I-CELL DISEASE (MUCOLIPIDOSIS TYPE II)

 I-cell disease is an inherited lysosomal storage disorder.

The biochemical defect in the I-cell disease involved the first step in addition of mannose-6-phosphate to lysosome proteins. The enzyme that catalyzed this reaction is uiridine disphospho (UDP)-N acetylglicosamine: N-acetylglicosaminyl-1-phosphotransferrase. Deficiency of this enzyme prevents the addition of the mannose-6-phosphate recognition marker because the lysosomal enzyme are modified in the Golgi apparatus before being transported to lysosome; therefore lysosome enzyme can not be endocytosed into the lysosome for normal processing and use.

The functional deficiency of lysosomal enzyme result in abnormal cell architecture, the characteristic finding en I-cell disease is abnormal vacuolization or inclusions that appear in the cytoplasm, especially in fibroblasts.

Finding:

Growth failure and failure to thrive.

Developmental delay is severe.

Coarse facial feature: high, narrow forehead, puffy eyelids, epicanthal folds, flat nasal bridge, anteverted nares, long philtrum, prominent gingival hyperplasia and macroglossia.

Musculoskeletal abnormalities: congenital hips dislocation, joint stiffness and claw hand deformities, lumbar gibbous deformity and kyphoscoliosis.

Restricted joint movement

Clouded corneas (may be clear or hazy).

Frequent upper respiratory tract infection.

High plasma levels of lysosomal enzymes.

Often fatal in childhood. Death from pneumonia and congestive cardiac failure usually occurs within the first decade of life.

Although psychomotor retardation is a major manifestation of this disease, the pathologic findings in CNS tissue are not as striking as in other organs. Among reported finding is the presence of lamellar bodies in spinal ganglia neurons and in anterior horn cells, however, these finding are not consistent in all patients. Vacuolization of peripheral Schwan cell is minimal but not enough to impair normal myelination. The most severely affected system is the skeletal system, muscular tissue including cardiac muscle, other like a renal glomerular podocytes and the fibroblasts of the liver’s periportal space. Hepatocytes and Kupffer cell are not affected.

I-cell disease is rare disorder that has no race or sex predilection, is an inherited autosomal recessive.

The clinical manifestations can be present at birth or in the first month of life.

Available treatment for I-cell disease remains limited; bone marrow transplantation has been attempted in small number of patient.

 Efforts can be made to maximize overall health maintenance. Because these children have progressive failure to thrive nutritional supplementation may be beneficial; promptly treat recurrent respiratory infections with antibiotic.