The best known of this group are Hunter’s and Hurler’s syndromes. In these conditions there is inability to metabolize certain mucopolysaccharides, resulting in accumulation and storage of these substances in various body organs and tissues and excretion of some stored material in the urine.

Hurler’s syndrome. Hurler’s syndrome is caused by deficiency of the enzyme alpha-L-iduronase. Affected infants appear normal for the first 6-8 months of life but then develop skeletal abnormalities (short stature, kyphosis, broad hands, saddle-shaped deformity of the bridge of the nose), clouding of the cornea leading to severe loss of vision, a tendency toward umbilical and inguinal hernias, hepatosplenomegaly, thick tongue, and mental retardation. Diagnosis of Hurler’s syndrome (or any of the mucopolysaccharide disorders) can be made by chromatographic identification of the mucopolysaccharide excreted in the urine. A more conclusive diagnosis can be established by tissue culture of skin biopsy fibroblasts with assay for the specific enzyme involved.

Other connective tissue disorders. There is an important group of hereditary connective tissue disorders, including Marfan’s syndrome, Ehlers-Danlos syndrome, and osteogenesis imperfecta, for which no laboratory screening test or specific diagnostic biochemical test is available. Diagnosis is made by clinical criteria, in some cases supported by x-ray findings.