New Sanfilippo type B mutation discovered in the Balkans
The Ser169-frameshift mutation in the NAGLU gene was new to researchers
A newly identified mutation was found in a boy from Kosovo with Sanfilippo syndrome type B alongside a well-known disease-causing mutation, a recent study reported.
Because this mutation had never been reported, the researchers said more research is needed to determine its frequency in the Balkan region of southern Europe.
The case study, “Mucopolysaccharidosis type III (subtype IIIB) diagnosis as a spectrum disorder: A case report from Kosovo,” was published in Folia Medica.
Sanfilippo syndrome, or mucopolysaccharidosis type III (MPS III), is a childhood disorder characterized by developmental delays, especially in speech, behavioral changes, sleep problems, loss of mobility, difficulty swallowing, and epilepsy. It’s caused by inherited deficiencies in one of four enzymes that break down heparan sulfate, a complex sugar molecule. Too much heparan sulfate in cells causes damage and inflammation, particularly in the brain.
Of the four types of Sanfilippo, those with type B carry mutations in the NAGLU gene, which leads to a deficiency in the enzyme alpha-N-acetylglucosaminidase (NAGLU). So far, more than 120 NAGLU mutations have been identified in type B patients.
Researchers in Kosovo described the case of a boy with Sanfilippo B due to a well-known NAGLU mutation that accounts for about 36% of cases, as well as a previously unreported mutation.
The boy was born into a family with no history of mental challenges or neurological disorders and appeared to develop normally.
At age 5, a physical examination showed altered facial features — prominent eyebrows, low-set ears, and a low hairline. Limb stiffness and an enlarged liver were also noted.
According to his parents, the boy was unable to control his urination and was constipated. He had motor development delays, such as an inability to walk, alongside cognitive impairment, hearing loss, epilepsy, and other signs specific to Sanfilippo syndrome.
MRI scans of his brain found periventricular leukomalacia, a type of brain injury to the white matter surrounding the brain’s fluid-filled ventricles that’s common in premature babies. White matter is mainly composed of nerve fibers, as opposed to gray matter that’s mostly made of nerve cell bodies. Evidence of white matter damage and brain shrinkage were detected.
Blood tests revealed low platelet counts and elevated liver enzymes, a sign of liver damage. His levels of alpha-N-acetylglucosamine, the molecule removed from heparan sulfate by the NAGLU enzyme, was five times lower than normal.
Genetic testing found two mutations in the NAGLU gene, confirming a Sanfilippo type B diagnosis.
One mutation — Y140C — has been described in numerous cases. The other, Ser169-frameshift (fs), had never been reported. Frameshift mutations are those involving the insertion or deletion of one letter in the DNA, which completely alters how the genetic code is read. This generally leads to an abnormal protein that doesn’t function properly.
Because his parents declined genetic analysis, the origin of the mutations — whether inherited or newly developed — couldn’t be determined. Researchers informed the parents about family support groups and indicated future pregnancies must be checked for NAGLU mutations.
“The yet unreported NAGLU gene mutation (Ser169fs) being identified here for the first time requires future studies to clarify if it is more frequent in [the] Balkan region,” the researchers concluded.