Case reportLesch Nyhan syndrome: A novel complex mutation in a Tunisian child
Introduction
Lesch Nyhan syndrome (LNS) is an inborn error of purine metabolism, due to the deficient activity of the hypoxanthine–guanine phosphoribosyltransferase (HPRT) enzyme. This defect causes an overproduction of uric acid and a spectrum of neurological and extra neurological features. Phenotypical variability depends on the degree of residual enzymatic activity [1], [2]. LNS is an X-linked recessive disorder, however about 30% of patients present de novo mutations. To date, more than 300 heterogeneous mutations in type and location within the HPRT1 gene have been reported [1], [2], [3]. We report on a Tunisian child with a severe phenotype due to a novel identified complex mutation.
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Case report
A 6-year-old boy, born to 1st degree consanguineous parents, presented to our department with a psychomotor delay. Reactive smiling was acquired at the age of 1 month, no other psychomotor milestones were acquired. His antenatal and perinatal history was uneventful. He had a family history of adult-onset renal failure of unknown etiology in two cousins (Fig. 1). The patient’s mother and siblings were asymptomatic. He had a urinary infection at the age of 2 years, renal ultrasound and retrograde
Discussion
This case illustrates clinically a classic LNS phenotype associating choreic movements, dystonia, compulsive self-injury behavior, mental retardation and uric acid overproduction. The complete defect of HPRT was presumed in our patient, since the enzymatic activity is often undetectable in patients with classic phenotype of LNS [1], [2], [3], [4]. Severity of neurological manifestations in our patient can be explained by the proven correlation between the residual activity of HPRT and the
Conclusion
LNS should be considered in boys with psychomotor delay and movement disorders, even if renal and behavioral features were absent. Molecular diagnosis discloses the genetic heterogeneity of HPRT deficiency. It allows fast and accurate carrier detection and genetic counseling [1], [2].
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