Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
7933581 [Autoantibodies associated with vasculitis]. 1994 Aug A variety of autoantibodies have been associated with vasculitis, including that to neutrophils or to endothelial cells. Anti-neutrophil cytoplasmic antibodies (ANCA) have been described as sensitive and specific markers for active Wegener's granulomatosis (WG). ANCA in WG produces a characteristic cytoplasmic staining pattern (cANCA) and are directed against proteinase 3 (PR3-ANCA). PR3-ANCA occur in more than 90% of patients with extended WG, in 75% of patients with limited WG without renal involvement and in some 40% to 50% of patients with vasculitic overlap syndrome such as microscopic polyarteritis. Change in levels of cANCA precede disease activity and may be used as guidelines for treatment. Antibodies producing a perinuclear staining of ethanol-fixed neutrophils (pANCA) occur in a wide range of disease. They are directed against different cytoplasmic constituents of neutrophils. Among these, antibodies to myeloperoxidase (MPO-ANCA) are found in patients with idiopathic crescentic glomerulonephritis, the Churg-Strauss syndrome, polyarteritis nodosa and vasculitic overlap syndromes. Anti-endothelial cell antibodies (AECA) have been described in various autoimmune (systemic lupus erythematosus, scleroderma, rheumatoid arthritis) and vasculitic disorders (WG, polyarteritis nodosa, Kawasaki syndrome). They have been implicated in the pathogenesis of vascular injury common to these disorders.
7848317 HLA type as a predictor of mixed connective tissue disease differentiation. Ten-year clini 1995 Feb OBJECTIVE: To determine any clinical or genetic markers of differentiation and outcome in a previously described cohort of 46 patients with mixed connective tissue disease (MCTD). METHODS: Patients were clinically evaluated, chart notes reviewed, and HLA subtyping and immunology profiles performed where possible. Eleven had died and 7 were lost to followup. RESULTS: MCTD had differentiated into systemic lupus erythematosus in 12 patients and into systemic sclerosis in 13. The latter was associated with HLA-DR5 (P = 0.038), and nondifferentiation was associated with HLA-DR2 or DR4 (P = 0.007). Three HLA-DR4 positive patients had MCTD that evolved into rheumatoid arthritis. Erosive and/or deforming arthritis was associated with HLA-DR1 or DR4 (P = 0.015). HLA-DR3 was associated with interstitial lung fibrosis (P = 0.044) and keratoconjunctivitis sicca (0.001 < P < 0.01). Severe Raynaud's phenomenon predicted higher mortality (0.01 < P < 0.05). CONCLUSION: We suggest that MCTD is, for most patients, an intermediate stage in a genetically determined progression to a recognized connective tissue disease. Those whose disease remains undifferentiated might be considered a distinct subset.
7797266 Polymorphism of the MHC class II Eb gene determines the protection against collagen-induce 1995 Collagen-induced arthritis (CIA) is an animal model of auto immune polyarthritis, sharing similarities with rheumatoid arthritis (RA). Paradoxally, susceptibility to mouse CIA is controlled by the H2A loci (DQ homologous) while RA is linked to HLA.DR genes (H2E homologous). We recently showed that the E beta d molecule prevents CIA development in susceptible H2q mice. We addressed the question of whether H2Eb polymorphism will influence CIA incidence as HLA.DRB1 polymorphism does in RA. In F1 mice, only H2Ebd and H2Ebs molecules showed protection. Using recombinant B10.RDD (Ebd/b) mice, we found that CIA protection was mediated by the first domain of the E beta d molecule. Using peptides covering the third hypervariable region of the E beta chain, we found a perfect correlation between presentation of E beta peptides by the H2Aq molecule and protection on CIA. Therefore, the mechanism by which H2Eb protects against CIA seems to rely on the affinity of E beta peptides for the H2Aq molecule.
8456672 MR imaging of the knee: can changes in the intracapsular fat pads be used as a sign of syn 1993 Apr OBJECTIVE: Synovial proliferation is difficult to detect on MR images when joint effusions are present. The objective of this study was to assess the efficacy of MR changes in intracapsular fat pads (prefemoral, quadriceps, Hoffa's) as a sign of synovial proliferation in patients with knee effusions. MATERIALS AND METHODS: MR images were obtained in 70 patients with knee effusions. An effusion was considered present if the suprapatellar bursa was distended 1 cm in anterior to posterior diameter on T2-weighted sagittal images. The experimental group consisted of 32 patients with proliferative effusions (effusions associated with synovial proliferation) diagnosed on the basis of histologic or microbiologic data or strict rheumatologic criteria. This group comprised 11 patients with pigmented villonodular synovitis, six with rheumatoid arthritis, one with psoriatic arthritis, three with hemosideric arthritis, and 11 with septic arthritis. The control group comprised 38 subjects with knee effusions who had no arthroscopic evidence of synovial proliferation. After determining the MR criteria of proliferative effusion, two observers who had no knowledge of these cases evaluated abnormalities of the intracapsular fat pads seen on sagittal intermediate-weighted midline MR images. RESULTS: Characteristic changes in the fat pads were noted on MR images in patients with proliferative synovial effusions. Scalloping or truncation of the prefemoral fat pad was 77% sensitive and 95% specific as a predictor of proliferative effusion. Defects and displacement of Hoffa's fat pad had a sensitivity of 57% and a specificity of 99%, and nonvisualization or irregular margins of the quadriceps fat pad had a sensitivity of 61% and a specificity of 100%. CONCLUSION: Characteristic changes in intracapsular fat pads seen on MR images of patients with proliferative effusions can help distinguish these patients from those with effusions without synovial proliferation.
8910772 Induction of a proinflammatory cytokine network by Mycoplasma arthritidis-derived superant 1996 Oct Mycoplasma arthritidis is an arthritogenic organism for rodents, producing a superantigen (MAS). It has been postulated that mycoplasmas or superantigens thereof might play a role in human rheumatoid arthritis. Since M. arthritidis fulfills both, the present study was performed to investigate MAS-specific cytokine induction. Human or murine leukocytes were stimulated with MAS, staphylococcal enterotoxin E (SEE), or lipopolysaccharide (LPS). Cytokines were measured by ELISA, Bioassay, and RT-PCR. The response to MAS in humans was individually restricted, in contrast to the response to SEE or LPS. Furthermore, MAS showed the same capacity for inducing proinflammatory cytokines as interleukin (IL)-1 IL-6, and IL-8 as SEE and LPS. However, MAS showed a significantly decreased capacity to induce the anti-inflammatory cytokine IL-10 and IL-1RA. In mice, the reactivity to MAS was strictly MHC-II restricted, in contrast to that of SEE or LPS. The individual response to MAS in humans might be explained by the difference of the HLA-DR haplotype because H-2-differing mouse strains showed the same discrepancies. MAS induced an overproduction of proinflammatory cytokines, when its ability to induce proinflammatory and anti-inflammatory cytokines was compared with those of SEE and LPS. The individual response may explain an MHC linkage, and the failure to induce anti-inflammatory cytokines may be the reason for a chronic disease in contrast to acute inflammation.
1335953 [Infections with herpesvirus 6--really only "exanthema subitum"? Part 2: Rare or unknown d 1992 Nov 30 The human herpes virus 6 (HHV 6) may induce not only the wellknown condition of exanthem subitum, but also a number of more common (cf. Part 1) or rare, even previously unknown, clinical manifestations. Part 2 of this paper deals with the more rarely observed manifestations. These include complications of ARD (sinusitis, otitis media, bronchial pneumonia) hepatitis, encephalitis or Pfeiffer's disease (mononucleosis-like syndrome). In individuals with a relevant disposition (genetic HLA/DR type?) initiation or (re-)activation of rheumatoid arthritis (JCA = juvenile chronic arthritis) or chronic iridocyclitis may occur. Although, on account of the high prevalence of vaccination in our population (approximately 95%), prenatal infections are extremely rare, they may manifest in a severe "septic" form (fatalities have occurred) or may lead to neurological deficits (comparable with cytomegalovirus infection). To date, no specific therapy (e.g. gammaglobulin, virostatics) or reliable preventive measures (e.g. vaccination) are available.
1540041 The cervical spine in patients with psoriatic arthritis: a clinical, radiological and immu 1992 Jan The radiological changes of the cervical spine were evaluated in 57 patients with psoriatic arthritis and were correlated with clinical, radiological, and immunogenetic features of the disease. Forty patients (70%) showed radiological evidence of the cervical spine being affected by the disease. Two patterns of cervical spine abnormalities were noted. Fifteen patients (26%) had erosive and/or subluxing cervical rheumatoid like lesions; 25 patients (44%) had a more frequently reported pattern similar to ankylosing spondylitis. Although subaxial subluxations were the most frequently observed cervical abnormalities (53%) in the inflammatory subgroup, none of the patients studied had cord compression. Ankylosing cervical spine disease was the only form of axial involvement in nine (36%) of 25 patients with the ankylosing form of psoriatic arthritis. All of these patients had peripheral disease and were B27 negative. Predictors of cervical spine disease patterns were considered using clinical, demographic, and radiological features and HLA antigens. The results of a multivariate analysis showed that the best predictors of inflammatory cervical spine disease are the presence of HLA-B39 and HLA-DR4 antigens, radiocarpal erosions, and the absence of the HLA-DR5 antigen.
7588951 A survey of radiation synovectomy in Europe, 1991-1993. 1995 Sep The prevalence of radiation synovectomy practice is unknown. As new particulate radiopharmaceuticals offering many potential advantages are being developed, it seems prudent to appraise the extent, frequency and variation in radiation synovectomy practice. We have evaluated radiation synovectomy practice in Europe over the period 1991-1993 by means of a postal questionnaire. More than 2300 European members of the European Association of Nuclear Medicine were questioned about the number of treated patients and joints, disease prevalence in their patients and the use of radiopharmaceuticals. Overall, 119/490 (24%) of centres replying to the survey practised radiation synovectomy during the 3 years. There were 13,450 different joint injections in 8578 patients. Rheumatoid arthritis was the most prevalent disease in patients treated (71%) and the most frequently treated joints were knee (46%) and finger joints (20%). Eight different radiopharmaceuticals were employed. Yttrium-90 colloids were most frequently and widely (100/119 centres) used, mainly employed for knee synovectomy but were also used to treat most appendicular joints. Erbium-169 colloid was almost exclusively used to treat finger joints (31/33 centres). Corticosteroid was routinely co-injected in 36/60 (60%) centres. Radiation synovectomy was widely practised throughout Europe during 1991-1993. There are variations in practice illustrated by the diversity of treated arthritides and injected joints and by the use and application of different radiopharmaceuticals.
7927763 Comparison of the antibody responses to the 77 Klebsiella capsular types in ankylosing spo 1994 Nov The production of antibodies to Klebsiella capsular polysaccharides was measured in sera from either HLA-B27-positive (HLA-B27+) or HLA-B27-negative (HLA-B27-) patients with classical ankylosing spondylitis (n = 54). These sera were compared with sera from patients with various rheumatic diseases (n = 82) and HLA-B27+ or HLA-B27- healthy individuals (n = 85). All sera were analyzed by means of an enzyme-linked immunosorbent assay specific to each of the 77 Klebsiella serotypes. The sera from HLA-B27+ patients with ankylosing spondylitis showed a significantly higher antibody frequency to the capsular types K26, K36, and K50 than the sera from HLA-B27- ankylosing spondylitis patients, patients with psoriatic arthritis, systemic lupus erythematosus, rheumatoid arthritis, or reactive arthritis after Yersinia enterocolitica infection, or healthy controls (P < 0.02). The antibodies were of the immunoglobulin G type. No significant antibody response to the other 74 Klebsiella serotypes, noncapsulated mutants of K26, K36, and K50, or preparations of Citrobacter, Serratia, Hafnia, or Morganella spp. or Streptococcus pneumoniae could be detected. The results might suggest a specific association between these capsular types and HLA-B27+ ankylosing spondylitis and might imply their predominance in this disease.
18475473 Bacterial lipopolysaccharide potentiates type II collagen-induced arthritis in mice. 1992 Collagen-induced arthritis (CIA) is an immunologically relevant animal model of human rheumatoid arthritis. Studies comparing the disease incidence in genetically susceptible male and female DBA/1LacJ mice demonstrated that under low density/low stress housing conditions, female mice had earlier onset (day 35) and higher disease incidence (25%) than the male mice (17% at day 49) when immunized with bovine type II collagen. A single subcutaneous or intraperitoneal injection of bacterial lipopolysaccharide (LPS) 17-24 days after collagen immunization greatly potentiated this standard CIA model in a dose related manner. 20-40 mug of LPS accelerated the onset of disease from day 35 to day 21 and exacerbated the clinical severity score from 0.27 to 2.00 at day 42. A similar administration of 6 mug of recombinant interleukin-beta produced a comparable potentiated CIA model. The acute phase protein, serum amyloid P (SAP), was elevated in the serum at day 26 to 440 mug ml(-1) for the LPS potentiated CIA mice compared to 65 mug ml(-1) in the non-potentiated immunized CIA mice. There was a significant correlation (r = 0.78) between SAP levels and disease expression in the LPS treated CIA mice. The rapidity and uniformity of disease expression in this LPS potentiated CIA model will allow more and different drugs to be evaluated with a smaller number of animals.
8181963 Polymorphism of human major histocompatibility complex-encoded transporter associated with 1994 Jan The TAP1 and TAP2 genes encode a peptide transporter supplying peptides for binding to HLA class I molecules. Both genes are located in the class II region of the HLA complex and are polymorphic. Here we report the distribution of TAP alleles in a group of 285 JRA patients (including various subsets), 165 random controls, and 82 DR8-positive controls. We found a pronounced increase of TAP1B and TAP2C/D in patients, compared with controls. The difference was, however, mainly secondary to a strong linkage disequilibrium between these TAP alleles and DR8, which is significantly increased in JRA. When we compared patients and controls after stratification for DR8 the differences decreased, although an increase of TAP1B in DR8-negative patients remained significant. We conclude that a primary association of JRA with given TAP allels cannot explain the HLA class II associations in JRA. However, we cannot exclude the possibility that TAP1B acts as an additive susceptibility factor in JRA.
8496873 Adenohypophyseal and sex hormones in pediatric rheumatic diseases. 1993 Apr Studies in adults with systemic lupus erythematosus (SLE) have shown normal estrogen and lowered androgen levels in serum and abnormal metabolism of estrogen. In our prospective study we tested the hypothesis that one or more of the following factors account for the increased incidence of SLE and pauciarticular juvenile rheumatoid arthritis (JRA) in females: (a) increased estrogen; (b) decreased androgen and (c) increased estrogen receptor in the peripheral blood mononuclear cells (PBMC). Serum and PBMC were collected from 51 healthy children (36 M: 20 F), 17 with JRA (all female) and 37 with SLE (11 M: 26 F). Estrogen receptor was measured in cytosol from PBMC using monoclonal antibody to estrogen receptor and solid phase enzyme immune assay. Serum levels of estrogen, androgen, prolactin, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured using standard radioimmunoassay. There were no significant differences in serum levels of estrogen and prolactin between healthy children and patients. Free androgen was lower in postpubertal boys and girls with SLE compared to healthy children. FSH and LH levels were higher in postpubertal boys and girls with SLE compared to healthy individuals. This trend, while not reaching statistical significance, was supported by a higher percentage of female patients with SLE and abnormal serum levels of FSH (p = 0.001), LH (p = 0.004) and prolactin (p = 0.001). The results of these preliminary studies suggest that the role of prolactin, FSH and LH in rheumatic diseases deserves further study.
7821336 Arthrotec: a therapeutic option in the management of arthritis. 1993 Arthrotec (Searle) is a new concept in NSAID therapy that provides powerful anti-inflammatory efficacy with enhanced upper GI safety. Arthrotec comprises an enteric-coated core of diclofenac sodium (50 mg) surrounded by a mantle of misoprostol (200 mcg). Two multicentre trials evaluated the efficacy of Arthrotec in rheumatoid arthritis (RA) and osteoarthritis (OA) patients who were randomised to receive either Arthrotec or diclofenac. The results of all arthritis assessments showed Arthrotec to be as effective as diclofenac in treating the signs and symptoms of RA and OA. Two endoscopic studies compared the antiarthritic efficacy and gastroduodenal safety of Arthrotec and diclofenac. In a 12-week study of RA patients, the antiarthritic efficacy of Arthrotec was equivalent to diclofenac; in addition, 60% fewer patients taking Arthrotec experienced ulcers than did those taking diclofenac (4.4% Arthrotec vs 11.1% diclofenac: P = 0.034). In a 4-week study of OA patients, Arthrotec's efficacy was equivalent to that of diclofenac and the Arthrotec group developed no ulcers, while 3.6% of the diclofenac group had ulcers (P = 0.015). In a trial conducted to compare the efficacy and upper gastroduodenal safety of Arthrotec with those of piroxicam and naproxen, patients with OA received either Arthrotec BID piroxicam 10 mg BID, or naproxen 375 BID for 4 weeks. Arthritis assessments showed Arthrotec to be at least as effective as piroxicam and naproxen in treating OA. Post-treatment endoscopy data indicated that gastroduodenal ulcers developed in 1.5% of patients receiving Arthrotec, 10.3% of patients receiving piroxicam, and 8.6% patients in the naproxen group.(ABSTRACT TRUNCATED AT 250 WORDS)
8678056 High binding of immunoglobulin M kappa rheumatoid factor from type II cryoglobulins to cel 1996 Apr In our previous experimental work we suggested that the frequent nephritogenicity of type II cryoglobulins could depend on a particular affinity of the immunoglobulin (Ig) M kappa rheumatoid factor (RF) component for mesangial matrix. Since cellular fibronectin (cFN) in the human kidney is mainly represented in glomerular mesangium, we studied the binding capacity to cFN of IgM kappa RFs from type II cryoglobulins compared with other different monoclonal and polyclonal IgM and IgM RFs. We purified 13 IGM kappa from human IgM kappa/IgG cryoglobulins, eight monoclonal IgM from patients with Waldenström's macroglobulinemia, nine polyclonal IgM from normal donors, and eight polyclonal IgM RFs from patients with rheumatoid arthritis. Purified IgM were used at the same concentration in enzyme-linked immunosorbent assay (ELISA) on cFN-coated plates. All the cryoglobulin IgM showed high specific binding to cFN while IgM from Waldenström's macroglobulinemia, normal IgM, and polyclonal IgM RFs had low or absent binding. These data were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cFN followed by Western blot analysis with purified IgM. The IgM kappa binding to cFN persisted using IgM kappa monomers, and was inhibited by cFN but not by plasma FN in a specific inhibition test. Further enzyme-linked immunosorbent assay studies showed that cryoglobulin IgM kappa RFs are still able to bind IgG in a dose-dependent manner once linked to solid-phase cFN. The data suggest that the affinity of cryoglobulin IgM kappa RFs for immobilized cFN could be involved in the particular high nephritogenicity of type II cryoglobulins and might lead to in situ immune complex formation.
7516557 Extraction of neuropeptides from joint tissue for quantitation by radioimmunoassay. A stud 1994 The feasibility of extracting neuropeptides from rat knee joints for quantitation by radioimmunoassay was tested. The investigation, based on 25 adult Lewis rats, focused on substance P, calcitonin gene-related peptide, neuropeptide Y, and vasoactive intestinal polypeptide. The relative recovery of the peptides in different extraction media was assessed Both knee joints including the articulating epiphysis were dissected and cut into small pieces. The series was divided into five subgroups, 10 joints in each, for extraction in five different media: 1) 1 M acetic acid in 4% EDTA, 2) 2 M acetic acid in 4% EDTA, 3) neutral water in 4% EDTA, 4) 2 M acetic acid in 4% EDTA and 95% alcohol, and 5) 2 M acetic acid without EDTA. Measureable concentrations of the four neuropeptides were reproducibly assessed by RIA. Although all extraction media provided measurable concentrations, 2 M acetic acid in 4% EDTA was found to give the highest overall yield of the four neuropeptides analyzed. Reverse-phase HPLC confirmed that the immunoreactivities assessed by RIA corresponded to the four neuropeptides of interest. Experimental and clinical evidence suggest a neurogenic involvement in the pathophysiology of inflammatory joint disease, e.g., rheumatoid arthritis. The extraction procedure described offers a means of determining neuropeptide concentrations in joint tissue under normal and pathologic conditions by RIA.
7532785 Rheumatoid-factor-reactive sites on CH3 established by overlapping 7-mer peptide epitope a 1995 Jan Polyclonal IgM rheumatoid factors (RF) from ten patients with rheumatoid arthritis and six monoclonal IgM RF were isolated from monomeric IgG affinity columns and studied for their reactivity with the entire CH3 domain of IgG synthesized as overlapping 7-mers using a pin-ELISA assay. All ten polyclonal IgM RF showed similar profiles of reactivity which included peptides with solvent accessible residues PREPQVY (residues 343-349), PQVYTLP (residues 346-352), TLPPRSE (350-356), DGSFFLY (401-407), WQQGNVF (417-423), CSVMHEG (425-430), EGLHNHY (430-436) and KSLSLSP (439-446) of the CH3 domain. Substitution of a neutral glycine or alanine for each residue within these RF-reactive epitopes indicated that tyrosine at position 349, prolines at 343, 346 and 352, glutamine 347, valine 348, threonine 350, leucine 351, arginine 354, aspartic acid 401, tyrosine 407, serine 426, histidine 429, leucine 432, tyrosine 436 and lysine 439 represented important single amino acids within CH3 for RF reactivity. Regions of CH3 primary sequence with and without the single allotype-specific amino acid substitutions of glycine for alanine 431 (Gmx) or aspartic acid for glutamic acid (356) and leucine for methionine (358) (Gma) often showed considerable differences in reactivity with individual polyclonal and monoclonal RF. However, these differences in RF reactivity did not correlate with the individual anti-Gm RF specificity. Assays using monoclonal IgM RF produced from RA synovial B cells or peripheral blood B cells frequently showed a much more restricted spectrum of reactive CH3 epitopes. 7-mer peptides representing RF-reactive sites on CH3 preincubated with polyclonal IgM RF showed strong inhibition (55-66%) of RF binding to whole IgG on the ELISA plate. These studies indicate that it is possible to define portions of the IgG CH3 domain participating in the reaction with IgM RF using reactive epitope-mapping with sequential linear peptides derived from the primary IgG CH3 sequence.
8893718 Atlantoaxial degenerative articular cysts. 1996 Nov Cysts associated with spinal joints are not a common cause of neurological symptoms. The authors report a series of five patients with cysts of the atlantodental articulation and review five additional cases from the literature. The patients ranged from 60 to 85 years of age and included three men and seven women. No patient had evidence of rheumatoid arthritis or previous trauma. The cysts caused ventral cervicomedullary compression, did not enhance on magnetic resonance imaging, and were not associated with widening of the anterior atlantodental interval or osseous degeneration of the dens. All patients improved postsurgery. Fusion was required if a transoral procedure was performed. Patients undergoing posterior decompressions were clinically and radiographically stable after operation.
9004830 [Anti-leukotriene agents: rationale for and prospects of use]. 1996 Oct Leukotrienes (LT) are synthesized from arachidonic acid by several enzymes such as phospholipase A2, 5-lipoxygenase, LTC4 synthase, as a consequence of a wide range of inflammatory stimuli. Leukotrienes seem to play a pivotal role in the maintenance of the inflammatory processes as they exert numerous biological activities, i.e. chemotactic action on polymorphonuclear cells, bronchospastic action, vasodilator and secretagogue effects. Thus, the inhibition of LT activity may result in antiinflammatory action. Several compounds capable of blocking either LT synthesis or LT receptors have recently been developed and clinically tested in different experimental models. In particular, encouraging results have been obtained in the asthma model, but interesting clinical observations have also been performed in psoriasis, ulcerative colitis and rheumatoid arthritis. Although further studies and optimization of this kind of treatment are required, a possible clinical role of LT antagonists as antiinflammatory therapy for selected diseases may be envisaged.
8799023 Preradial myxedema: a case report. 1996 Mar We describe a 51-year-old Chinese woman with a 2-year history of swelling of the right forearm and hand, which gradually became hyperpigmented and indurated. This had the typical features of myxedema. The diagnosis was confirmed on histology. She had a past history of thyrotoxicosis and rheumatoid arthritis for which she had undergone treatment. This case is reported as an unusual location of localised myxedema with a literature review and comment on the treatment options. In Singapore only rare similar cases have been reported in the past.
8759415 [Mucolipidosis type III (case report)]. 1996 Jan A six-year-old boy with mucolipidosis type III or pseudo Hurler polydystrophy is described. The disease is manifested by multiple progressive joint contractures, especially of fingers, presenting as claw hands. The diagnosis of mucolipidosis was established after exclusion of rheumatoid arthritis and mucopolysaccharidosis. In serum and medium of cultured skin fibroblasts, high catalytic activities of several lysosomal enzymes with strikingly decreased values in fibroblast homogenate were found. In most lysosomal diseases gene mutations cause reduced or absent activity of a specific enzyme. In mucolipidosis type III, a basic biochemical disorder is the absence of mannose-6-phosphate, a marker that enables lysosomal membrane receptors to recognize lysosomal enzymes. The transport of lysosomal enzymes across the lysosomal membrane is therefore defective. These and several other metabolic diseases are thus categorized as the disorders of the lysosomal enzyme transport. A genetic and biochemical heterogeneity, as well as clinical manifestations, are described in more detail.