Spectrum of phenotypic variability in Niemann-Pick type C disease: A cause of delayed diagnosis.

BACKGROUND

Niemann-Pick type C (NP-C) disease exhibits marked heterogeneity in its phenotype. This can pose diagnostic dilemmas and even delayed recognition of this condition.

OBJECTIVE

To highlight the phenotypic variations and distinctive pathological and biochemical findings in this disorder.

DESIGN

Descriptive case studies.

SETTING

Tertiary care children's hospital and clinic.

POPULATION STUDIED: Three cases of NP-C disease where diagnosis was delayed.

RESULTS

In each of the three cases the clinical presentation was varied, one as neonatal hepatitis, the second with megaloblastic anemia, chronic hepatitis and short stature, and the third with neonatal hepatitis and chronic respiratory failure. Definitive diagnosis was established in each case by demonstration of defective cholesterol esterification in skin fibroblasts.

CONCLUSIONS

In the clinical setting of neonatal hepatitis, hepatosplenomegaly and undiagnosed neurological symptoms, NP-C disease should be considered in the differential diagnosis. Electron microscopic examination of skin biopsy is an effective screening test, although the definitive diagnosis should be made by the cholesterol esterification assay and filipin staining.