They described the mutation in a case report titled, “A novel mutation in the NAGLU gene associated with Sanfilippo syndrome type B (mucopolysaccharidosis III B),” published in the journal Clinical Case Reports.
Sanfilippo syndrome type B, also known as mucopolysaccharidosis type III, is caused by mutations in the NAGLU gene, which instructs cells to produce an enzyme called alpha-N-acetylglucosaminidase. This enzyme is required for the degradation of large sugar molecules known as heparan sulfate glycosaminoglycans.
Patients with the disorder carry mutations in the NAGLU gene that reduce or eliminate the activity of the enzyme; as a consequence, excessive amounts of heparan sulfate accumulate inside cells, causing serious damage.
It is still unknown why the accumulation of heparan sulfate mostly affects the brain and spinal cord of the central nervous system, leading to the neurological deficiencies observed in Sanfilippo syndrome type B.
The report describes a new mutation in the NAGLU gene found in an infant suspected of having Sanfilippo syndrome type B.
The patient, a girl born in Sri Lanka, was the fourth child of consanguineous parents. Her first sibling was diagnosed with Sanfilippo syndrome type B and succumbed to the illness at 13. Her second sibling was delivered at 28 weeks of gestation and died soon after birth. Her third sibling is currently 4 years old and has no signs of the disease.
At 6 months, the girl began to show signs consistent with the disorder, including developmental delay, a decline of motor abilities, mild “coarse” facial features, and frequent respiratory infections.
Researchers screened the child’s DNA and identified a mutation that previously had never been reported on the NAGLU gene. The mutation changed one of the building blocks of the enzyme, an amino acid, for another.
Although at least 118 different NAGLU mutations have been found to cause Sanfilippo syndrome type B, this new mutation is associated with unique features and was missing from population genetic databases and clinical databases.
Researchers hypothesized that this particular mutation leads to perturbations in the NAGLU enzyme’s structure and function, hence resulting in Sanfilippo syndrome type B.