Linear clinical progression, independent of age of onset, in Niemann-Pick disease, type C.
Niemann-Pick disease, type C is a neurodegenerative, lysosomal storage disorder with a broad clinical spectrum and a variable age of onset. The absence of a universally accepted clinical outcome measure is an impediment to the design of a therapeutic trial for NPC. Thus, we developed a clinical severity scale to characterize and quantify disease progression. Clinical signs and symptoms in nine major (ambulation, cognition, eye movement, fine motor, hearing, memory, seizures, speech, and swallowing) and eight minor (auditory brainstem response, behavior, gelastic cataplexy, hyperreflexia, incontinence, narcolepsy, psychiatric, and respiratory problems) domains were scored. Data were collected from 18 current NPC patients and were extracted from records of 19 patients. Both patient cohorts showed a linear increase in severity scores over time. Cross-sectional evaluation of current patients showed a linear increase in the severity score. Longitudinal chart review of historical data demonstrated that although age of onset varied significantly, the rate of progression appeared linear, independent of age of onset, and similar in all patients. Combining the data from both cohorts, disease progression could be modeled by the following equation: ŝ(t0+x) = ŝ(t0) + 1.87x; where ŝ(t0) is the initial score and ŝ(t0+x) is the predicted future score after x years. Our observation that disease progression is similar across patients and independent of age of onset is consistent with a biphasic pathological model for NPC. This scale may prove useful in the characterization of potential biomarkers, and as an outcome measure to monitor disease progression in NPC patients.
Program on Developmental Endocrinology and Genetics, NICHD, NIH, DHHS, Bethesda, Maryland, USA.
Nicole M
NM
Yanjanin
Jorge I
JI
Vélez
Andrea
A
Gropman
Kelly
K
King
Simona E
SE
Bianconi
Sandra K
SK
Conley
Carmen C
CC
Brewer
Beth
B
Solomon
William J
WJ
Pavan
Mauricio
M
Arcos-Burgos
Marc C
MC
Patterson
Forbes D
FD
Porter
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D052556:Niemann-Pick Disease, Type C / Q000473:pathology*; D012720:Severity of Illness Index; D055815:Young Adult