NPC is an extremely rare and highly heterogeneous disease that affects multiple body systems and has variable onset and progression over a course of years. It is perhaps not surprising that in past decades it has frequently been misdiagnosed or even undetected at presentation in primary care. This was especially true before the characterisation of the primary molecular and genetic defects, when diagnosis relied on non-standardised histopathologic analysis, and has contributed to very varied terminology used to describe patients who are now known to have NPC: juvenile dystonic idiocy; juvenile dystonic lipidosis; neurovisceral lipidosis with vertical supranuclear gaze palsy, Neville–Lake disease, sea-blue histiocytosis, lactosylceramidosis; downgaze paralysis, ataxia and foam-cells syndrome (DAF).
Even now that direct biochemical and genetic tests are available, diagnosis can be challenging. This highlights the need for increased awareness of this disease, and for effective referral to specialist care for patients with suspected NPC. The following case history, adapted from the 2005 UK Department of Health report on the management of inherited metabolic diseases,1 highlights some of the problems associated with non-specialist centres advising parents without reference to up-to-date information on NPC.
Child 1 was a newborn baby girl who presented with severe neonatal jaundice and organomegaly. Initially it was thought that she had a severe infection and she was treated with antibiotics. However, there was no resolution and the liver disease persisted over the next few weeks, when it was thought that she had biliary atresia. Her parents were told that the liver disease was so severe she would die. A scan, followed by surgery, showed that this was not the case, and over the next 6 months she had a further four liver biopsies. Eventually, storage cells were found in the biopsies and a full metabolic work-up was performed, which eventually showed that she had NPC.
At this point, the parents were informed that Child 1 would not develop normally, would never walk or talk, and would die before the age of 2 years. By the time she was referred to the specialist team, the parents had already been referred to the local palliative care team. The fifirst task for the specialist nurse was therefore to ‘pick up the pieces’, as the parents were in extreme despair.
The nurse informed the parents that the natural history of the disease is very variable, and they were introduced in the clinic to parents of children up to the age of 5 years who had no neurological problems, so that they could see that the outlook may not be as bad as they had originally been told. They were also informed about possible genetic counselling and the options available to them if they wished to have more children.
When Child 1 was seen in clinic, at age 9 months, she was still very jaundiced. However, the last report on her at age 17 months was that she was developing well, had learned to walk and was speaking 18 recognisable words.1
References:
1. Burton H. Metabolic pathways Networks of Care: A needs assessment and review of services for people with inherited metabolic disease in the United Kingdom. Public Health Genetics Unit, 2005: available at www.phgfoundation.org/. Accessed 28th May 2009.
© 2007 Blackwell Publishing Limited. Reproduced by permission.