Accurate diagnosis of NPC requires awareness of many clinical phenotypes, narrowing of differential diagnosis by ancillary testing and final confirmation by biochemical testing – the current mainstay of primary diagnosis in NPC. In some cases, supportive information can be gained by assessments of histopathology and ultrastructural changes in skin or rectal biopsies. Molecular genetic testing is used generally to confirm the diagnosis in individuals with variant biochemical findings.1
Diagnostic procedures for NPC should be considered in individuals presenting with the features listed in Table 4.
| • Foetal ascites or neonatal liver disease, particularly when the latter is accompanied by prolonged jaundice and/or pulmonary infiltrates |
| • Infantile hypotonia without evidence of progression for months to years, followed by features outlined below: • Vertical supranuclear gaze palsy, progressive ataxia, dysarthria, dystonia, and in some cases, seizures and gelastic cataplexy • Onset of these symptoms in middle childhood, with progression |
| • Psychiatric presentations mimicking depression or schizophrenia, with few or subtle neurologic signs, starting during adolescence or adulthood |
| • Enlargement of the liver or spleen, particularly in early childhood |
References:
1. Patterson MC. Niemann–Pick disease Type C. Gene Reviews 2007a (updated 9 July). Accessible at: www.geneclinics.org. Accessed 28th May 2009.
© 2007 Blackwell Publishing Limited. Reproduced by permission.