Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Dyggve-Melchior-Clausen (DMC) syndrome includes short stature, dwarfism, mental retardation, and skeletal abnormalities especially in the spine and the extremities resembling the findings in the mucopolysaccharidoses. A particular abnormality is the "lace border" found on radiological examination of the iliac crest. The three original cases have been followed for 15--20 years and the course is characterized by increasing mental retardation and motor disability whereas the "lace border" is less pronounced than before. A survey of 17 other cases is given and similarities and differencies to the mucopolysaccharidoses are pointed out. Patients with the DMC syndrome have been suggested to be deficient in an enzyme cleaving glycoprotein-acid mucopolysaccharide (AMP) linkage. We have previously found in DMC patients, an abnormal excretion of urinary AMP's of which some were undersulfated and some were oversulfated. Lysosomal acid proteinase, i.e., cathepsin D and neutral proteinases: elastase and cathepsin G were found to be normal in DMC patients. However, alfa2-macroglobulin in serum was raised. This increase may cause an inhibition of the neutral proteinases. An increased level of chondroitin sulfate N-acetylgalactosamine-6-sulfate-sulfatase and decreased enzymic levels of aryl sulphatase A and B (assayed with p-nitrocatecholsulfate as a substrate) were found in leucocytes of DMC patients. Metabolic studies have revealed an unbalanced incorporation of glycoprotein AMP-precursors in DMC lymphocytes. All in all the data suggests the DMC syndrome to be an inborn error of glycoprotein-AMP-metabolism.
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PMID:The Dyggve-Melchior-Clausen (DMC) syndrome. A 15 year follow-up and a survey of the present clinical and chemical findings. 57 40

Dyggve-Melchior-Clausen (DMC) is a rare autosomal-recessive disorder characterized by the association of a progressive spondylo-epi-metaphyseal dysplasia and mental retardation ranging from mild to severe. Electron microscopy studies of both DMC chondrocytes and fibroblasts reveal an enlarged endoplasmic reticulum network and a large number of intracytoplasmic membranous vesicles, suggesting that DMC syndrome may be a storage disorder. Indeed, DMC phenotype is often compared to that of type IV mucopolysaccharidosis (Morquio disease), a lysosomal disorder due to either N-acetylgalactosamine-6-sulphatase or beta-galactosidase deficiency. To date, however, the lysosomal pathway appears normal in DMC patients and biochemical analyses failed to reveal any enzymatic deficiency or accumulated substrate. Linkage studies using homozygosity mapping have led to the localization of the disease-causing gene on chromosome 18q21.1. The gene was recently identified as a novel transcript (Dym) encoding a 669-amino acid product (Dymeclin) with no known domains or function. Sixteen different Dym mutations have now been described in 21 unrelated families with at least five founder effects in Morocco, Lebanon, and Guam Island. Smith-MacCort syndrome (SMC), a rare variant of DMC syndrome without mental retardation, was shown to be allelic of DMC syndrome and to result from mutations in Dym that would be less deleterious to the brain. The present review focuses on clinical, radiological, and cellular features and evolution of DMC/SMC syndromes and discusses them with regard to identified Dym mutations and possible roles of the Dym gene product.
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PMID:Recent advances in Dyggve-Melchior-Clausen syndrome. 1546 20