HUMAN MUCOPOLYSACCHARIDOSIS-IIID - CLINICAL, BIOCHEMICAL, MORPHOLOGICAL AND IMMUNOHISTOCHEMICAL CHARACTERISTICS

Mucopolysaccharidosis IIID (MPS HID) is one of the rarest of the MPS-I II syndromes. To date, the clinical manifestations of 10 patients have been reported, the deficient N-acetylglucosamine 6-sulfatase (G6S) en zyme has been purified, and the G6S gene has been cloned, sequenced an d localized. However, morphological manifestations of this condition h ave not been reported and the pathogenesis of the severe neurological deficits remains an enigma. In this paper we describe and correlate th e clinical, biochemical and pathological observations for 2 cases of M PS IIID. We used monoclonal antibodies against heparan sulfate (HS) an d G(M2)-ganglioside, thin layer chromatography, mass spectrometry, and morphological techniques to demonstrate the nature and the distributi on of the uncatabolized substrates. The majority of the cells in vario us tissues showed morphological changes expected with lysosomal storag e of HS. The central nervous system (CNS) was most severely affected b ecause of the secondary storage of G(M2) and G(M3) gangliosides in add ition to the primary accumulation of HS. The extent as well as the dis tribution of the diverse storage materials varied within and among dif ferent neurons as observed in MPS-III A. B, and C syndromes. This stud y supports the hypothesis that the neurological dysfunction and neurod egeneration common to the Sanfilippo syndromes is, in part, due to the secondary metabolic perturbations induced by HS accumulation.