Marked Heterogeneity in Niemann-Pick Disease, Type C

Abstract

Niemann-Pick disease type C (NP-C) is an autosomal recessive lysosomal lipid storage disorder of unknown etiology. Diagnosis of NP-C is based on characteristic clinical findings and reduced fibroblast esterification of LDL-derived cholesterol. We describe three patients who demonstrate the NP-C spectrum of clinical heterogeneity in age of onset, presenting signs, pattern of organ system involvement, and natural history. In addition, electron microscopic analysis of skin biopsy specimens from these patients revealed marked variability in the extent and cellular distribution of intralysosomal storage and was suggestive of the correct diagnosis in only one case. These cases demonstrate both the limitations of electron microscopy for diagnosis of NP-C and the marked clinical variability in patients with this disorder. Practical clinical guidelines for appropriate suspicion of NP-C are presented.

Clinical and Biochemical Manifestations of Hyaluronidase Deficiency

“…[11][12][13][14][15][16][17][18] Plasma and serum hyaluronidase activity was determined with human umbilical-cord hyaluronan (Sigma Chemical, St. Louis) (250 mg per liter) as the substrate. The results were similar for either type of specimen.…”

Niemann-Pick disease type C: Two cases and an update

“…Movement disorders, including dystonia, chorea, athetosis, and parkinsonism, can be part of the neurologic picture. 9,13,[16][17][18][19] Age of onset may determine the presence and frequency of certain clinical features. In a series of 20 pre-teenage cases with symptomatic narcolepsy with cataplexy, 12 patients had NPC.…”