Manifestation and diagnosis of NPC disease in Germany

Misdiagnoses and late diagnoses due to difficult diagnostic work-up and variable signs are common in NPC disease. Aims of this study from several neuropediatric and metabolic working groups are the description of typical manifestations of NPC and the evaluation of the screening parameter chitotriosidase in these patients. Between 2003 and 2008 28 patients in the age of 0–38 years were diagnosed. Infantile manifestation was frequent, however pre-school-age or puberty (13/14 years) manifestation was typical in juvenile patients. In 27 patients chitotriosidase activity was elevated about 119–1726 nmol/ml/h, median 538 nmol/ml/h, normal range 20–80 nmol/ml/h. 1 patient had no activity of chitotriosidase. 4 patients were classified as infantile type, 5 as late-infantile type, 17 as juvenile type and 2 as adult type. 50% of the patients had visceral manifestation, whereas in 27% primarily neurological signs were noted. In 23% an affected sibling caused the diagnostic work-up. In children with infantile or late-infantile type muscular hypotonia occurred 3–9 months after visceral manifestation. As first neurological symptoms In juvenile patients vertical gaze abnormalities (3x), seizures (2x), cataplexy (1x), gait abormalities (5x) and significant worsening of school performance (5x) were observed. In the past chitotriosidase-screening was used in children with splenomegaly to identify patients, in whom specific diagnostic tests for Gaucher disease or the group of Niemann-Pick dieases were necessary. Chitoriosidase screening may gives an hint to NPC disease in the diagnostic work-up of patients with vertical gaze palsy, progressive epilepsy, cataplexy, progressive gait disturbances and significant worsening of school performance.