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Published on: April 4, 2018
Attenuated variants of Lesch-Nyhan disease
H A Jinnah1, Irene Ceballos-Picot, Rosa J Torres
1Department of Neurology and Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA. hjinnah@emory.edu
Brain : a Journal of Neurology
|February 24, 2010
Summary
Lesch-Nyhan disease variants show a spectrum of neurological issues, from mild motor problems to cognitive and behavioral changes, with uric acid overproduction common. Understanding this range aids diagnosis and pathogenesis insights.
Area of Science:
- Neurogenetics
- Metabolic Disorders
Background:
- Lesch-Nyhan disease is a neurogenetic disorder due to hypoxanthine-guanine phosphoribosyltransferase deficiency.
- Classic Lesch-Nyhan disease presents with uric acid overproduction, dystonia, cognitive disability, and self-injurious behavior.
- Variant forms exhibit milder or absent clinical features.
Purpose of the Study:
- To investigate the neurological manifestations in a large cohort of Lesch-Nyhan disease variants.
- To define the clinical spectrum of hypoxanthine-guanine phosphoribosyltransferase deficiency.
Main Methods:
- Prospective, multi-center international study of 46 patients with Lesch-Nyhan disease variants.
- Comprehensive review of 78 prior reports (127 variants).
- Evaluation of motor, cognitive, and behavioral abnormalities.
Main Results:
- All patients had uric acid overproduction.
- 91% exhibited motor abnormalities; 67% had cognitive impairment (never severe).
- Self-injurious behaviors were absent, but maladaptive behaviors were common; 3 patients had no neurological dysfunction.
Conclusions:
- Lesch-Nyhan disease variants present a spectrum from classic disease to asymptomatic hyperuricemia.
- Recognizing this spectrum is crucial for understanding pathogenesis and diagnosis.
- Neurological dysfunction varies significantly among patients with hypoxanthine-guanine phosphoribosyltransferase deficiency.
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