Mucolipidosis III is genetically heterogeneous.

Mucolipidosis III (ML III), or pseudo-Hurler polydystrophy, is an inherited childhood disorder characterized biochemically by low activities and abnormal electrophoretic patterns of multiple lysosomal enzymes in fibroblasts. The primary deficiency of ML III has been proposed to be in UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase. However, variation in this enzyme and in other biochemical properties of different ML III lines has been observed. Therefore, we investigated genetic heterogeneity within the disorder by complementation analysis. Heterokaryon cell fractions were generated by fusing together ML III fibroblast lines. When pairs of cells complemented, correction of lysosomal enzyme activities and electrophoretic patterns was observed. Twelve fibroblast lines from 10 sibships were analyzed and three distinct complementation groups were characterized. One complementation group represents the classical ML III disorder. A single cell line identifies a second complementation group. The cell lines comprising a third complementation group have a number of biochemical characteristics different from classical ML III and may represent a genetically distinct disorder.