The report, “An Uncommon Presentation of Mucopolysaccharidosis Type IIIb,” was published in the Iranian Journal of Child Neurology.
MPS IIIB is a neurodegenerative lysosomal storage disorder caused by mutations in the NAGLU gene. This gene provides instructions for making the NAGLU enzyme, responsible for breaking down long complex sugar molecules called heparan sulfate (HS).
Mutations in the NAGLU gene reduce NAGLU activity, leading to the accumulation of heparan sulfate inside lysosomes — small, specialized cell compartments that digest and recycle different types of molecules — leading to metabolic impairments, inflammation and degeneration of the central nervous system.
Landau Kleffner syndrome (LKS) is a rare epilepsy syndrome that affects children between 3 and 10 years old, and is characterized by loss of language comprehension and speech. Children with LKS exhibit behavioral problems such as hyperactivity and attention deficits.
In this report, the authors present the case of a 9-year-old boy admitted to the Loghman Hospital in Tehran, Iran, with speech regression, seizures and ataxia (loss of muscle control).
He developed normally until 4 years of age when he started to show an attention deficit, inability to recognize objects/people (called agnosia), less ability to speak, and speech repetition.
At 6 years old, the boy began to have tonic-clonic seizures — those involving the entire brain — and locking his jaw while he slept. He also showed intermittent urinary incontinence. His symptoms progressed into autistic-like behaviors where he began repeating sounds or phrases (echolalia), had poor eye contact, and exhibited repetitive behavior.
Neurological analyses showed less blood flow in a brain area called the left centrotemporal lobe, and alterations in brain waves seen in an electroencephalogram (EEG), all consistent with an LKS diagnosis. Tests on the blood, kidneys, and liver showed no abnormalities.
Based on this diagnosis, clinicians prescribed commonly used medicines for LKS, including the steroid methylpredinisolone, valproate sodium, levetiracetam, and intravenous immunoglobulin as well as speech therapy. However, these treatments failed to ease his seizures, speech loss (aphasia), and behavior symptoms.
Due to his poor response to treatments and symptom progression, clinicians performed a genetic analysis for mutations that might explain why he was not improving. They found a mutation in the NAGLU gene consistent with a Sanfilippo type B diagnosis, which was considered the final diagnosis.
A urine analysis further revealed the presence of high levels of glycosaminoglycan, the large sugar molecules that accumulate in Sanfilippo patients.
“Given the heterogeneity of LKS, we propose considering other etiologies, such as metabolic disorders, in the patients diagnosed as having LKS,” researchers wrote. “This case showed that MPS III might be one of these metabolic disorders.”