Abstract
Objectives
To describe the clinical evolution of Niemann–Pick C disease to identify possible
factors involved in the diagnosis and severity of the disease.
Methods
A clinical database and a severity scale was created to evaluate 45 patients diagnosed
with Niemann–Pick type C in the last 28 years in Spain.
Results
Complete clinical data were obtained from 30 patients, all were confirmed to have
mutations in the NPC1 gene. Regarding clinical form, 3 were perinatal, 7 severe infantile, 6 late infantile,
11 juvenile and 3 adult. Biochemical phenotype was classic in 26. Splenomegaly was
present in 28 patients (93%) with a wide range of age at detection. The first symptom
of neurological disease was clumsiness, followed in 2–4 years by cerebellar signs.
Ophthalmoplegia appeared 2–4 years later and became complete 1–2 years after onset.
Dysarthria appeared by the time of complete ophthalmoplegia. Diagnosis was made before
the onset of neurological signs in patients with the severe infantile form, at the
time of onset of cerebellar signs in the late infantile form and complete ophthalmoplegia
in late onset forms.
Conclusions
In our series, splenomegaly is present in 96% of patients, even in late onset forms
during the first years of life. Clumsiness in children with otherwise normal motor
development precedes the onset of ataxia by 2–4 years in Niemann Pick type C. A disability
scale could be useful for monitoring evolution, establishing possible phenotypic correlations
and evaluating future therapies.
Abbreviations:
NPC (Niemann–Pick disease type C), SI (severe infantile form), LI (late infantile form)Keywords
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Article info
Publication history
Accepted:
May 10,
2006
Received in revised form:
May 9,
2006
Received:
January 27,
2006
Identification
Copyright
© 2006 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
