Contributor: Gordon K. Klintworth
Mucopolysacharidosis type IIID (N-acetylglucosamine-6-sulfatase deficiency, Sanfilippo syndrome type D, OMIM #252940) is an autosomal recessive lysosomal storage disease caused by a mutation in the GNS gene, which results in deficiency of N-acetylglucosamine-6-sulfatase. A deficiency of this enzyme leads to an accumulation of partially degraded fragments of heparan sulfate in the tissues, the abnormal appearance of heparan sulfate in the urine and a slowly progressive atrophy of the cerebrum. Increased levels of gangliosides accumulate in the brain. The disease is usually diagnosed at 2-6 years of age and is ultimately fatal. The clinical manifestations include hyperactivity, attention deficit disorder, developmental delay, hirsutism, coarse facial features and hepatosplenomegaly. A progressive neurological deterioration with severe mental retardation begins in childhood and includes aphasia, vasomotor instability, epilepsy, and dementia. Some attributes of the syndrome resemble those of mucopolysaccharidosis type I-H and mucopolysaccharidosis type II (except with less dwarfism).