Abstract
BackgroundNiemann-Pick type C (NP-C) is a rare autosomal recessive progressive neurodegenerative disorder caused by mutations in the NP-C 1 or 2 gene. Besides visceral symptoms, presentation in adolescent and adult onset variants is often with neurological symptoms. The most frequently reported presenting symptoms of NP-C in adulthood are psychiatric symptoms (38 %), cognitive decline (23 %) and ataxia (20 %). Myoclonus can be present, but its value in early diagnosis and the evolving clinical phenotype in NP-C is unclear. In this paper we present eight Dutch cases of NP-C of whom five with myoclonus.MethodsEight patients with genetically confirmed NP-C were recruited from two Dutch University Medical Centers. A structured interview and neuropsychological tests (for working and verbal memory, attention and emotion recognition) were performed. Movement disorders were assessed using a standardized video protocol. Quality of life was evaluated by questionnaires (Rand-36, SIP-68, HAQ). In four of the five patients with myoclonic jerks simultaneous EEG with EMG was performed.ResultsA movement disorder was the initial neurological symptom in six patients: three with myoclonus and three with ataxia. Two others presented with psychosis. Four experienced cognitive deficits early in the course of the disease. Patients showed cognitive deficits in all investigated domains. Five patients showed myoclonic jerks, including negative myoclonus. In all registered patients EEG-EMG coherence analysis and/or back-averaging proved a cortical origin of myoclonus. Patients with more severe movement disorders experienced significantly more physical disabilities.ConclusionsPresenting neurological symptoms of NP-C include movement disorders, psychosis and cognitive deficits. At current neurological examination movement disorders were seen in all patients. The incidence of myoclonus in our cohort was considerably higher (63 %) than in previous publications and it was the presenting symptom in 38 %. A cortical origin of myoclonus was demonstrated. Our data suggest that myoclonus may be overlooked in patients with NP-C. All patients scored significantly lower on physical domains of HRQoL. Symptomatic treatment of movement disorders may improve physical functioning and subsequently HRQoL.
Highlights
Niemann-Pick type C (NP-C) is a rare autosomal recessive progressive neurodegenerative disorder caused by mutations in the NP-C 1 or 2 gene
Lipid storage products accumulate in many organs including the brain, resulting in cerebral degeneration with progressive neurological symptoms, cognitive decline and psychiatric symptoms
Early- and late- infantile NP-C (0–6 years), juvenile NP-C (6–15 years) and adolescent/adult NP-C (>15 years) can occur and patients mainly present with neurological symptoms, visceral symptoms, in particular in children occur [2, 3]
Summary
Niemann-Pick type C (NP-C) is a rare autosomal recessive progressive neurodegenerative disorder caused by mutations in the NP-C 1 or 2 gene. Presentation in adolescent and adult onset variants is often with neurological symptoms. Niemann-Pick type C (NP-C) is a rare autosomal recessive neurodegenerative disorder with an estimated incidence of 1 per 120.000 live births [1]. Lipid storage products accumulate in many organs including the brain, resulting in cerebral degeneration with progressive neurological symptoms, cognitive decline and psychiatric symptoms. Early- and late- infantile NP-C (0–6 years), juvenile NP-C (6–15 years) and adolescent/adult NP-C (>15 years) can occur and patients mainly present with neurological symptoms, visceral symptoms, in particular in children occur [2, 3]
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