Early Diagnosis Vital for Counseling At-risk Sanfilippo Type B Families, Study Shows

Long-term clinical course examination is important for diagnosing Sanfilippo syndrome type B, because early and accurate diagnosis can provide important information for family planning by those at risk of the disorder.

The story with that finding, “Long-term clinical course of a patient with mucopolysaccharidosis type IIIB,” was published in the Korean Journal of Paediatrics.

Depending on the enzyme affected, mucopolysaccharidosis type III (MPS III; Sanfilippo syndrome) can be divided into four known subtypes: A, B, C and D.

Because patients with certain MPS subtypes, like MPS IIIB, do not display many obvious physical changes, the disease often is under-diagnosed and enzyme activity tests are necessary to distinguish among these four subtypes.

This disease also rare is (estimated incidence of 0.3-1.9 in every 100,000 live births);  as such, there is a dearth of long-course studies.

This report presents the case of a Korean MPS IIIB patient whose condition was followed for 20 years.

The boy was born at full-term to healthy non-consanguineous parents. He showed normal development until age three. When he was referred to a genetic centre at age four, he did not show any abnormalities relating to hearing or sight. There were, however, some bone development abnormalities.

An enzyme activity test for MPS gave a positive result. At the time, the patient was treated with enzyme-replacement therapy (ERT) for MPS I and was discharged without follow-up.

At age 13, the patient revisited the same center with pneumonia and motor abnormalities. He had behavioral abnormalities such as aggressiveness, anxiety and sleep disturbances throughout his childhood. Communication function also had been lost.

Facial dysmorphism, including coarse facial features, a depressed nasal bridge, prominent eyebrows, and malocclusion (misalignment of the teeth when the jaws are closed), was apparent at ages 13 and 18.  Epilepsy developed at 18 years of age.

The patient was bedridden and malnourished at age 21, at which time he showed severe cognitive dysfunction.

Overall this evidence suggested a case of MPS III. Genetic tests indicated he had a deficiency in the enzyme alpha-N-acetyl-D-glucosaminidase (NAGLU), and the patient was diagnosed with MPS IIIB.

“MPS III has a unique clinical course. Early development is typically normal or near normal, but developmental regression or behavioral problem present between the ages of 2 to 6 years,” the authors wrote. “Therefore, patients in early childhood have been misdiagnosed with idiopathic developmental delay, attention deficit/hyperactivity disorder, or autism spectrum disorders,” they added.

As such, researchers believe an “early and accurate diagnosis of MPS is imperative to optimize clinical outcomes, particularly for those disorders that are ameliorated by ERT or hematopoietic stem cell transplantation.”

“Although there are no effective therapies yet in MPS III, early diagnosis is crucial for genetic counseling in at-risk families,” they concluded.