No abstract

Lysosomal acid hydrolases were determined in established lymphoblastoid cell lines, transformed in vitro by Epstein-Barr virus (EBV) from lymphocyte-rich cell populations isolated from the peripheral blood of patients with genetic lysosomal storage diseases--Hurler syndrome, Scheie syndrome, GM1-gangliosidosis type 1 and type 2, Tay-Sachs disease, and I-cell disease--and from obligate heterozygotes for these diseases. The respective enzyme activity was undectectable in lymphoblastoid cells from the patients, but not from controls. Obligate heterozygotes could not always be distinguished from controls in lymphoblastoid cells as well as in leukocytes. These results suggest that established lymphoblastoid cell lines are useful material for the enzymatic study of genetic lysosomal storage diseases.

Clinical, biochemical, and electron microscopic studies are presented in two brothers with Niemann-Pick disease. The clinical features include hepatosplenomegaly and mental retardation without any other neurological signs. Roentgenograms of the chest showed bilateral diffuse reticular infiltration. The amounts of sphingomyelin and cholesterol in liver were increased, and sphingomyelinase activities in both liver and skin fibroblasts were markedly reduced in Case 1. Numerous foam cells and myelin figures were observed in the liver, kidneys, bone marrow, and lymph nodes on electron microscopical examination. These cases were regarded as a variant of Niemann-Pick disease from our investigations as they have mental retardation as an exceptional symptom when they are diagnosed as type B.

On DEAE cellulose column chromatography, alpha-L-iduronidase in cultured skin fibroblasts was resolved into two distinct components, forms A and B. They had similar Km values for 4-methylumbelliferyl-alpha-L-iduronide, but differed in pH optima and thermal stability. Form B was more heat-stable than form A. Residual alpha-L-iduronidase activity in Hurler fibroblasts was heat-stable, while that in Scheie fibroblasts was heat-labile, and moreover, that in Hurler-Scheie compound fibroblasts lay intermediate between Hurler and Scheie syndromes. These findings demonstrated that Hurler syndrome, Scheie syndrome and Hurler-Scheie compound were enzymatically distinguishable.