Sanfilippo Type B Patient May Be First in Saudi Arabia
8-year-old has a novel mutation in the NAGLU gene
A never-before-reported mutation in the gene NAGLU was found to cause Sanfilippo syndrome type B in an 8-year-old girl in Saudi Arabia.
“To the best of our knowledge, this is the first report of Sanfilippo syndrome type B from Saudi Arabia,” researchers said.
The case was described in the report, “A Novel Mutation in the NAGLU (N-Acetyl-Alpha-Glucosaminidase) Gene Associated With Mucopolysaccharidosis Type III-B in a Saudi Girl,” published in Cureus.
Sanfilippo syndrome is caused by mutations that impair the body’s ability to break down the sugar molecule heparan sulfate, leading this molecule to build up to toxic levels inside of cells. Mutations in the NAGLU gene specifically cause type B disease.
The report describes the case of a child born to consanguineous (biologically related) patients in Saudi Arabia. The girl had been born with an unusually low birth weight and a delayed first cry, and required intensive care in the first months of life.
The girl’s parents reported she had experienced marked delays in development — for example, she did not begin to walk until around age 4 — and that she had experienced notable cognitive decline over the course of her childhood.
She had a number of co-occurring health issues, including cataracts, hearing loss, problems with heart health, and scoliosis (sideways curvature of the spine). The researchers describe the girl as having “coarse facial features, thick eyebrows, deep-seated eyes, thinning coarse hair, and macrocephaly,” which is an enlarged head compared to body size. She also had substantial muscle atrophy, and laboratory tests were indicative of malnutrition and muscle wasting.
The girl had never been to school, and due to immobility and trouble swallowing, she needed daily assistance.
The girl was diagnosed with Sanfilippo syndrome when she was 4 years old. The diagnosis was confirmed by genetic testing, which identified a novel mutation in the NAGLU gene, designated c.889C>T, p.(Arg297*).
Of note, analyses of the patient’s urine at the time of diagnosis did not show any abnormalities in levels of glycosaminoglycans (GAGs) — a group of sugars that includes heparan sulfate.
“This suggests that a negative urinary GAG test does not rule out the diagnosis [of Sanfilippo syndrome], especially when the test is ordered at a young age,” the researchers wrote.
“Besides the clinical presentation, hospitals should utilize different investigation modalities such as laboratory data, genetic testing, and imaging findings to reach a proper diagnosis in a timely manner,” they added.