Mucopolysaccharidosis IIIB (Sanfilippo syndrome type B) masquerading as a behavioral disorder

Abstract

Lysosomal storage diseases (LSD) are a heterogeneous group of approximately 60 disorders caused by lysosomal dysfunction. The significant variability in the age of onset, rate of progression, and symptomatology of these disorders can make diagnosis difficult, particularly for those LSD with later onset and delayed progression. We report a 25-year-old female who exhibited profound behavioral issues andmild learning disabilities in childhood. As a result, shewas diagnosed with multiple psychiatric disorders, and treated to attain acceptable behavior. In her mid-twenties, she manifested a rapid cognitive decline. Brain imaging studies showed moderate cortical atrophy and significant deposition of metal in several regions. Her family history was notable for an older sister with a very similar phenotype. In the absence of signs pathognomonic for their disease, we pursued whole exome sequencing of the family. This identified compound heterozygous mutations in NAGLU,which encodesN-acetyl-D-glucosaminidase. Biochemical studies confirmed enzyme deficiency diagnostic of mucopolysaccharidosis IIIB (Sanfilippo syndrome). Both the initial behavioral presentation and late onset of cognitive decline contributed to the 22-year diagnostic odyssey of this patient. This case demonstrates the importance of considering late-onset metabolic disorders, such as Sanfilippo syndrome, when evaluating individuals in a mental-health setting who exhibit behavioral abnormalities and learning disabilities.