferase (HPRT1) deficiency is an inborn error of purine metabolism responsible for Lesch–Nyhan syndrome (LNS). The disease is inherited in an X-linked recessive manner and predominantly affects male individuals. Female individuals can carry a mutation as heterozygotes, but typically, they are asymptomatic because of the random inactivation of the affected allele. Nevertheless, although rare, heterozygote female individuals may manifest LNS with full characteristics. Herein, we describe a female patient from Saudi Arabia with LNS.Results: The patient (a 4-year-old girl) presented with typical characteristics of the disease, which include global developmental delay, self-mutilation, hyperuricemia, hypotonia, speech delay, spasticity, and seizures. Her general biochemical laboratory results were normal except for high levels of uric acid. The abdominal MRI\MRS, mostly unremarkable, showed bilateral echogenic foci within the renal collecting system. Genetic testing (whole-exome sequencing, iterative variant filtering, segregation analysis, and Sanger sequencing) pointed a novel de novo frameshift variant in HPRT1. X-inactivation assay using HpaII showed the presence of a 100% skewed X chromosome carrying the affected allele. RT-PCR of the cDNA indicated complete loss of the expression of the normal allele.Conclusion: Our study presents a female patient who has a severe case of LNSand found to be the 15th female patient with the disease in the world. The study emphasizethe need for a streamlined protocol that will help an early and accurate diagnosis of female LNS patients to avoid unnecessary interventions that lead to costly patient care.

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A Female Patient with Lesch‐Nyhan Syndrome

Cited by 11 publications

References 6 publications

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

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

Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome

Detailed genetic and clinical analysis of a novel de novo variant in HPRT1: Case report of a female patient from Saudi Arabia with Lesch–Nyhan syndrome

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