Lesch-Nyhan Syndrome: Evidence for Abnormal Adrenergic Function

Rockson, Stanley G.; Stone, Richard A.; Weyden, Martin Van Der; Kelley, William N.

doi:10.1126/science.186.4167.934

Cited by 50 publications

(15 citation statements)

References 21 publications

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“…Group I included subjects who rarely experienced hypotensive episodes with hemodialysis and group II consisted of patients who frequently have hemodialysis hypotension. Both groups of patients exhibited similar early hemodynamic responses to cold pressor tests, and these responses were similar to those previously observed in apparently healthy subjects (16,25). Although conclusions from these results must be tempered by the aforementioned limitations of the cold pressor test, the data suggest that hemodialysis-associated hypotension does not result from defective efferent sympathetic nerves or vascular abnormalities.…”

Section: Discussionsupporting

confidence: 70%

Adrenergic regulation of blood pressure in chronic renal failure.

Lilley¹,

Golden²,

Stone³

1976

J. Clin. Invest.

168

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A B S T R A C T Previous investigations have suggested that significant hypotension during hemodialysis may result from abnormalities of sympathetic nervous system activity. To further evaluate these phenomena, plasma dopamine 8-hydroxylase (D3H) and cold pressor test (proposed indexes of efferent sympathetic nervous system activity) and amyl nitrite inhalation (an index of the entire baroreceptor reflex arc) were studied in two groups of patients: group I, patients exhibiting a mean arterial pressure decrease to less than 70 mm Hg during less than 10% of dialyses; group II (hemodialysis hypotension), patients with a mean arterial pressure decrease to less than 70 mm Hg during more than 90% of dialyses. The groups were similar with respect to plasma renin activity, renin response to ultrafiltration, age, duration of dialysis, nerve conduction velocity, plasma protein concentration, hematocrit, dialysis weight change, resting heart rate, sex, race, blood pressure and heart rate response to cold pressor test, and 1"I-albumin plasma volume. Supine mean arterial pressure was higher in patients with hemodialysis hypotension than in patients without hemodialysis hypotension (group I) both before and after dialysis. Plasma D#3H activity was significantly higher in patients with hemodialysis hypotension (group II) than in group I both before and after dialysis. Amyl nitrite inhalation, expressed as change in AR-R interval/mean arterial pressure decrease, was less in hemodialysis hypotension patients.These results suggest that hemodialysis hypotension may result from a lesion in the baroreceptors, cardiopulmonary receptors, or visceral afferent nerves. Furthermore, elevated mean arterial pressure in patients with hemodialysis hypotension may be neurogenic in origin, as reflected by plasma Dj8H activity, and appears similar to the hypertension that follows baroreceptor deafferentation of experimental animals.

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Section: Discussionsupporting

confidence: 70%

Adrenergic regulation of blood pressure in chronic renal failure.

Lilley¹,

Golden²,

Stone³

1976

J. Clin. Invest.

168

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“…The overresponse of children with Lesch-Nyhan syndrome to emotions of excitement or anger has suggested an excessive adrenergic response to some observers.292 In like manner, the self-mutilation, agitation, and "sham rage" produced by the methylated purines caffeine and theophylline as well as amphetamines furthered this type of speculation.52.228.240 More definitive evidence of an adrenergic overactivity has been provided by Rockson et al,267a who demonstrated a significantly increased activity of the enzyme dopamine-,Bhydroxylase in the plasma of all six patients tested who showed choreoathetosis and self-mutilation, while four less severely affected patients who showed neither of these symptoms despite deficient HPRT enzyme showed dopamine ,B-hydroxylase activities of plasma within the normal range. Since this enzyme is released into the synaptic cleft along with the neurotransmitter norepinephrine, the increased activity of the enzyme in plasma is thought to reflect an increased activity of the sympathetic nervous system.…”

Section: Adrenergic Dysfunctionmentioning

confidence: 92%

Inherited Deficiency of Hypoxanthine-Guanine Phosphoribosyltransferase in X-Linked Uric Aciduria (the Lesch-Nyhan Syndrome and Its Variants)

Seegmiller

1976

Advances in Human Genetics 6

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“…In contrast, NE levels have been reported to be normal or reduced at baseline, and irresponsive to postural changes (Lake and Ziegler 1977;Rockson 1974), or to exposure to cold (Rockson 1974). …”

Section: Discussionmentioning

confidence: 99%

“…Notwithstanding, EPI concentrations have not been assessed in any of the published biochemical studies of LN disease (Rockson 1974;Lake and Ziegler 1977;Silverstein et al 1985;Jankovic et al 1988). In contrast, NE levels have been reported to be normal or reduced at baseline, and irresponsive to postural changes (Lake and Ziegler 1977;Rockson 1974), or to exposure to cold (Rockson 1974).…”

Section: Discussionmentioning

confidence: 99%

Adrenergic and Noradrenergic Plasma Levels in Lesch-Nyhan Disease

Ernst¹,

Zametkin²,

Pascualvaca³

et al. 2000

Neuropsychopharmacology

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Noradrenergic dysfunction and abnormality in monoamine oxidase (MAO) enzyme activity have been reported previously in Lesch-Nyhan (LN) Lesch-Nyhan disease (LN), a rare X-linked recessive disorder of purine synthesis, is characterized by the virtual absence of hypoxanthine guanine phosphoribosyl transferase (HPRT), one of the major enzymes of the salvage pathway of purine synthesis. Although HPRT activity is found in all tissues, highest levels are found in the brain and in the basal ganglia in particular. The human HPRT gene lies on the X chromosome (Xq26-27) and contains nine exons distributed over 40kb of DNA. The majority of the genetic lesions are point mutations, which affect the ability of the enzyme to catalyze the conversion of hypoxanthine and guanine to their respective nucleotides, inosinic acid and guanylic acid. In the absence of HPRT activity, de novo purine synthesis is increased, leading to the overproduction of uric acid. The clinical presentation includes hyperuricemia and a neuropsychiatric syndrome of choreoathetosis, dystonia, and compulsive aggression against self and others

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Lesch-Nyhan Syndrome: Evidence for Abnormal Adrenergic Function

Cited by 50 publications

References 21 publications

Adrenergic regulation of blood pressure in chronic renal failure.

Adrenergic regulation of blood pressure in chronic renal failure.

Inherited Deficiency of Hypoxanthine-Guanine Phosphoribosyltransferase in X-Linked Uric Aciduria (the Lesch-Nyhan Syndrome and Its Variants)

Adrenergic and Noradrenergic Plasma Levels in Lesch-Nyhan Disease

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