Central sleep apnea and daytime sleepiness in Niemann-Pick type C disease: a report of 2 cases

Abstract

Niemann-Pick disease type C (NPC) is an autosomal recessive hereditary disease in which sphingomyelin and cholesterol are deposited in various organs of the body. The clinical manifestations of NPC include neurologic symptoms and cataplexy; other symptoms related to sleep have seldom been reported. One previous study described various sleep disorders including chronic insomnia, obstructive sleep apnea, restless legs syndrome, and rapid eye movement sleep behavior disorder, thus suggesting that sleep disorders in patients with NPC are more prevalent than previously thought and warrant close attention. Here, we describe sleep disorders in 2 patients with NPC and discuss the clinical characteristics and, for the first time, discuss potential pathogenic mechanisms underlying sleep disorders in such patients.

Citation: Zhang Y, Cheng Y, Li N, et al. Central sleep apnea and daytime sleepiness in Niemann-Pick type C disease: a report of 2 cases. J Clin Sleep Med. 2023;19(2):409-414.

Keywords: Niemann-Pick disease; cataplexy; central sleep apnea; excessive daytime sleepiness; orexin; sleep disorder.

Figure 1. Test results.

(A) Niemann-pick cells (foam cells, indicated by the arrow, original magnification ×100) in the 33-year-old male NPC patient’s bone marrow smear. The nuclei were small and peripherally located with loose chromatin. (B) Genetic test results of the 33-year-old male patient with NPC and his family members. The patient harbored a homozygous mutation of the NPC gene in exon 18 (c.2738G>A, pG913D) that has not been previously reported. (C, D) Polysomnography results for the 33-year-old male patient with NPC. Cessation of airflow without respiratory effort was indicative of CSA (indicated by the red rectangle). Mixed sleep apnea is indicated by the blue rectangle and hypopnea is indicated by the green rectangle. Panel D shows the Cheyne-Stokes respiration noted in polysomnography. CSA = central sleep apnea, NPC = Niemann-Pick type C disease.

Figure 2. EEG of the 6-year-old male patient with NPC.

(A, B) Bilateral and irregular spike-and-slow wave discharges during sleep (indicated by the arrow). EEG = electroencephalogram, NPC = Niemann-Pick type C disease.