Porphyria cutanea tarda (PCT) in a patient with chronic renal failure on haemodialysis.

Porphyria cutanea tarda, diagnosed by reduced levels of red cell uroporphyrin decarboxylase and raised plasma porphyrins, developed in a patient with chronic renal failure due to polycystic kidneys, treated with haemodialysis, who had normal total faecal porphyrins. Haemodialysis did not alter plasma porphyrin levels and we deduced that most of the plasma porphyrins were circulating in high molecular weight protein complexes.

Ehlers-Danlos syndrome presenting as rheumatic manifestations in the child.

Nine patients with Ehlers-Danlos syndrome (EDS) presented with joint complaints. This represented 5% of the new pediatric arthritis patients seen over a 6-month period. All 9 patients had a history of double-jointedness, and 7 had arthralgias associated with increased physical activity. On physical examination all had hypermobile joints, 7 had joint tenderness, but none had joint swelling. Based on the presence of other features including hyperextensible skin, widened scars, and cardiac clicks and murmurs, 8 were categorized as EDS Type II and 1 as EDS Type III. It posed a significant problem because the diagnosis had not been previously entertained before consultation and erroneous diagnosis had been made. Therefore, EDS should be included in the differential diagnosis of polyarthralgia in the child.

Localized scleroderma and idiopathic thrombocytopenia.

Two patients with localized scleroderma who developed thrombocytopenic purpura are reported. In both patients the thrombocytopenia improved after prednisone therapy, and has not recurred in 5 and 8 yr of subsequent observation without steroids. Both patients had a positive antinuclear antibody (ANA) test and 1 had a positive assay for immune complexes by the Clq solid phase radioimmunoassay. Non-immune causes for the lowered platelets were not found. This possible association may add a new, potentially life-threatening dimension to localized scleroderma.

Sex-influenced expression of Madelung's deformity in a family of dyschondrosteosis.

Dyschondrosteosis is a mesomelic form of short stature which occurs in conjunction with a characteristic wrist deformity. Madelung's deformity. A family with dyschondrosteosis had an affected father and two daughters. The affected females had dyschondrosteosis and Madelung's deformity, while the affected males had dyschondrosteosis, but no Madelung's deformity. All affected members had arthralgias. The occurrence of male to male transmission confirms an autosomal dominant inheritance pattern for this disorder.

Maffucci's syndrome: amesenchymal dysplasia and multiple tumour syndrome.

A case of Maffucci's syndrome with cutaneous, bony and neurological complications is reported. The patient had lymphangiomatosis at birth and developed multiple cutaneous haemangiomas and osteochondromas during childhood. She also developed multiple neurological defects, including cranial nerve palsies due to an intracranial osteochondroma. The occurence of mesodermal dysplasias and neoplasias in the Maffucci syndrome is emphasized, and it is suggested that there is a close relationship between this disorder and Ollier's disease (multiple enchondromatosis).

Characterization of procollagen synthesized by matrix-free cells isolated from chick embryo tendons.

The genetic type and molecular structure of the precursor forms of collagen synthesized by matrix-free tendon cells isolated from 17-day old chick embryos were examined by chromatographic and electrophoretic techniques. The [14C]proline-labeled collagenous proteins secreted by the cells resolved on diethylaminoethylcellulose into two peaks, A and B. Both peaks contained type I collagenous proteins since on chromatography on carboxymethylcellulose, after limited pepsin proteolysis, both peaks contained alpha1 and alpha2 chains of collagen in a 2:1 ratio, and cyanogen bromide peptide maps of the 14C-labeled protein in both peaks were similar to cyanogen bromide peptide maps derived from authentic type I collagen. Enzymatic digestion with purified mammalian collagenase demonstrated that the collagen precursor in peak B contained noncollagenous peptide extensions at both the amino- and carboxy-terminal ends of the molecule, while peak A had only carboxy-terminal extension peptides. Although both the amino- and carboxy-terminal extensions incorporated radioactive cystine, only the carboxy-terminal extensions contained interchain disulfide bonds. The carboxy-terminal extensions were also shown to incorporate radioactive tryptophan. Since most of the precursor forms of collagen recovered in the incubation medium chromatographed in peak B, it is concluded that matrix-free tendon cells secrete only type I procollagen with extension peptides at both the amino- and carboxy-terminal ends of the molecule.

Immunologic characterization of the membrane-bound collagen in normal human fibroblasts: identification of a distinct membrane collagen.

Collagen, the major extracellular matrix protein, is also a membrane protein. Two types of collagen are detected on the normal human fibroblast membrane in culture, type I collagen and a new immunologically and chemically distinct collagen, type M (membrane) collagen. Antibodies to type M collagen elicited complement-mediated cytotoxicity, which could be blocked by pretreatment of the cells with bacterial collagenase or the antibody with type M collagen. Pretreatment of the cells with other proteolytic enzymes or the antibody with type I collagen or type III collagen had no effect on this complement-mediated cytotoxicity. Although type I collagen is the major collagen synthesized by normal human fibroblasts type M collagen may be the major cell membrane collagen and may be a major cell membrane component.

Defects in the biochemistry of collagen in diseases of connective tissue.

The collagens are the major structural glycoproteins of connective tissues. A unique primary structure and a multiplicity of post-translational modification reactions are required for normal fibrillogenesis. The post-translational modifications include hydroxylation of prolyl and lysyl residues, glycosylation, folding of the molecule into triple-helical conformation, proteolytic conversion of precursor procollagen to collagen, and oxidative deamination of certain lysyl and hydroxylysyl residues. Any defect in the normal mechanisms responsible for the synthesis and secretion of collagen molecules or the deposition of these molecules into extracellular fibers could result in abnormal fibrillogenesis; such defects could result in a connective tissue disease. Recently, defects in the regulation of the types of collagen synthesized and in the enzymes involved in the post-translational modifications have been found in heritable diseases of connective tissue. Thus far, the primary heritable disorders of collagen metabolism in man include lysyl hydroxylase deficiency in Ehlers-Danlos syndrome type VI, p-collagen peptidase deficency in Ehlers-Danlos syndrome type VII, decreased synthesis of type III collagen in Ehlers-Danlos syndrome type IV, lysyl oxidase deficency in S-linked cutis laxa and Ehlers-Danlos syndrome type V, and decreased synthesis of type I collagen in osteogenesis imperfecta.

Patients with Ehlers-Danlos syndrome type IV lack type III collagen.

One of the genetically distinct collagens (type III) normally found in skin, aorta, and intestine is missing from the tissues of patients with the Ehlers-Danlos syndrome type IV. While skin fibroblasts from other individuals synthesize both types I and III collagen. Ehlers-Danlos syndrome IV cells synthesize only type I. These results suggest that the fragile skin, blood vessels, and intestines of Ehlers-Danlos syndrome IV patients result from an absence of type III collagen.

Identification of the collagenous proteins synthesized by cultured cells from human skin.

Cells cultured from human skin synthesize precursor forms of types I and III collagens. After denaturation and reduction, the polypeptide chains obtained from these molecules had molecular weights estimated to be 140,000 and 120, 000. The larger chains, the pro alpha chains, are believed to be derived from the original precursor molecules. The smaller chains arise from altered forms, p-collagens, that may be normal intermediates in the conversion of both procollagens to collagens I and III.

Abnormal collagen metabolism in cultured cells in osteogenesis imperfecta.

Cells obtained from normal human skin synthesize predominantly type I collogen in culture. Cells obtained from the skin of an infant with a severe form of osteogenesis imperfecta were found to synthesize as much type III as type I collagen. Decreased synthesis of type I collagen could explain the tissue fragility observed in this case.