This (MPS VII) is a rare type of mucopolysaccharidosis, the clinical features of which have yet to be sharply delineated. Short stature, progressive thoracolumbar gibbus, hepatosplenomegaly, and the bony changes of dysostosis multiplex (as in the Hurler type) are the main clinical features. There is excessive excretion of dermatan and heparan sulfate, the result of a deficiency of b-glucuronidase. Attempts to treat the mucopolysaccharidoses by enzyme replacement therapy, bone marrow transplantation, and gene transfer are in progress. The enzyme replacement, vestronidase, is in use.
Mucolipidoses and Other Diseases of Complex Carbohydrates (Sialidoses; Oligosaccharidoses) (See Table 36-3)
Several diseases have been described in which there is an abnormal accumulation of mucopolysaccharides, sphingolipids, and glycolipids in visceral, mesenchymal, and neural tissues, because of an a-N-acetylneuraminidase defect. In some types there is an additional deficiency of beta-galactosidase. All are autosomal recessive diseases that manifest many of the clinical features of Hurler disease, but—in contrast to the mucopolysaccharidoses—normal amounts of mucopolysaccharides are excreted in the urine. Frequently, GM1 gangliosidosis, described above, is also classified with the mucolipidoses. The other members of this category are synopsized below and in Table 36-3. There is yet no specific treatment for these disorders.
At least three and possibly four closely related forms have been described. In mucolipidosis I (lipomucopolysaccharidosis), the morphologic features are those of gargoylism, with slowly progressive developmental impairment. Cherry-red spots in the maculae, corneal opacities, and ataxia have been noted in some patients. Vacuolation of lymphocytes, marrow cells, hepatocytes, and Kupffer cells in the liver and metachromatic changes in the sural nerve have been described.
In mucolipidosis II (I-cell disease), the most common of the mucolipidoses, there is usually an early onset of psychomotor delay, but in some cases this does not appear until the second or third decade of life. Abnormal facies and periosteal thickening (dysostosis multiplex, like that of GM1 gangliosidosis and Hurler disease) are characteristic. Gingival hyperplasia is prominent, and the liver and spleen are enlarged; but deafness is not found and corneal opacities are slower to develop. Tonic-clonic seizures are frequent in older patients. In most cases, death from heart failure occurs by the third to eighth year. There is a typical vacuolation of lymphocytes, Kupffer cells, and cells of the renal glomeruli. Bone marrow cells are also vacuolated and contain refractile cytoplasmic granules (hence the designation inclusion-cell, or I-cell, disease). A deficiency of several lysosomal enzymes required for the catabolism of mucopolysaccharides, glycolipids, and glycoproteins have been found.
In mucolipidosis III (pseudo-Hurler polydystrophy), the biochemical abnormalities are like those of I-cell disease, but there are clinical differences. In the pseudo-Hurler type, symptoms do not appear until 2 years of age or later and are relatively mild. Retardation of growth, fine corneal opacities, and valvular heart disease are the major manifestations.