The videofluoroscopic swallowing study shows a sustained improvement of dysphagia in children with Niemann–Pick disease type C after therapy with miglustat

Abstract

Niemann-Pick disease type C (NPC) is a rare autosomal recessive lysosomal storage disorder characterized by defective intracellular lipid trafficking, with secondary accumulation of free cholesterol, sphingosine, and glycosphingolipids. NPC is clinically characterized by a wide spectrum of manifestations with progressive visceral and neurological involvement, including dysphagia. Neurological manifestations represent the most debilitating findings. Swallowing impairment is a frequent cause of morbidity and disability in NPC patients and progressive dysphagia may be considered a marker of neurological progression. Recently substrate reduction therapy with miglustat has been proposed for the treatment of neurological manifestations in NPC patients. This observational study reports on the long-term use of miglustat in four pediatric patients with NPC and shows the efficacy of the treatment to improve or prevent dysphagia, and persistence after 3 years of treatment or more. We used a videofluoroscopic analysis of liquid barium swallowing to provide additional information on patterns of impairment of the swallowing mechanism and to detect aspiration. In three patients showing dysphagia and aspiration we observed the improvement of the swallowing function and the sustained absence of barium aspiration in the airways after miglustat treatment, while the patient with normal swallowing function at baseline did not show any deterioration. We suggest that the videofluoroscopic study of swallowing should be routinely used to monitor the effects of treatment on swallowing ability in NPC patients.

Respiratory manifestations in patients with inherited metabolic diseases

“…At present, the substrate reduction therapy with miglustat has been granted marketing authorisation in Europe and several other countries for specific treatment of neurological manifestations of Niemann-Pick disease. An observational study showed the efficacy of long-term treatment with miglustat in four children with Niemann-Pick disease type C to improve or prevent dysphagia and airway aspiration [118], confirming the beneficial effects on neurological disease [139].…”

“…Swallowing function using video fluoroscopy should be monitored closely, particularly in subjects at risk of aspiration in the event of secondary airway aspiration [118].…”

“…A significant increase of forced vital capacity, probably resulting from chest wall impedance improvement to lung expansion, and a decrease of the apnoea/hypopnoea index, Prevention or improvement of dysphagia and airway aspiration (type C) [118] Regression of infiltrates at chest imaging (type B and C) [32,138] Not available …”

New strategies for the treatment of lysosomal storage diseases (Review)

“…In a controlled trial in 29 adult and juvenile NPC patients, Miglustat stabilized neurological disease, with improved horizontal saccadic eye movement, stabilized ambulation, and improved swallowing (54,55). Improved swallowing was also observed in a study on the efficacy of Miglustat in four pediatric patients (56).…”

Lungenbeteiligung bei erwachsenen Patienten mit angeborenen Stoffwechselerkrankungen

“…Infolge der fehlenden normalen NPC2-Proteinexpression in alveolären Makrophagen und einer Anhäufung von cholesterinreichem Surfactant kann es zu einer pulmonalen alveolären Proteinose (PAP) kommen [21]. Die orale Substratreduktionstherapie mit Miglustat, einem Iminozucker, der die intrazelluläre Speicherung von Glucosylceramid senkt, scheint die Dysphagie und Aspiration erfolgreich verhindern zu können, indem sie das neurologische Fortschreiten der Erkrankung verlangsamt oder zum Stillstand bringt [22,23].…”