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Niemann-Pick disease type C: diagnosis and outcome in children, with particular reference to liver disease
D A Kelly1, B Portmann, A P Mowat
1Liver Unit, Children's Hospital, Birmingham, United Kingdom.
Insights
Niemann-Pick disease type C diagnosis is key for infants with neonatal hepatitis and persistent splenomegaly. Bone marrow aspiration is recommended due to potential normal liver biopsy results.
Area of Science:
- Pediatric Hepatology
- Neurology
- Rare Genetic Disorders
Background:
- Niemann-Pick disease type C (NPC) is a rare lysosomal storage disorder.
- Clinical presentation and outcomes in NPC can vary significantly.
- Early diagnosis and understanding disease progression are crucial for patient management.
Purpose of the Study:
- To determine if Niemann-Pick disease type C progression and outcomes differ based on initial clinical presentation.
- To analyze the long-term effects of early cholestatic liver disease in NPC.
- To correlate clinical patterns with disease severity and survival.
Main Methods:
- Retrospective review of medical records for 52 children diagnosed with Niemann-Pick disease type C.
- Analysis of initial clinical patterns, including cholestatic liver disease, hepatosplenomegaly, and neurologic symptoms.
- Evaluation of disease progression, liver function tests, liver biopsy findings, and survival rates.
Main Results:
- Of 52 children, 34 presented with neonatal cholestatic liver disease and hepatosplenomegaly; 18 presented later with splenomegaly or neurologic disease.
- Early liver disease resolved in most, but persistent splenomegaly was common.
- Neurologic disease onset and pattern were similar regardless of early liver involvement; bronchopneumonia was the main cause of death.
Conclusions:
- Niemann-Pick disease type C should be suspected in infants with unexplained neonatal hepatitis and persistent splenomegaly.
- Liver biopsy may not always show storage cells; bone marrow aspiration is recommended for diagnosis.
- Despite variable initial presentation, neurologic disease significantly impacts outcomes in Niemann-Pick disease type C.
Abstract:
The records of 52 children with Niemann-Pick disease type C were reviewed to establish whether the disease process and outcome varied with the initial clinical pattern; 34 children (65%) had cholestatic liver disease and hepatosplenomegaly in infancy; 18 were seen at a mean age of 4 years with splenomegaly or neurologic disease or both. Of the 34 children with early cholestatic liver disease, three died in the neonatal period; cholestasis and hepatomegaly subsided in the remaining 31 children, although splenomegaly persisted. Of these 31 children, 15 had persistent liver disease with elevated aminotransferase values. Serial liver biopsy specimens showed that 3 of the 15 children had normal architecture and 12 had hepatic fibrosis, with progression to cirrhosis in 5. No other significant morbidity or additional deaths were associated with the liver disease. The clinical importance of persistent liver disease was overshadowed by the subsequent development of severe neurologic disease. There was no difference in the age at onset of the disease (mean, 4.5 years) or in the pattern of neurologic disease, including supranuclear ophthalmoplegia, whether or not the child had early liver disease. Overt neurologic disease has not yet developed in seven surviving children with liver disease at onset. Sixty-seven percent of children died during the study; the main cause of death was bronchopneumonia. We conclude that the diagnosis of Niemann-Pick disease type C should be considered in patients with unexplained neonatal hepatitis, especially if splenomegaly is a persistent feature. Because liver biopsy specimens may not demonstrate storage cells, bone marrow aspiration to detect the characteristic storage cells is recommended in such patients.