Mucolipidosis II . I-cell disease. N-acetylglucosaminyl-1-phosphotransferasa deficiency.
Incidence
Autosomal recessive disorder. Both sexes are affected. Is probably the most frequent of the mucolipidosis. In French Canadian population the incidence is one in six thousand.
Clinical Characteristics
This condition is a Hurler-like condition with severe clinical and radiological features, peculiar fibroblast inclusions, and no excessive mucopolysacchariduria. Congenital dislocation of the hip, thoracic deformities, hernias and hyperplastic gums are evident soon after birth. Retarded psychomotor development, clear corneas and restricted joint mobility are other features. The condition is related to defect of N-acetylglucosaminyl-1-phosphotransferasa. The clinical and radiological features of this autosomal recessive disorder is reminiscent of Hurler syndrome but the symptoms are present since birth. Features seen in the affected newborn include hypotonia, coarse facial appearance, striking gingival hyperplasia, congenital dislocation of hips, restricted joint mobility and tight thicken skin. Radiographic changes of dysostosis multiplex develop between ages of six and ten months. Subsequently, growth failure and progressive mental deterioration become apparent. Hepatomegaly and corneal clouding are inconstant. Most patients die during childhood. Non-immune hydrops fetalis can be seen in some pregnancies. Cultured fibroblasts contain numerous inclusions. These inclusions represent large lysosomes filled with mucopolysaccharides and membranous material. Several lysosomal hydrolases are markedly elevated in serum but deficient in fibroblasts. The enzymes levels in liver and brain are normal. Neonates tends to be small for date. Motor retardation is evident early and by the second year mental retardation is obvious. Speech is never obtained. Most children never walk. The gums are hyperplastic since birth and within the first few months of life, abnormal facial features, limitation of joint movements, thick skin, hirsutism and radiological changes of the long bones begin to appear. In the bones, there are changes similar to infantile osteomalacia or rickets with generalized demineralization, periosteal new bone formation, coarse trabeculation and broad irregular metaphyseal lines. These changes are similar to those seen in mucopolysaccharidosis and other lysosomal diseases. In the second to third year, facial dysmorphism and skeletal dysplasia similar to the changes seen in Hurler disease are obvious but there is no scaphocephalic deformation of the skull. Actually, the head is brachycephalic and there may be synostosis of the coronal sutures. Gingival hyperplasia becomes very evident. Hepatosplenomegaly is present but mild, hernias are common. Cardiomegaly and heart murmurs are frequent with aortic insufficiency. Corneal opacities are usual. The optic fundi is normal. Hearing is impaired in some patients. Lymphocytes in blood and bone marrow contain cytoplasmic vacuoles. Persistent nasal discharge and repeated respiratory infections are part of the disease. There is no mucopolysacchariduria. The picture of I-cell disease resembles Hurler disease but there are some important differences. The I-cell disease start earlier and is more rapid, neurological dysfunction is more severe, there is a striking gingival hypertrophy, the head is brachycephalic. The blood findings are different and there is no mucopolysacchariduria. Death usually occur between the ages of five and eight years, usually due to congestive heart failure or pulmonary infection. The diagnosis is confirmed biochemically by measuring the activity of lysosomal enzymes in serum and cultured fibroblasts. There is 10 to 20 fold increase in serum beta-hexosaminidase, iduronate sulfatase and arylsulfatase A. There is deficiency in the activity of N-acetylglucosaminyl-1 phophotransferase in cultured fibroblasts or leukocytes, which is the final proof of diagnosis. Prenatal diagnosis is possible. Carrier detection is possible. Treatment has been attempted with bone marrow transplantation in a few patients with improvement of biochemical and somatic abnormalities but neurological status was not improved.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
EB-F. EB-W. Cultured fibroblasts contain numerous inclusions. These inclusions represent large lysosomes filled with mucopolysaccharides and membranous material. Several lysosomal hydrolases are markedly elevated in serum but deficient in fibroblasts. The diagnosis is confirmed biochemically by measuring the activity of lysosomal enzymes in serum and cultured fibroblasts. There is 10 to 20 fold increase in serum beta-hexosaminidase, iduronate sulfatase and arylsulfatase A. There is deficiency in the activity of N-acetylglucosaminyl-1 phophotransferase in cultured fibroblasts or leukocytes, which is the final proof of diagnosis. Prenatal diagnosis is possible. Carrier detection is possible.