Lesch-Nyhan disease

Introduction
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By James C Harris MD

In this clinical article, Dr. James C Harris, Director of Developmental Neuropsychiatry in the Departments of Psychiatry and Pediatrics at the Johns Hopkins University School of Medicine reviews Lesch-Nyhan disease, a metabolic disorder resulting from hypoxanthine phosphoribosyltransferase 1 deficiency. This X-linked genetic disorder is characterized by hyperuricemia, intellectual disability, early hypotonia usually with onset of a predominantly dystonic movement disorder by 6 months of age, subsequent dysarthric speech, and compulsive self-injury with self-mutilation along with an extended cognitive/behavioral phenotype. Studies in an Hprt1-deficient mutant mouse model and PET imaging studies have documented dopaminergic dysfunction with basal ganglia involvement. Management of hyperuricemia with allopurinol, dental management, orthopedic management, and use of protective equipment, along with behavioral interventions, is mandatory. Pharmacology targets stabilization of mood and anxiety management. S-adenosylmethionine (SAMe), a physiological intermediate in methylation and transsulfuration, may have beneficial effects in selected patients who can tolerate the drug. Deep brain stimulation has been demonstrated in several case reports and series to reduce self-injury and aggression, and in some to modify dystonia.

Key points:

  • Lesch-Nyhan disease is a metabolic disorder resulting from hypoxanthine phosphoribosyltransferase 1 deficiency.
  • This X-linked genetic disorder is associated with hyperuricemia, intellectual disability, early hypotonia and dystonic movement disorder, dysarthric speech, and compulsive self-injury with self-mutilation.
  • Lesch-Nyhan disease is characterized by an extended behavioral, neurologic, and neurocognitive phenotype.
  • Studies in an HPRT1-deficient mutant mouse model and PET imaging studies have documented dopaminergic dysfunction.
  • Management of hyperuricemia with allopurinol, dental management, orthopedic management, and use of protective equipment, along with behavioral interventions, is mandatory.

 

In This Article

Introduction
Historical note and nomenclature
Clinical manifestations
Clinical vignette
Etiology
Pathogenesis and pathophysiology
Epidemiology
Prevention
Differential diagnosis
Diagnostic workup
Prognosis and complications
Management
Pregnancy
Anesthesia
References cited
Contributors