Niemann–Pick C disease in Spain: Clinical spectrum and development of a disability scale

Abstract

Objectives To describe the clinical evolution of Niemann–Pick C disease to identify possible factors involved in the diagnosis and severity of the disease. Methods A clinical database and a severity scale was created to evaluate 45 patients diagnosed with Niemann–Pick type C in the last 28 years in Spain. Results Complete clinical data were obtained from 30 patients, all were confirmed to have mutations in the NPC1 gene. Regarding clinical form, 3 were perinatal, 7 severe infantile, 6 late infantile, 11 juvenile and 3 adult. Biochemical phenotype was classic in 26. Splenomegaly was present in 28 patients (93%) with a wide range of age at detection. The first symptom of neurological disease was clumsiness, followed in 2–4 years by cerebellar signs. Ophthalmoplegia appeared 2–4 years later and became complete 1–2 years after onset. Dysarthria appeared by the time of complete ophthalmoplegia. Diagnosis was made before the onset of neurological signs in patients with the severe infantile form, at the time of onset of cerebellar signs in the late infantile form and complete ophthalmoplegia in late onset forms. Conclusions In our series, splenomegaly is present in 96% of patients, even in late onset forms during the first years of life. Clumsiness in children with otherwise normal motor development precedes the onset of ataxia by 2–4 years in Niemann Pick type C. A disability scale could be useful for monitoring evolution, establishing possible phenotypic correlations and evaluating future therapies.