Diagnosis of Hurler's syndrome in the hospital laboratory and the determination of its genetic type.

The rare genetically determined disease now known as Hurler's syndrome, characterized by dwarfism, grotesque skeletal deformity, limitation of joint movement, deafness, hepatosplenomegaly, cardiac abnormality, characteristic facies, and perhaps clouding of the cornea and mental retardation (McKusick, 1960), was first described by Hunter (1917). For some years, the substance that accumulates in the tissues in this condition was thought to be a lipid-largely because it disappeared during routine histological processing-and this gave rise to the term lipochondrodystrophy. However, the work of Dorfman and Lorincz (1957) and Meyer, Grumbach, Linker, and Hoffman (1958) showed that mucopolysaccharides were excreted in excess in the urine, and accumulated in the tissues. More recently, Terry and Linker (1964) have shown that the different genetic forms of Hurler's syndrome excrete different patterns of mucopolysaccharide in the urine. Several laboratory tests have been devised to aid the diagnosis of Hurler's syndrome, though none has received universal acceptance. A turbidity reaction between mucopolysaccharides and acidified albumin, developed by Dorfman and Ott (1948) for the assay of hyaluronidase, has been adapted to the examination of urine (McKusick, 1960). Berry and Spinanger (1960) described a paper spot test for Hurler's syndrome, utilizing the metachromatic reaction between sulphated mucopolysaccharides and toluidine blue. Segni, Romano, and Tortorolo (1964) found that the uronic acid content of dialysed urine was higher in cases of Hurler's syndrome than in controls, and suggested this as a diagnostic test. For the haematologist, metachromatic inclusions in polymorphs (Reilly, 1941) and lymphocytes (Muir, Mittwoch, and Bitter, 1963) afford a diagnosis in many cases. Though a combination of these investigations may