A Case Report on Isolated Hypotonia and Growth Retardation: Deceptive Presentation of Lesch-Nyhan Syndrome

Abstract

Aims: To report an atypical phenotypic presentation of Lesch-Nyhan syndrome (LNS) revealed by isolated generalised hypotonia and growth retardation in the absence of the classical neurological and behavioural features, and to emphasise the importance of systematic serum uric acid measurement in unexplained hypotonia. Presentation of Case: A 3-year-old boy, born to first-degree consanguineous parents, presented with generalised hypotonia and motor developmental delay that had been present since the age of 8 months, associated with failure to thrive (weight and height at −2 SD). He had no abnormal movements, no self-injurious behaviour, and no behavioural disturbances. Neurological examination revealed severe action dystonia with resting hypotonia, spasticity, hyperreflexia, and bilateral Babinski signs. The presence of sandy urine with orange crystal deposits in the diapers was noted. Serum uric acid was elevated at 380 µmol/L, with hyperuricosuria of 920 mg/24 h. Brain MRI, EEG, and EMG were normal. Erythrocyte HGPRT activity was undetectable, and genetic analysis identified the HPRT1 c.384+1G>A splice-site mutation, confirming the diagnosis. Results: This case illustrates an atypical phenotype of LNS with complete HGPRT deficiency, yet lacking the hallmark self-injurious behaviour. The c.384+1G>A mutation affects a canonical splice donor site, predicting complete loss of enzyme activity. The absence of self-mutilation despite complete enzyme deficiency highlights the variable expressivity of LNS and supports a broader diagnostic approach to unexplained hypotonia in young children. Conclusion: Isolated hypotonia with growth retardation can be the sole initial manifestation of LNS. Measurement of serum uric acid should be systematic in any child with unexplained hypotonia, as early diagnosis enables timely initiation of allopurinol therapy and genetic counselling.