Clinical Features of Patients With the "Partial" Deficiency of the X-Linked Uricaciduria Enzyme

Greene, M. Claire

doi:10.1001/archinte.1972.03650020023005

Arch Intern Med

1972

DOI: 10.1001/archinte.1972.03650020023005

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Clinical Features of Patients With the "Partial" Deficiency of the X-Linked Uricaciduria Enzyme

M. Claire Greene¹

Abstract: Patients with gout associated with "partial" deficiency of hypoxanthine-guanine phosphoribosyltransferase have clinically distinctive findings. Since the disorder is inherited as an X-linked recessive trait, all 21

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Cited by 26 publications

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“…The levels of HPRT activity in Lesch-Nyhan individuals vary from zero to a few per cent of normal. Although some studies have reported a correlation between the extent of the en7yme deficiency and the severity of neurologic dysfunction (GREENE, 1972: SEEGMILLER. 1976).…”

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confidence: 99%

MONOAMINE OXIDASE ACTIVITY IN NORMAL and LESCH‐NYHAN FIBROBLASTS

Edelstein

Castiglione

Breakefield

1978

Journal of Neurochemistry

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Monoamine oxidase ( M A O ) activity was studied in cultured skin fibroblasts from 10 Lesch-Nyhan patients. a Lesch~ Nyhan tariant and 11 controls matched for age. sex and race. Activity (predominantly type A) was measured in cell homogenates using tryptamine as the substrate. For each line activity varied with the conditions of culture. Activity increased 3-10 fold as cultures went from logarithmic to stationary phase of growth. When cultures were confluent. activity was lowered by frequent feedings or the use of fresh medium and serum. Activity for each line remained fairly stable during successive passages. but rose 3-8 fold as cultures became senescent. When comparing activity between control and Lesch-Nyhan lines. cells were cultured under standardized conditions. The mean value of M A 0 activity in Lesch-Nyhan lines was approximately one fourth of the mean acticity in control lines ( P i 0.012). In the control population. the distribution of activity appeared to be bimodal. Activities in the Lesch-Nyhan lines fell completely within the lower portion of the control distribution. Cells from a Lesch-Nyhan patient who lacked several of the neurologic symptoms of the disease (including self-mutilation) had an M A 0 activity 6 fold greater than the control mean. although his hypoxanthine phosphoribosyltransferase activity was < 3",, of control levels.It appears that: ( I ) M A 0 actility is low in fibroblasts from typical Lesch-Nyhan patients: (2) the severity of neurologic symptoms may be correlated with levels of M A 0 activity: and (3) some interaction between purine and catecholamine metabolism can affect nerve function.

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mentioning

confidence: 99%

MONOAMINE OXIDASE ACTIVITY IN NORMAL and LESCH‐NYHAN FIBROBLASTS

Edelstein

Castiglione

Breakefield

1978

Journal of Neurochemistry

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Biochemistry of the X-Linked Uric Aciduria—Enzyme Defect and Its Genetic Variants

Kelley¹

1972

Arch Intern Med

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Further Studies of the Enzyme Composition of Mutant Cells in X-Linked Uric Aciduria

Sweetman

Nyhan

1972

Arch Intern Med

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Assay procedures have been developed for the determination of hypoxanthine guanine phosphoribosyltransferase (HGPRT) and adenine phosphoribosyltransferase (APRT) activity in erythrocytes and for HGPRT and inosinic acid dehydrogenase activity in fibroblasts. In normal erythrocytes the mean activity for HGPRT using hypoxanthine as substrate was 39.09 m\g=m\mols/hr/\g=m\lof cells. The mean value for patients with the Lesch-Nyhan syndrome was 0.003 m\g=m\mols/hr/\g=m\l. Nearly all of the obligate heterozygotes studied had normal levels of HGPRT activity in both erythrocytes and fibroblasts. The normal erythrocyte mean level of APRT activity was 23.56 m\g=m\mols/hr/\g=m\l.All subjects with complete or partial deficiency of HGPRT and heterozygotes had elevated APRT activity.There were no differences among the inosinic acid dehydrogenase (IMPDH) activities of fibroblasts from subjects who were normal, HGPRT-deficient, or hyperuricemic without HGPRT deficiency.The syndrome described by Lesch and Nyhan' consists clinically of mental retardation, athetoid cerebral palsy, and aggressive, compulsive be¬ havior most dramatically character¬ ized by self-mutilation.2 This is an in¬ herited metabolic disease. The locus for the mutant gene is on the X chro¬ mosome.3 It was shown by Seegmiller et al4 that the primary expression of the mutant gene is to determine the activity of the enzyme hypoxanthine guanine phosphoribosyltransferase (HGPRT). Summaries of experience in their laboratory with the enzyme and its defects in the erythrocyte and in the fibroblasts have been presented by Kelley.5·6 It is the purpose of this report to describe our experience with the activity of HGPRT and other en¬ zymes of purine metabolism in con¬ trol individuals and in patients with disorders of purine metabolism.The methods employed for the as¬ say of HGPRT were different from those previously described. Levels of activity of HGPRT have been deter¬ mined using both hypoxanthine and guanine as substrates. Adenine phosphoribosyltransferase (APRT) activity has also been determined using similar methodology. Assess¬ ment of these activities has been car¬ ried out in erythrocytes of control in¬ dividuals and in patients with the Lesch-Nyhan syndrome, in whom the erythrocyte activity of HGPRT is vir¬ tually absent. Erythrocytes have also been studied in patients with partial deficiency of HGPRT in whom quite a different clinical syndrome has been observed.7 8 Patients described by Kogut and colleagues7 had 5% of normal activity of HGPRT and suffered from urinary tract stone disease in child¬ hood. There were no central nervous system abnormalities. We have also studied women who were obligate hétérozygotes and patients with hy¬ peruricemia of unknown cause. The activity of HGPRT has also been de¬ termined using hypoxanthine as sub¬ strate in fibroblasts in cell culture from the same populations of sub¬ jects. The activity of inosinic acid dehydrogenase (IMPDH) has also been assayed in fibroblasts cultured from some of these subjects. MethodsThe assays emp...

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Clinical Features of Patients With the "Partial" Deficiency of the X-Linked Uricaciduria Enzyme

Abstract: Patients with gout associated with "partial" deficiency of hypoxanthine-guanine phosphoribosyltransferase have clinically distinctive findings. Since the disorder is inherited as an X-linked recessive trait, all 21

Cited by 26 publications

References 20 publications

MONOAMINE OXIDASE ACTIVITY IN NORMAL and LESCH‐NYHAN FIBROBLASTS

MONOAMINE OXIDASE ACTIVITY IN NORMAL and LESCH‐NYHAN FIBROBLASTS

Biochemistry of the X-Linked Uric Aciduria—Enzyme Defect and Its Genetic Variants

Further Studies of the Enzyme Composition of Mutant Cells in X-Linked Uric Aciduria

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