TY - JOUR
T1 - Linear clinical progression, independent of age of onset, in Niemann-Pick disease, type C
AU - Yanjanin, Nicole M.
AU - Vélez, Jorge I.
AU - Gropman, Andrea
AU - King, Kelly
AU - Bianconi, Simona E.
AU - Conley, Sandra K.
AU - Brewer, Carmen C.
AU - Solomon, Beth
AU - Pavan, William J.
AU - Arcos-Burgos, Mauricio
AU - Patterson, Marc C.
AU - Porter, Forbes D.
PY - 2010/1
Y1 - 2010/1
N2 - Niemann-Pick disease, type C is a neurodegenerative, lysosomal storage disorder with a broad clinical spectrumand 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 symptomsin 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: Ŝt0+x= Ŝ t0 + 1.87x; where Ŝt0 is the initial score and Ŝt0+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 mayprove useful in the characterization of potential biomarkers, and as an outcome measure to monitor disease progression in NPC patients.
AB - Niemann-Pick disease, type C is a neurodegenerative, lysosomal storage disorder with a broad clinical spectrumand 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 symptomsin 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: Ŝt0+x= Ŝ t0 + 1.87x; where Ŝt0 is the initial score and Ŝt0+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 mayprove useful in the characterization of potential biomarkers, and as an outcome measure to monitor disease progression in NPC patients.
KW - Disease progression
KW - Lysosomal storage disease
KW - NPC1
KW - Neurodegenerative diseases
KW - Niemann-Pick disease
KW - Type C
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U2 - 10.1002/ajmg.b.30969
DO - 10.1002/ajmg.b.30969
M3 - Article
C2 - 19415691
AN - SCOPUS:73949159934
SN - 1552-4841
VL - 153
SP - 132
EP - 140
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 1
ER -