Abstract:
BACKGROUND : Niemann-Pick disease Type C (NP-C) is a genetic lipid storage disorder characterised by progressive
neurovisceral symptomatology. Typically, disease progression ismore pronounced in patientswith early onset of
neurological symptoms. Heterogeneous clinical presentation may hinder disease recognition and lead to delays
in diagnosis. Here we describe the prevalence of signs and symptoms observed in patientswith NP-C and analyse
the relationship between these symptoms in different age groups.
METHODS : The combined patient cohort used in the analyses comprised NP-C cases (n=164) and controls (n=
135) aged 0 to 60 years from two previously published cohorts; a cohort of all ages fromwhich patients ≤4 years
of agewere excluded and a cohortwith early-onset NP-C and age-matched controls. The analysis of relationships
between different signs and symptoms was performed for both NP-C cases and controls in two sub-groups, ≤4
and N4 years of age, using cluster analyses. The threshold of 4 years of age was selected to reflect the minimum
age cut-off for satisfactory discriminatory power of the original NP-C SI. To assess the prevalence of individual
signs and symptoms at age of diagnosis, patientswere categorised by age into 5-year sub-groups, and prevalence
values estimated for each sign and symptom of NP-C.
RESULTS : Twomain clusters of symptomswere clearly defined for NP-C cases in each age sub-group,whereas clusters
were not as clearly defined for controls. For NP-C cases ≤4 years of age, one cluster comprised exclusively
visceral symptoms; the second cluster combined all other signs and symptoms in this age group. For NP-C
cases N4 years of age, each cluster contained amixture of visceral, neurological and psychiatric items. Prevalence
estimations showed that visceral symptoms (e.g. isolated unexplained splenomegaly)were most common inNPC
cases ≤4 years of age. Neurological symptoms were generallymore common in NP-C cases N4 years of age than
in younger patients, with the exception of hypotonia and delayed developmental milestones.
CONCLUSIONS : These analyses provide a comprehensive overviewof symptomatology observed in a large combined
cohort of patients with NP-C and controls across a wide range of ages. The results largely reflect observations
from clinical practice and support the importance of multi-disciplinary approaches for identification of patients
with NP-C, taking into account age-specific manifestations and their possible correlations.
