An accurate and early diagnosis of Sanfilippo syndrome type C can be difficult, as this subtype is quite rare, but important to prevent life-threatening complications and improve life quality, a case report highlighted.
The report, “A Rare case of Sanfilippo syndrome type ‘C’,” and published in the Indian Journal of Child Health, described a young girl who went years without a correct diagnosis for this progressive disorder, despite repeat examinations.
Sanfilippo type C, also known as mucopolysaccharidosis type IIIC (MPS IIIC), is a genetic lisosomal storage disorder caused by mutations in the HGSNAT gene, which provides instructions to make an enzyme called heparan-alpha-glucosaminide N-acetyltransferase.
In the absence of this enzyme, large sugar molecules called glycosaminoglycans (GAGs) start accumulating inside cells, leading to a series of neurological and cognitive impairments.
Among all sub-types of Sanfilippo syndrome, type C is one of the rarest, with an estimated prevalence of 1 case per 100,000 live births.
This high degree of variability in disease presentation and progression can make it hard for physicians to arrive at a definitive diagnosis.
Investigators described the case of a girl whose symptoms were first evident at age 4, but was not diagnosed with Sanfilippo syndrome type C until she was 8 years old.
The girl had mild intellectual disability, hyperactivity, and frequent insomnia by the time she arrived at their hospital’s pediatrics department. Signs of developmental delays began at age 4, her parents reported, and progressed by age 6 to sleep deprivation and hyperactivity.
“The patient’s parents consulted several primary care physicians, neurologists, psychiatrists, and pediatricians since appearance and progression of symptoms,” the investigators reported.
She underwent a battery of imaging, blood, and urine tests, but all results were within normal limits. Without a definitive diagnosis, she was started on symptomatic treatment, but failed to show any signs of improvement.
Lab tests performed at the hospital found abnormally high levels of heparan sulfate (71.3 mg/mM; normal range: 5.7–12.9 mg/mM), a type of GAG, in her urine. Such high levels are a clinical hallmark of Sanfilippo syndrome.
To confirm the diagnosis, physicians ordered a gene sequencing analysis, which revealed the girl had a missense mutation (c.1622>T) in both copies of the HGSNAT gene on exon 17. This mutation led to the substitution of the amino acid serine by that of leucine at position 541 of the protein sequence (p.Ser541Leu).
A missense mutation is a single nucleotide — the building blocks of DNA — mutation that alters protein composition by changing an amino acid sequence in the protein whose production the gene controls.
The girl began supportive care: cognitive behavioral therapy, speech therapy, and occupational therapy to address her intellectual disabilities and control her hyperactivity.
Her parents reported noticing improvements in her school performance, and lower hyperactivity levels.
“We are presenting this case because several diseases have similar clinical presentation and there is difficulty in making definitive diagnosis,” the researchers concluded.
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