Mild mental retardation and low levels of urinary heparan sulfate in a patient with the attenuated phenotype of mucopolysaccharidosis type IIIA

ObjectivesWe report the case of a 28-year-old female subject affected by the attenuated phenotype of mucopolysaccharidosis type IIIA characterized by moderate slowly evolving mental retardation in which the urinary content of heparan sulfate was demonstrated as being substantially low compared to that found in patients with the severe phenotype.Design and methodsThe specific evaluation of macromolecular heparan sulfate by electrophoresis and the determination of related glucosamine in the urine were performed.ResultsIn our patient, the urinary macromolecular heparan sulfate content (4.2 μg/mg creatinine) was ~ 7.5-times higher than in healthy subjects (0.56 μg/mg creatinine ± 0.9 SD) while it was ~ 28-times lower compared to the severe mucopolysaccharidosis IIIA group (117 μg/mg creatinine ± 44.8 SD). Furthermore, the urinary glucosamine (86.4 μg/mg creatinine) was ~ 2.4-times greater than in healthy subjects (36.0 μg/mg creatinine ± 18.2 SD) but ~ 2.4-times lower than in severe subjects (208.1 μg/mg creatinine ± 55.0 SD).ConclusionsThe above data could reflect the reduced heparan sulfate storage in her tissues and organs, and in particular in the brain, consequently explaining her moderate mental retardation. Furthermore, the clinical presentation of patients with an attenuated form of MPS III confirms the need for a specific evaluation of urinary GAGs in all young and adult subjects showing a not well-defined or not particularly severe mental retardation, along with an early MPS diagnosis. Such investigation should also be associated with a more specific characterization of heparan sulfate.