MUCOLIPIDOSIS IV FOUNDATION - MEDICAL INFORMATION
Mucolipidosis IV - Pathology
Ultrastructural examination reveals striking lysosomal storage inclusions in cells from almost every organ or tissue in the body. These inclusions resemble the membranous cytoplasmic bodies seen in the gangliosidoses, but differ in their localization. In the gangliosidoses, cytoplasmic membranous bodies are not found in liver, spleen, cultured fibroblasts, or dermal epithelial cells. They are prominent in these locations in Mucolipidosis IV. In addition to the cytoplasmic membranous bodies, granulofibrillar material also accumulates, often surrounded by cytoplasmic membranous lamellae with lamellar and granular components blending into one another.
Biochemical analysis of cultured fibroblasts in tissue obtained from brain biopsy reveals elevated ganglioside content. In febroblasts, accumulation especially involves the polysialylated species (gangliosides GDIA and GT). In addition, phospholipids and acidic mucopolysacchrides accumulate within cultured bibroblasts. The fundamental enzyme defect in this desease that leads to accumulation of this diverse group of storage compounds is unknown. It had been proposed that the fundamental defect was a deficiency of a ganglioside sialidase which is distinct from the sialidase which cleaves water-soluble oligosaccharides that is deficient in sialidosis. The ganglioside sialidase cleaves sialic acid from a variety of gangliosides, including the monosialoganglioside GM3 and the disialoganglioside GDIA. However, growing evidence indicates that ganglioside sialidase deficiency is not the primary defect in ML IV. It has also been proposed that an appripriate term for Mucolipidosis type IV is sialolipidosis. This was meant to distinguish this disorder eponymically from sialidosis, which is due to a defect in the dialidase that hydrolyzes sialo-oligosaccharide. The disease is transmitted as an autosomal recessive trait. A higher frequency of patients of Ashkenazi Jewish origin has been noted, although several non-Jewish patients have also been described.
...The disease is characterized by severe visual impairment and psychomotor retardation. Corneal clouding is a characteristic clinical feature and is the initial diagnostic sign in most patients. The age of onset of corneal clouding varies from infancy to 5 years. However, retinal degeneration is also present and often produces visual impairment within the first year of life before corneal opacities are sufficient to impair vision. Psychomotor retardation is present in all patients, with psychomotor skills being retarded to approximately the 1-year level. After the initial retardation in motor and language function, little further psychomotor deterioration is apparent, even in patients with life spans beyond 10 years of age. In fact, some patients exhibit slow but continuous improvement in cognitive language and motor function with time. However, most patients remain severly retarded, exhibiting both mental and growth retardation.
Source: The Metabolic Basis of Inherited Disease, 2nd edition.
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