Childhood Alzheimer’s. The term has been in the news lately, as reports circulate of a young child from California who has dementia-like symptoms. The 2-year-old has trouble remembering words she already learned, for example. Her disease, properly known as Niemann Pick Type C (NPC), will cause increasingly severe cognitive decline. But is her condition related to Alzheimer’s disease? To learn more, WebMD spoke to Forbes Porter, MD, an NPC expert at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, a division of the NIH.
WebMD: Is there a connection between NPC and Alzheimer’s?
Porter: It’s a catchy term, but it’s not one that I or other people in the field like. Still, that doesn’t mean that there’s no overlap. Both diseases cause dementia. There is cognitive dementia in NPC, and that’s the main aspect that overlaps with Alzheimer’s. There’s something else they have in common as well. NPC results from a genetic mutation that causes cholesterol and other fatty substances to build up in various parts of the body, including the brain. Cholesterol metabolism also appears to play a role in Alzheimer’s. But, while it’s not totally separate, the connection is more catchy than informative. There are other neurodegenerative diseases with dementia in children, but NPC is the one that’s gotten tagged with the label ‘childhood Alzheimer’s.’
WebMD: How rare is NPC?
Porter: NPC affects an estimated one in 100,000 children. NPC1 is caused by a mutation of the NPC1 gene, which the child must inherit from both parents, who each carry the mutation but who don’t have the disease. Each child born to such parents has a 25% chance of developing NPC. While we know that mutations of the NPC1 gene cause the disease, we don’t know exactly how it controls movement of cholesterol in cells.
WebMD: What happens to children who get the disease?
Porter: There’s a very broad spectrum. If it starts to develop before birth or in infancy, it can cause severe, sometimes lethal, liver disease. The liver disease often tends to get better. Neurological manifestations often come later. In the classical disease, meaning when its onset begins in childhood or adolescence, there’s dementia in all patients, dementia and ataxia, or loss of muscle coordination which can affect speech, swallowing, and other functions. We are now learning that NPC also can occur in adults, who can present with psychiatric diseases like schizophrenia and bipolar disorder. Generally, these are young adults, but we have had much older patients as well.
WebMD: What are the symptoms of NPC?
Porter: Neurologically, the most common symptoms are problems with movement and muscle coordination caused by inflammation in the brain. These kids can initially be described as clumsy. Part of the difficulty with making the diagnosis is that many kids are clumsy. But as it progresses, kids with NPC start to lose skills that they have learned, such as the ability to walk independently. That’s really the hallmark of the degenerative disease, when you notice that the child is no longer able to do something that the child had been able to do. Cognitive decline is also pretty prominent. Usually that will manifest early on, often as the kid starts to struggle in school. Some patients have more trouble with motor functions and less trouble with cognitive problems; for others, it’s the reverse. But pretty much all of them have both.
WebMD: Do you know why there’s such variation in how and when the disease develops?
Porter: There’s a lot of work going into figuring out why it sometimes does not develop until adulthood. I’d love to know the reason. A lot of it is probably due to the individual mutation. Some mutations are more severe than others. In general, siblings with disease progress similarly, but there can be marked differences, too. That makes it clear that there are other genetic and/or environmental factors coming into play.
WebMD: How is NPC diagnosed?
Porter: Diagnosis is changing. In our research, we found that it took 4-to-5 years from the first time the parent reported a problem to receive a diagnosis. But that was using a much more difficult diagnostic test, and that likely contributed to the delay. We now have a blood test that can diagnose NPC, so I expect we will see that diagnostic delay decrease. Now, when doctors see children with cholestatic liver disease, the type of liver disease associated with NPC, they can send off a blood sample for DNA sequencing that can be used to identify numerous possible causes, including NPC.
WebMD: How do you treat NPC?
Porter: A drug called miglustat has shown some efficacy in slowing the neurological decline caused by NPC, but it’s definitely not where we want to be in treating this disease. While it is used in this country to treat Gaucher disease, the FDA has not approved it to treat NPC. Doctors, therefore, must prescribe it off-label, and insurance companies may deny coverage for the drug, which costs at least $ 10,000 a month. Another drug, called VTS-270, is currently being tested. A few months ago, we published a paper on a preliminary trial of VTS-270, and the data suggest that it can slow the neurological disease progression.
WebMD: Can NPC be cured?
Porter: No. Those who have it will die. Typically, they live with the disease for 10 to 15 years, and it gets progressively worse over that time. The younger the child when it develops, the more aggressive the disease can be. It’s a devastating disease. There’s a lot of work, a lot of effort ongoing to solve this. We don’t know if we’re going to get there, but there’s hope.