AIM: To describe the cases of Niemann-Pick type C (NP-C) disease in a United Kingdom epidemiological study of progressive intellectual and neurological deterioration in childhood. METHOD: Paediatricians notified cases via the British Paediatric Surveillance Unit between 1997 and 2015. RESULTS: Fifty-three NP-C patients were identified: 29 females, 24 males. Fifteen cases had a systemic presentation (neonatal jaundice and/or hepatosplenomegaly). Thirty-eight had a neurological onset, the commonest presenting symptom being gait disturbance/ataxia (29 cases, 76%). Forty-nine cases eventually had neurological problems, the commonest were school/cognitive difficulties (40, 82%), seizures (33, 67%), dysphagia (20, 41%), dysarthria (18, 37%), cataplexy (17, 35%), and visual deterioration (8, 16%); their commonest abnormal physical signs were vertical supranuclear gaze palsy (35, 71%), hypotonia (19, 39%) and hepatosplenomegaly (19, 39%). The median diagnostic delay in the 38 neurological onset cases was 3 years (range 0.3-12.8). Confirmatory investigations included filipin staining of skin fibroblasts (42 cases), bone marrow examination in 30 (the last in 2011), and increasingly DNA studies, mutations in NP-C1 being found in 20 cases. INTERPRETATION: NP-C should be considered in children with progressive neurological deterioration. Subtle neurological problems combined with a history of prolonged neonatal jaundice and/or hepatosplenomegaly may provide early evidence of the disease.
AIM: To describe the cases of Niemann-Pick type C (NP-C) disease in a United Kingdom epidemiological study of progressive intellectual and neurological deterioration in childhood. METHOD: Paediatricians notified cases via the British Paediatric Surveillance Unit between 1997 and 2015. RESULTS: Fifty-three NP-Cpatients were identified: 29 females, 24 males. Fifteen cases had a systemic presentation (neonatal jaundice and/or hepatosplenomegaly). Thirty-eight had a neurological onset, the commonest presenting symptom being gait disturbance/ataxia (29 cases, 76%). Forty-nine cases eventually had neurological problems, the commonest were school/cognitive difficulties (40, 82%), seizures (33, 67%), dysphagia (20, 41%), dysarthria (18, 37%), cataplexy (17, 35%), and visual deterioration (8, 16%); their commonest abnormal physical signs were vertical supranuclear gaze palsy (35, 71%), hypotonia (19, 39%) and hepatosplenomegaly (19, 39%). The median diagnostic delay in the 38 neurological onset cases was 3 years (range 0.3-12.8). Confirmatory investigations included filipin staining of skin fibroblasts (42 cases), bone marrow examination in 30 (the last in 2011), and increasingly DNA studies, mutations in NP-C1 being found in 20 cases. INTERPRETATION:NP-C should be considered in children with progressive neurological deterioration. Subtle neurological problems combined with a history of prolonged neonatal jaundice and/or hepatosplenomegaly may provide early evidence of the disease.
Authors: Christopher Verity; Anne Marie Winstone; Robert Will; Alison Powell; Peter Baxter; Carlos de Sousa; Paul Gissen; Manju Kurian; John Livingston; Robert McFarland; Suvankar Pal; Michael Pike; Richard Robinson; Evangeline Wassmer; Sameer Zuberi Journal: Arch Dis Child Date: 2018-10-18 Impact factor: 3.791
Authors: María-Jesús Sobrido; Peter Bauer; Tom de Koning; Thomas Klopstock; Yann Nadjar; Marc C Patterson; Matthis Synofzik; Chris J Hendriksz Journal: Orphanet J Rare Dis Date: 2019-01-21 Impact factor: 4.123