The clinical presentation and diagnosis of juvenile neuronal ceroid lipofuscinosis: a prospective national study

Abstract

<h3>Aims</h3> This prospective study performs active surveillance for progressive intellectual and neurological deterioration (PIND) among children in the UK via the British Paediatric Surveillance Unit system. <h3>Methods</h3> Data were obtained between January 1995 and December 2009 via reporting paediatricians. The authors analysed the clinical presentation and mode of diagnosis of PIND cases with juvenile neuronal ceroid lipofuscinosis (JNCL). <h3>Results</h3> 47 JNCL patients had been identified by the study (27 female, 20 male). Median age at first symptom: 5 years 11 months. Median age at presentation to the reporting paediatrician: 7 years 9 months. Presenting symptoms were visual failure 40 (85%), developmental delay/learning difficulties 28 (60%), behavioural problems 17 (36%), seizures 10 (21%), memory loss 8 (17%), extrapyramidal signs 6 (13%) and gait disturbance/ataxia 5 (11%). Seizures and gait disturbance became evident in more cases later. MRI brain imaging was carried out in 18, with atrophy in five and subtle white matter changes in two. EEGs were performed in 2521 had abnormalities, usually slow wave and spike/wave discharges. 35 patients had ERGs: all were abnormal. 31 had VEPs: all were abnormal. <h3>Genetic Results</h3> Out of the 47, 31 had genetic studies that were positive: 30 had CLN3 mutations (24 homozygous and two heterozygous, four not known) and one had CLN5 mutations (compound heterozygote). 19/31 had the characteristic fingerprint or curvilinear inclusions on histological examination of biopsy specimens. Of the 16 who did not have genetic studies, 13 had characteristic histological findings on rectal, skin or muscle biopsy, three had a characteristic clinical picture plus vacuolated lymphocytes. <h3>Conclusion</h3> This population-based study provides helpful information about JNCL. The clinical presentation was quite characteristic, with early visual failure in the majority of cases. Paediatricians saw cases about 2 years after symptoms first developed. MRI scans were abnormal in a minorityhowever, ERG/VEP studies were abnormal in all cases where results were available. An increasing number are diagnosed by DNA studies: this trend is likely to continue, resulting in re-classification of cases by genetic abnormality rather than by clinical/biopsy findings.