Dysostosis multiplex

Genetic defects in the degradation of glycoproteins are representative of lysosomal storage disorders. Each disease is caused by a deficiency of a lysosomal hydrolase, accumulation and urinary excretion of substrates, a progressive clinical course and considerable phenotypic variation. These disorders also manifest the clinical symptoms normally associated with genetic mucopolysaccharidoses, namely coarse facies, dysostosis multiplex and/or ocular involvement. 

The infantile form (ISSD) represents the most severe form of the disease, with failure to thrive, severe psychomotor retardation, visceromegaly with ascites, dysostosis multiplex. Onset is at birth or in utero and is followed by early death, usually within the 1st year [6]. 

MPS IH Hurler Corneal clouding, dysostosis multiplex, organomegaly, heart disease, mental retardation, death in childhood a-L-Iduronidase Dermatan sulfate, heparan sulfate... 

MPS VI Maroteaux-Lamy Dysostosis multiplex, corneal clouding, normal intelligence survival to teens in severe form milder forms known to exist V-Acetylgalactosamine 4-sulfatase (arylsulfatase B) Dermatan sulfate... 

MPS VII Sly Dysostosis multiplex, hepatosplenomegaly wide spectrum of severity, including hydrops fetalis and neonatal form j8-Glucuronidase Dermatan sulfate, heparan sulfate, chondroitin 4-, 6-sulfates... 

Mental and motor deterioration accumulation of mucopolysaccharides is as significant as accumulation of gangliosides invariably fatal autosomal recessive blindness, cherry red macula (30%) hepatosplenomegaly vacuolated lymphocytes startle response to sound, dysostosis multiplex. 

Type VII /3-D-Glucuronidase deficiency (more than one allelic form ) Hepatosplenomegaly, dysostosis multiplex, white cell inclusions, mental retardation Homozygous for mutant gene at /3-D-glucuronidase locus Chondroitin 4-sulfate, chondroi-tin 6-sulfate -D-Glucuronidase... 

Skeleton Dysostosis multiplex Kyphosis Short stature + ++ +++... 

Fig. 19.2. Clinical approach to the diagnosis of oligosaccharidoses and related lysosomal disorders with early (infantile) onset. Associated with CNS involvement of various types. Facial dysmorphism and/or skeletal (vertebral) involvement suggestive of dysostosis multiplex. Bold conditions associated with abnormal oligosacchariduria italics conditions associated with abnormal mucopolysacchariduria. The percentage of patients showing macular cherry-red spot (when present) is indicated in parentheses. Absence of visceromegaly...

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