Dados do Trabalho

Título

An atypical presentation of Lesch-Nyhan syndrome mimicking inherited neurotransmitter metabolism defect with a dopa-responsive phenotype.

RESUMO

Case Report:
A 10-month-old Brazilian male infant presented with irritability, generalized hypotonia and global developmental delay since the neonatal period. Since age 4 months, he started with paroxysmal events, tonic hyperextension of upper limbs several times a day. Afterwards, he started having apneic spells, vomiting, and diaphoresis. Examination at age 1 year and 3 months disclosed axial hypotonia, no ability to sit without support, dystonic posture of neck, arms, and legs, along with choreoathetoid movements in hands and feet. CSF analysis and lab tests were unremarkable, including normal serum uric acid levels. As an inherited disorder of monoamine metabolism was suspected, a levodopa trial was started with marked improvement of dystonic and autonomic disturbances. NGS-based multigene panel for movement disorders disclosed the pathogenic missense variant c.233T>C (p.Leu78Pro) in hemizygosity in the HPRT1 gene (Xq26.2-q26.3), establishing the diagnosis of Lesch-Nyhan syndrome (LNS). Five months after the genetic diagnosis, the patient presented with the typical so-called self-injurious behavior.

Discussion:
Although classically considered in the differential diagnosis of early-onset presentation of complex movement disorders, LNS is rarely considered for further diagnostic work-up after normal serum and urinary screening for uric acid levels. Even in the absence of abnormal serum biomarkers and the typical automutilation features, LNS diagnosis must be kept in the diagnostic work-up of highly suggestive neurological phenotypes. This case highlights the importance of performing large NGS-based multigene panels to screen complex phenotypes of suspected inherited neurometabolic disorders, including LNS and inherited disorders of neurotransmitters metabolism. Marked very early-onset autonomic disturbances were present in this patient and presented with a levodopa-responsive pattern, as well as the dystonic involvement.

Final comments:
Infancy or neonatal-onset cases of global developmental delay, generalized hypotonia, early-onset paroxysmal events resembling dystonic posturing, and dysautonomia must include LNS in the diagnostic work-up. Levodopa-responsive cases should aware clinicians about LNS as a differential diagnosis.

Palavras Chave

Lesch-Nyhan Syndrome; Levodopa