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

We 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 sulphate was demonstrated as being substantially low compared to that found in patients with the severe phenotype. The specific evaluation of macromolecular heparan sulfate by electrophoresis and the determination of related glucosamine in the urine were performed. In our patient, the urinary macromolecular heparan sulfate content (4.2 mcg/mg creatinine) was about 7.5-times higher than in healthy subjects (0.56 mcg/mg creatinine+/- 0.9 SD) while it was about 28-times lower compared to the severe mucopolysaccharidosis IIIA group (117 mcg/mg creatinine +/- 44.8 SD). Furthermore, the urinary glucosamine (86.4 mcg/mg creatinine) was about 2.4 times greater than in healthy subjects (36.0 mcg/mg creatinine +/-18.2 SD) but about 2.4 times lower than in severe subjects (208.1 mcg/mg creatinine +/- 55 SD). The above data could reflect the reduced hepara sulfate storage in her tissues and organs, and in particular in the brain, consequently explaing her moderate mental retardation. Furthermore, the clinical presentation of patients with 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 particulary severe mental retardation along with an early MPS diagnosis. Such investigation should also be associated with a more specific characterization of heparan sulfate.