11 Things Doctors Need You to Know About Childhood Alzheimer’s

The name “childhood Alzheimer’s” isn’t technically correct

Childhood Alzheimer’s has been used colloquially to refer to children who show dementia-like symptoms, but the cause is very different than Alzheimer’s as seen in adults. A couple of diseases that fall under a family of more than 50 conditions known as “lysosomal storage disorders”—namely, Niemann-Pick disease type C (NPC) and Sanfilippo syndrome (mucopolysaccharidosis type III, also referred to as MPS III)—can cause such symptoms in children (and are extremely rare). Both NPC and MPS III are scientifically different from Alzheimer’s, explains Steven Walkley, DVM, PhD, professor of neuroscience and director of the Rose F. Kennedy Intellectual and Developmental Disabilities Research Center at Albert Einstein College of Medicine in Bronx, New York.

Alzheimer’s disease is a neurodegenerative condition seen in adults. It refers to abnormal levels of a naturally occurring protein (beta-amyloid) in the brain, which clump together between cells to form plaques that can interfere with brain connections. “These changes are associated with the onset and progression of dementia,” says Dr. Walkley.

So what happens in childhood Alzheimer’s?

The diseases responsible for this tragic condition—NPC and MPS-III—are genetic, neurodevelopmental, and neurodegenerative diseases. Both involve the breakdown of a crucial digestive structure in cells called the lysosome: This unit helps cells process cholesterol and sugar and push them out of cells so the body can put them to use. When there’s a missing or abnormal protein in the lysosome, these important nutrients pile up inside cells, depriving the body of important nutrients and causing cells to behave erratically and eventually die off.

What Alzheimer’s, NPC, and MPS III, do have in common is the deterioration of the brain cells is progressive over time, leading to dementia—but the underlying cause is different and, for patients of the childhood Alzheimer’s diseases, the brain is just one of many organs and systems in the body that suffer damage.

Childhood Alzheimer’s isn’t limited to young children

The progression of childhood Alzheimer’s-like diseases NPC and MPS III can vary widely. A person might suffer a very mild or slow-progressing form of the disease, and live into their twenties, explains Dr. Walkley. Signs of NPC (such as a large liver) can be detected in infancy, and even before birth. Very generally speaking, though, parents or doctors will notice the symptoms of NPC by the time a child turns six. When it comes to MPS III, parents may not notice symptoms until their child begins to walk. In a typical case of MPS III, that can happen in preschool or kindergarten. Parents often don’t realize their child has an issue until he’s in school and not keeping up with the other kids. He might get special help—at which point a teacher or aide may notice that the child’s knowledge base is declining, explains Chester Whitley, PhD, MD, professor of pediatrics at the University of Minnesota Medical School in Minneapolis. Typically, an infected child won’t survive past their teenage years.

It damages more than memory

The brain symptoms may be the first thing parents notice, but the diseases can also attack other structures and organs: A child will lose dexterity, balance, and the ability to speak. A child with NPC will have a hard time moving their eyes to look up or down; they might blink a lot or jerk their neck; they’ll also experience seizures and motor problems. In the case of MPS III children (who tend to have distinctive facial features, such as a large forehead and coarse hair), they might seem hyperactive and have terrible insomnia, explains Patricia Dickson, MD, chair of the scientific advisory board at the National MPS Society.

It’s rare and genetic

Experts are unsure of the number of children at risk since the diseases are often missed—or misdiagnosed. Some reports suggest that NPC occurs in 1 out of 100,000 to 150,000 live births; MPS III may turn up in 1 out of 70,000 to 100,000 births. Because the diseases depend on recessive genes, each parent must be a carrier—this means their offspring will have a one in four chance of developing the condition.

How do genes play a role?

Parents pass on mutated genes that produce deformed versions of the NPC-1 or NPC-2 protein (or the genes they may not produce the protein at all). These proteins are responsible for moving cholesterol and other lipids out of the lysosome in a cell—which has a huge impact on a person’s overall health. “Cholesterol is needed to make cell membranes, steroids, and vitamins,” says NPC researcher Charles Vite, PhD, DVM, a professor of neurology and neurosurgery in the department of clinical studies at the University of Pennsylvania’s School of Veterinary Medicine. “If the cholesterol can’t get out of the lysosome, then it can’t help perform these functions.” In addition, cholesterol and other lipids accumulate in the cell, which causes it to function abnormally and sometimes to die.

MPS III patients have a defect in one of four genes (denoted by MPS III A, B, C, or D), each of which is responsible for an enzyme that breaks down a particular type of sugar molecule. As the sugar builds up, brain and organ function declines; gradually the cell dies, explains Dr. Dickson.

Pediatricians often think the disease is something else

Because the condition is rare, pediatricians don’t look for it; also, the symptoms can be subtle and easy to miss. A parent may feel that something is “off,” but a doctor unfamiliar with the condition may reassure the parents that the child is just experiencing a developmental delay, a learning disability, or some other neurological condition—MPS III can resemble autism, for example. While genetic tests like whole exome sequencing can lead to a diagnosis, it’s not uncommon that parents and their child will undergo what’s considered a “diagnostic odyssey.” Here are nine ways to find a pediatrician you can trust.

It can take years to get an answer

“The average time it takes a patient to get the right diagnosis [for NPC] is about six years,” says Elizabeth Berry-Kravis, MD, PhD, professor of pediatrics, neurological sciences, and biochemistry at Rush University Medical Center in Chicago. Patients and their families almost never hear the diagnosis from their own pediatrician. Finding an answer typically involves seeing specialists and geneticists. You could try ordering up your own genetic test, though here’s what your doctor probably isn’t telling you about 23andMe and other genetic tests.

The same is true for MPS III, according to Dr. Whitley, who is also head of the Lysosomal Disease Network. He’s currently involved with launching a project on diagnostic odysseys: the goal is to figure out how long diagnosis takes, on average, and define the financial and emotional costs associated with the delay. Dr. Whitley is also hoping to rally support for the inclusion of lysosomal diseases in newborn screenings. While each of the diseases behind childhood Alzheimer’s is rare, put together they occur in 1 in 5,000 live births—that’s as common as some of the conditions doctors already routinely screen for in newborns.

It has gotten easier to confirm the diseases

As recently as a few years ago, doctors needed to do a skin biopsy and a culture of skin cells to confirm NPC, explains Dr. Whitley. For MPS III, urine tests provided a quick screen, followed by a blood test to zero in on what particular form of MPS the child might have. Now, both diseases can be directly diagnosed with a high degree of accuracy using just blood tests, says Dr. Dickson.

There is no cure, but, for some patients, treatments are on the horizon

Unfortunately, no pill or surgery can reverse symptoms. “It’s extremely hard to treat genetic brain diseases,” says Dr. Walkley. “It’s hard to know which metabolic pathways to alter to prevent a disease that’s ongoing in the brain.” In the case of patients with an NPC-1 mutation, cyclodextrin (incidentally, the active ingredient in Febreze air fresheners) appears extremely promising as a way to control the disease. “It’s not the perfect treatment, but it’s a major step forward,” says Dr. Walkley. Injected into the spine, the drug seems to halt the disease’s progression and stabilize the condition. He believes the treatment could be available soon.

A couple of treatments for MPS III show promise, but they’re still years away from FDA approval. Among the two furthest along, says Dr. Dickson, is a form of gene therapy and a form of enzyme therapy.

Support is out there

If your child has NPC or MPS III, you can find lots of helpful information and advice through support groups. Organizations composed of doctors, researchers, and families with children suffering from the condition can assist families in getting the help they need. If your child has MPS, get in touch with groups such as the National MPS Society, the Cure Sanfilippo Foundation, and Jonah’s Just Begun. If your child has NPC, check out the National Niemann-Pick Disease Foundation, the Ara Parseghian Medical Research Foundation, and Support of Accelerated Research for NPC. As is the case with any other incurable disease, you’ll want to visit clinicaltrials.gov to register for any studies that may prove helpful for your child. No treatment can reverse the damage already done, which is why Dr. Whitley stresses that “it’s important to get help as early as you can.” By reaching out, you’ll also realize that you’re not alone.