Sanfilippo syndrome and its kind: when sugars don’t go away
May 18, 2012 § 2 Comments
My awesome editor, Angela Hopp, heard this heart-wrenching story on our local public radio station the other day and told me about it. The story is about a father, Matt McNeil, trying to make sense of life as he and his wife take care of their two children who are stricken with Sanfilippo syndrome. His 8-year-old daughter, Waverly, and 5-year-old son, Oliver, both have the abilities of a 1-year-old. They can’t talk. The little girl is in a wheelchair because she can’t walk. Unless a cure is found, both of them eventually won’t be able chew and swallow.
I admit I had never heard of the syndrome so I was curious. In reporting the story, Rebecca Sheir quickly explained it was a rare genetic disease in which the enzyme needed to break down natural sugars in the body was missing. But what enzyme was it, and what was its normal functions?
One of the huge perks of working at ASBMB is having the world’s experts in molecular biology and biochemistry at my fingertips. Within minutes of shooting out an email, I had a well-known glycobiologist, Jerry Hart at Johns Hopkins University, pointing me to all kinds of resources to explain what the disease was all about.
Sanfilippo syndrome belongs to a class of diseases known as mucopolysaccharidosis, or MPS. Sanfilippo syndrome, named after pediatrician Sylvester Sanfilippo who first described it, is known as MPS III. It’s thought that Sanfilippo syndrome is the most common forms of MPS; it has an occurrence of about 1 in 70,000 births.
The syndrome is caused by an inability to break down heparan sulfate, a linear polysaccharide. There are four versions of Sanfilippo syndrome, depending on which one of the four enzymes that break down heparan sulfate is missing. Children with Sanfilippo syndrome have mutations in heparan N-sulfatase, alpha-N-acetylglucosaminidase, acetyl-CoA glucosaminide acetyltransferase or N-acetylglucosamine 6-sulfatase.
When one of these enzymes is missing or defective, the breakdown of heparan sulfate grinds to a halt. Partially chewed up fragments of heparan sulfate accumulate inside the lysosomes, the organelles that digest and recycle molecules. The buildup of heparan sulfate fragments interferes with the digestion and recycling of other molecules. For this reason, Sanfilippo syndrome is considered to be a lysosomal storage disorder. But no one knows yet why an accumulation of heparan sulfate in Sanfilippo syndrome patients primarily attacks the central nervous system.
The story of Waverly and Oliver’s lives with Sanfilippo syndrome drives home a point Hart wants to make when he gives talks. He shared with me the PowerPoint slides he recently used to talk about congenital diseases involving glycosylation. In one of them, he has the statement, “Glycans are no less important to human health than proteins or DNA!”