Diagnosis and Treatment of the Lesch-Nyhan Syndrome

HPRT Hypoxanthine-guanine phosphoribosyl transferase LND Lesch-Nyhan disease AIM The aims of this study were to identify all people with Lesch-Nyhan disease (LND) born in the UK between 1988 and 2008, and to obtain a clinical profile including age at diagnosis, genetic background, family history, neurological signs, and medications.METHOD Potential participants were contacted through the British Paediatric Neurology Surveillance Unit. Questionnaires were sent to each child's paediatric neurologist or primary consultant. Two purine laboratories provided metabolic information.RESULTS Twenty-three live males with LND in the 0-to 20-year age band and eight live males over the age of 20 years were identified. Thirty-one live people with LND were identified in the UK in 2008, giving a prevalence of 1 in 2 million people. Over the 20 years of study, there was a mean incidence rate of 0.18 per 100 000 live births, range 0 to 0.5.

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“…The incidence of LND often cited internationally is taken from the report of Crawhall et al 12 . from Canada of 1 in 380 000 live births in 1972.…”

Section: Discussionmentioning

confidence: 99%

“…The incidence of LND often cited internationally is taken from the report of Crawhall et al 12 from Canada of 1 in 380 000 live births in 1972. However, in Spain in 2007, Torres and Puig reported an estimated prevalence of 1 in 235 000 live births, although this included all forms of HPRT enzyme deficiency.…”

Section: Discussionmentioning

confidence: 99%

A population study of Lesch-Nyhan disease in the UK

McCarthy¹,

Green²,

Ogunbona

et al. 2010

Developmental Medicine &Amp; Child Neurology

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“…However, data to explain the relation of the accelerated purine synthesis to the central nervous system dysfunction of the L-N syndrome have been difficult to obtain. Hypotheses to explain hyperuricemia and the development of neurologic dysfunction have been examined in detail [10,37,44]. H-G PRT has high activity in fetal brain [1,39], and values rise to the higher values of adult brain shortly after birth [1].…”

Section: Discussionmentioning

confidence: 99%

Adenine and Folic Acid in the Lesch-Nyhan Syndrome

Benke¹,

Herrick²,

Smitten³

et al. 1973

Pediatr Res

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Therapy of identical twin males with the enzyme defect of the Lesch-Nyhan (L-N) syndrome was instituted at 12 hr of age with adenine, 10 mg/kg/24 hr, administered to one twin and folic acid, 15 mg/24 hr, to both. At 4 years of age both twins demonstrate delayed neurologic development and spasticity but are less severely affected than most other patients with this disorder. Administered in subsequent studies to two maternal cousins of the twins who had clinical features of the L-N syndrome and absence of erythrocyte hypoxanthine-guanine phosphoribosyltransferase activity were adenine, 10 mg/kg/24 hr, adenine, 40 mg/kg/24 hr, folic acid, and monosodium glutamate. Low dose adenine had a slight suppressive effect on glycine-1-14 C incorporation into uric acid; high dose adenine had a strong suppressive effect in the second patient. We conclude that the adenine dose chosen for therapy was too low. 2,8-Dihydroxyadenine, a toxic breakdown product of adenine, was detected in the urine at both adenine dose levels. Folic acid and monosodium glutamate in these patients further stimulate accelerated glycine-ll4 C incorporation into uric acid. In vitro transport studies, performed with inverted hamster jejunal preparations, suggest that adenine is largely converted to adenine monophosphate when exposed to the mucosal surface. This may limit the passage of orally administered adenine to the central nervous system in patients. Adenine and purine precursors affect the biochemical pathology of the L-N syndrome, in vivo and in vitro, but therapeutic use of adenine, 10 mg/kg/24 hr, and folic acid started on the 1st day of life did not prevent central nervous system dysfunction. Speculation

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“…Use of allopurinol lowers uric acid levels to normal but does not affect the neurological or behavioural aspect of the disease [7]. often overlooked until late infancy or early childhood when the neurological abnormalities become Case report apparent, even though crystalluria and haematuria may be present in the first months of life [3]. The prognosis is poor; death usually supervenes in the first or second decade of life.…”

Section: Introductionmentioning

confidence: 99%

Oral self‐mutilation by a 17‐month‐old child with Lesch‐Nyhan syndrome

Rashid¹,

Yusuf²

1997

Int J Paed Dentistry

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We report a 17-month-old boy who was a known case of Lesch-Nyhan syndrome and presented with self-inflicted oral ulcerations of his lips and cheeks. He had a normal complement of caries-free deciduous teeth. Initially a conservative approach was planned and a bite plate made, but as a result of poor compliance and persistent ulceration and after consultation with his parents it was decided to extract all deciduous teeth. Introductionpurine metabolism. HPRT catalyses the condensation

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Diagnosis and Treatment of the Lesch-Nyhan Syndrome

Cited by 62 publications

References 42 publications

A population study of Lesch-Nyhan disease in the UK

A population study of Lesch-Nyhan disease in the UK

Adenine and Folic Acid in the Lesch-Nyhan Syndrome

Oral self‐mutilation by a 17‐month‐old child with Lesch‐Nyhan syndrome

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