Mucolipidosis II and III: different residual activity of beta‐galactosidase in cultured fibroblasts*

Leroy, Jules; O’Brien, John S.

doi:10.1111/j.1399-0004.1976.tb01608.x

Cited by 21 publications

References 19 publications

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The mucolipidoses: Identification by abnormal electrophoretic patterns of lysosomal hydrolases

et al. 1981

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The human mucolipidoses (ML) are characterized by abnormal activities and abnormal electrophoretic patterns of fibroblast lysosomal hydrolases. These altered mobility patterns can be used to confirm the clinical diagnosis of the four mucolipidoses. The mobility patterns of one nonlysosomal and seven lysosomal enzymes were tested in fibroblasts from two ML I (sialidosis type 2, infantile), fifteen ML II (I-cell disease), eight ML III (pseudohurler polydystrophy), and one ML IV patients. A single sialidosis type 2, juvenile, line was also examined. Characteristic mobility patterns were found which identify each of the four mucolipidoses. Both the ML I and sialidosis type 2 juvenile lines displayed anodal mobility patterns, but distinct differences between the two disorders were observed. Lysosomal hydrolases from ML II lines demonstrated reduced activities or had altered mobilities. Differing electrophoretic patterns demonstrated the presence of at least two groups within the clinical phenotype diagnosed as ML II, indicating heterogeneity. The ML III lines showed normal electrophoretic patterns for most lysosomal hydrolases. The ML IV line expressed normal mobilities for every enzyme studied, with a single exception. The electrophoretic patterns of only beta-hexosaminidase, acid phosphatase-2, alpha-galactosidase, and esterase A4 were sufficient to identify and distinguish the different mucolipidosis types. Electrophoretic variation was also seen in liver but not kidney extracts from three ML II patients. beta-Hexosaminidase and alpha-mannosidase B secreted into the medium by ML II and ML III fibroblasts had mobility patterns different from normal and from their intracellular patterns. These data suggest that the mucolipidoses are genetically distinct with heterogeneity within them.

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The mucolipidoses: Identification by abnormal electrophoretic patterns of lysosomal hydrolases

et al. 1981

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Genetic heterogeneity of I‐cell disease is demonstrated by complementation of lysosomal enzyme processing mutants

Shows¹,

Mueller²,

Honey³

et al. 1982

Am. J. Med. Genet.

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I-cell disease (mucolipidosis II) is a fatal childhood disorder affecting the expression of multiple lysosomal acid hydrolases. The disorder is characterized by clinical and biochemical heterogeneity which may reflect different mutants with a similar phenotype. Genetic complementation studies demonstrating genetic heterogeneity within this disorder are described utilizing cultured fibroblasts from 11 different patients. Fibroblasts from I-cell disease (ICD) and from five different lysosomal storage diseases with single structural gene enzyme deficiencies were fused in different combinations, and fractions enriched for multinucleated heterokaryons were isolated and tested for acid hydrolase activity and electrophoretic mobility. In fusions of ICD fibroblasts and various single lysosomal enzyme-deficient fibroblasts, the activity of the deficient enzyme and of the other ICD hydrolases were restored, demonstrating that ICD is not a lysosomal enzyme structural gene defect and that the ICD defect, and not just the single enzyme deficiency, is corrected. In fusions involving only I-cell fibroblasts, at least two complementation groups were identified by the recovery of activities of all lysosomal enzymes tested in heterokaryons. These results demonstrate the existence of genetic heterogeneity within the disorder and suggest that different mutations can result in the I-cell clinical and biochemical phenotype. The data support an altered post-translational processing of lysosomal enzymes as the cause of ICD and suggest that at least two genes participate in this pathway.

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Glycoprotein Storage Diseases and the Mucopolysaccharidoses

Dawson

1979

Complex Carbohydrates of Nervous Tissue

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Mucolipidosis II and III: different residual activity of beta‐galactosidase in cultured fibroblasts*

Cited by 21 publications

References 19 publications

The mucolipidoses: Identification by abnormal electrophoretic patterns of lysosomal hydrolases

The mucolipidoses: Identification by abnormal electrophoretic patterns of lysosomal hydrolases

Genetic heterogeneity of I‐cell disease is demonstrated by complementation of lysosomal enzyme processing mutants

Glycoprotein Storage Diseases and the Mucopolysaccharidoses

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