Linear clinical progression, independent of age of onset, in Niemann-Pick disease, type C

Nicole M. Yanjanin, Jorge I. Vélez, Andrea Gropman, Kelly King, Simona E. Bianconi, Sandra K. Conley, Carmen C. Brewer, Beth Solomon, William J. Pavan, Mauricio Arcos-Burgos, Marc C. Patterson, Forbes D. Porter

Research output: Contribution to journalArticlepeer-review

116 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)132-140
Number of pages9
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Issue number1
StatePublished - Jan 2010


  • Disease progression
  • Lysosomal storage disease
  • NPC1
  • Neurodegenerative diseases
  • Niemann-Pick disease
  • Type C

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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