Accumulation of heparan sulfate contributes to lysosomal dysfunction, autophagy impairment, disruption of mitochondrial functioning, and oxidative stress 3. Pathogenesis of neurological manifestations in MPS III involve both neuronal and non-neuronal cells in the central nervous system (CNS) 4. Accumulation of heparan sulfate accounts for predominant nervous system involvement in MPS type III, while in other MPS types impaired hydrolysis of chondroitin/dermatan sulfate leads to a more pronounced somatic presentation of the disease 3. Our patient was diagnosed with MPS IIIB (OMIM #252920), associated with a mutation in the NAGLU gene, which encodes α-N-acetylglucosaminidase on chromosome 17q21 1 c.1927C>T mutation is considered to cause an attenuated clinical phenotype of the disease 2. It consists of several subtypes depending on the site of the mutation and the following enzymatic deficiency in heparan sulfate catabolism. A metabolic lysosomal storage disorder, MPS III has an autosomal recessive inheritance. MPS type III (Sanfilippo syndrome) is the most common type of mucopolysaccharidoses (estimated prevalence 0.3-4.1 cases per 100,000 newborns). EEG monitoring also revealed interictal epileptiform activity in the frontal regions. The events were preceded by rhythmic fast activity over the frontal regions ( Figure 2). Overnight video-EEG monitoring was performed, which captured 21 focal stereotyped motor seizures, characterized by sudden startled awakenings and irregular hypermotor activity in all four limbs ( Figure 1). Based on these findings a diagnosis of mucopolysaccharidosis (MPS) type IIIB was made. Second heterozygous mutation was identified in exon 1 of the NAGLU gene (chr17:40688599G>A, c.309G>A, p.Trp103Ter). The first proband’s mutation was identified in exon 6 of the NAGLU gene (chr17:40695951C>T c.1927C>T, NM_0000263.3).

Both mutations were identified in the proband and confirmed by Sanger sequencing of the family trio (parentage verified). Two compound heterozygous mutations were revealed in the NAGLU gene through whole-exome sequencing (hg19). The level of urinary glycosaminoglicans was increased up to 14.3mg/ mmol (normal range 0-8.3mg/mmol). Brain MRI showed diffuse cerebral atrophy. Abdominal ultrasound exam revealed hepatomegaly. Neurological examination revealed signs of moderate dysarthria and coordination impairment. Upon admission, clinical examination revealed dolichocephaly, narrow forehead, thick eyebrows with synophris, hypertrichosis, prominent philtrum, broad nasal tip, and a thickened lower lip. At the time of admission, the patient was a college student, experiencing fatigue, attention decline, and affective lability that had a severe impact on her studies. Gait impairment and cognitive deterioration progressed over the course of the following years. Her mother first noticed poor coordination, disturbance of articulation and fine motor skills when the patient was three years old. These episodes first started at the age of 6, increasing from 5 to almost 60-70 per night by the age of 16. An 18-year-old female presented to our clinic with a history of disrupted sleep caused by sudden brief awakenings with hypermotor activity, lasting for 5-10 seconds, followed by muscle soreness.

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