Figura. Resonancia magnética de cráneo: a) Imagen axial FLAIR en T2 del cerebro con hiperintensidad de señal en la sustancia blanca periauricular e hipointensidad de señal en los ganglios basales; b) Imagen axial en T2 (FSE) con cambios en la intensidad de la señal en la sustancia blanca en la corona radiada frontoparietal y atrofia generalizada cortical y subcortical.
Neuronal ceroid lipofuscinosis. Type 6 late infantile variant in two compound heterozygous siblings with novel mutations
Introduction. There are 14 forms of lipofuscinosis, among them type 6 in its late childhood form is found, it starts between three and eight years with epilepsy, motor disorders, myoclonus, dysarthria, ataxia and neurological regression associated with vision loss and motor skills, and early death. It occurs from mutations in the CLN6 gene, most patients have homozygote variants associated with consanguinity, and rarely, with compound heterozygote variants.
Case report. Siblings, started at 4 and 5 years each, with unstable gear, frequent falls and difficult running. Subsequently, loss of gait, myoclonus, dysphagia, and hallucinations. On physical examination, present optic nerve atrophy, Babinski and trunk ataxia. Electroencephalogram with widespread slow wave bursts during non-REM sleep, non photoparoxystic response, MRI with periventricular white substance hyperintensity, cerebellar atrophy and cortical. Panel of lipofuscinosis report two mutations, c.552del and c.244G>C, not described previously, in both patients. The mother was the carrier of the 552 deletion and the father and paternal grandmother of the G>C substitution (Gly82Arg).
Conclusions. Differential diagnosis in neuroregression disorders is difficult because clinical signs are nonspecific, like many other neurodegenerative disorders with progressive myoclonic epilepsy. We report the clinical findings in two Mexican siblings with the late childhood variant of CLN6 with two new heterozygote mutations that contribute to the knowledge of mutations in the Mexican population and point out the relevance of performing next-generation genetic sequencing studies which will allow a better genetic counseling practice.
Key words. Ataxia. CLN6 gene. Lipofuscinosis. Lysosomal diseases. Neuroregression. Progressive epilepsy.