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1.
J Lamoril H Puy L Gouya R Rosipal V Da Silva B Grandchamp T Foint B Bader-Meunier JP Dommergues JC Deybach Y Nordmann 《Canadian Metallurgical Quarterly》1998,91(4):1453-1457
Porphyrias, a group of inborn errors of heme synthesis, are classified as hepatic or erythropoietic according to clinical data and the main site of expression of the specific enzymatic defect. Hereditary coproporphyria (HC) is an acute hepatic porphyria with autosomal dominant inheritance caused by deficient activity of coproporphyrinogen III oxidase (COX). Typical clinical manifestations of the disease are acute attacks of neurological dysfunction; skin photosensitivity may also be present. We report a variant form of HC characterized by a unifying syndrome in which hematologic disorders predominate: harderoporphyria. Harderoporphyric patients exhibit jaundice, severe chronic hemolytic anemia of early onset associated with hepatosplenomegaly, and skin photosensitivity. Neither abdominal pain nor neuropsychiatric symptoms are observed. COX activity is markedly decreased. In a first harderoporphyric family, with three affected siblings, a homozygous K404E mutation has been previously characterized. In the present study, molecular investigations in a second family with neonatal hemolytic anemia and harderoporphyria revealed two heterozygous point mutations in the COX gene. One allele bore the missense mutation K404E previously described. The second allele bore an A-->G transition at the third position of the donor splice site in intron 6. This new COX gene mutation resulted in exon 6 skipping and the absence of functional protein production. In contrast with other COX gene defects that produce the classical hepatic porphyria presentation, our data suggest that the K404E substitution (either in the homozygous or compound heterozygous state associated with a mutation leading to the absence of functional mRNA or protein) is responsible for the specific hematologic clinical manifestations of harderoporphyria. 相似文献
2.
H Rochant 《Canadian Metallurgical Quarterly》1997,45(7):579-586
Although the FAB classification of the myelodysplastic syndromes (MDS) allows to classify most patients, a few clinical patterns do not fit the FAB categories, including borderline forms with manifestations usually seen in other diseases and forms with atypical or unusual clinical or laboratory features that do not immediately suggest a MDS. Borderline forms are characterized by the presence of any of the following: high or very high platelet counts, myelofibrosis, bone marrow hypoplasia, eosinophilia, or systemic diseases such as relapsing polychondritis. Unusual or atypical forms include manifestations such as hemolysis, high reticulocyte counts, erythroblastopenia, or an abnormality of a single cell line such as isolated thrombocytopenia, isolated neutropenia, or isolated macrocytosis. The definitive diagnosis of these forms of MDS can require a number of investigations such as cytogenetic studies, bone marrow biopsy, and/or radionuclide evaluation, and may not be possible until the patient has been followed for some time. 相似文献
3.
The porphyrias, uncommon conditions often eluding diagnosis, extremely susceptible to inappropriate treatment and associated with severe late manifestations, are representative of the small groups of scarce and complex diseases that are difficult to manage without specialised resources. A network of offices with diagnostic and consultative support from a national specialist centre is probably the most cost effective way of meeting the patients' demands in terms of highly specialised medical experience coupled with close contact and continuity This approach, adopted by the Swedish Porphyria Centre, is based on well structured and regularly updated programmes for the management of porphyria patients. 相似文献
4.
RE Hammer 《Canadian Metallurgical Quarterly》1998,42(7):833-839
Bacterial lipopolysaccharide and a diverse array of other immunostimulants and cytokines suppress the metabolism of endogenous and exogenous substances by reducing the activity of hepatic cytochrome P-450 mixed function oxidase system. Although this effect of immunostimulants was first described almost 40 years ago, the mechanism is obscure. Immunostimulants are now known to cause nitric oxide overproduction by cells via induction of nitric oxide synthase. The highly reactive NO radical binds to prosthetic groups such as heme or iron-sulfur clusters leading to either activation or (more often) inhibition of iron-containing enzymes. It has been known for years that NO also binds to the heme moiety of cytochrome P-450 (CYP) with high affinity. However it was only recently demonstrated that binding of NO to CYPs also inhibits their enzymatic activity. This applies to both exogenously derived as well as endogenously synthesized NO. Suppression of CYP-dependent metabolism, which is a major problem of inflammatory liver diseases, can be significantly reversed by inhibition of NO synthesis in vivo under experimental conditions. The present paper reviews the findings implicating NO as a major factor mediating the suppression of CYP expression caused by endotoxins and immunostimulants in general. NO-mediated suppression of the metabolism of endogenous and exogenous substances under inflammatory conditions may contribute to the clinical manifestations and may be an important consideration for rational drug therapy in these conditions. 相似文献
5.
RE Iverson D Chelmow K Strohbehn L Waldman EG Evantash 《Canadian Metallurgical Quarterly》1996,88(3):415-419
Inheritance of idiopathic torsion dystonia (ITD) was studied in 41 Russian families including 41 probands with generalized, focal, and segmental dystonia and 140 recurred cases. Affected relatives appeared in two or more generations in 31 families analyzed. It was shown that in 76% of segregated cases, ITD was inherited as an autosomal dominant trait with a penetrance of 40% and varying expression. An autosomal recessive type was observed in 24% of the cases. Approximately 10% of the cases of disease could be caused by a new mutation and 14.6% by a nongenetic phenotype similar to genetic forms in its clinical symptoms. ITD with the X-linked recessive type of inheritance did not occur in the families studied. The recurrence risk was 20% in autosomal dominant forms. The risk correlated with age the relative's: clinical symptoms developed in 98.4% of patients by the age of 30. 相似文献
6.
H Yamaguchi M Nakazato M Miyazato K Kangawa S Matsukura 《Canadian Metallurgical Quarterly》1997,82(6):1934-1938
17alpha-Hydroxylase deficiency (17OHD) is an autosomal recessive disorder that produces an excess of mineralocorticoids and sexual differentiation abnormalities. Using DNA sequencing analysis of the 17alpha-hydroxylase (CYP17) gene from a Japanese patient with 17OHD, we identified a new type of genetic abnormality in this disease, a G to A transition at position +5 in the splice donor site of intron 7 of the CYP17 gene. In vitro expression analysis of an allelic minigene that consists of exons 6-8 of the patient's CYP17 gene showed that the transition causes the skipping of exon 7. This exon skipping alters the translational reading frame of exon 8 and introduces a premature stop codon (TAA) at amino acid position 410 proximal to the heme iron-binding site essential for the enzymatic activity of CYP17. Restriction enzyme analysis showed that the patient is homozygous for the mutated CYP17 gene, and the parents are heterozygotes. This is the first reported patient with 17OHD caused by the splice site mutation in the CYP17 gene. 相似文献
7.
AG Roberts H Puy TA Dailey RR Morgan SD Whatley HA Dailey P Martasek Y Nordmann JC Deybach GH Elder 《Canadian Metallurgical Quarterly》1998,7(12):1921-1925
Variegate porphyria (VP) is a low penetrance, autosomal dominant disorder that results from partial deficiency of protoporphyrinogen oxidase (PPOX) activity caused by mutation in the PPOX gene. The rare homozygous variant of VP is characterized by severe PPOX deficiency, onset of photosensitization by porphyrins in early childhood, skeletal abnormalities of the hand and, less constantly, short stature, mental retardation and convulsions. We have identified PPOX mutations on both alleles of five of the 11 unrelated patients with homozygous VP reported to date. Two patients were homoallelic for missense mutations (D349A and A433P), while three were heteroallelic. Functional analysis by prokaryotic expression showed that the D349A and A433P and one missense mutation in each of the three heteroallelic patients (G358R in two patients and A219KANA) preserved some PPOX activity (9.5-25% of wild-type). Mutations on the other allele of the heteroallelic patients abolished or markedly decreased activity. There was no relation between genotype assessed by functional analysis and the presence or severity of non-cutaneous manifestations. The mutations were absent from 104 unrelated patients with autosomal dominant VP. Our findings define the molecular pathology of homozygous VP and suggest that mild PPOX mutations occur in the general population but have very low or no clinical penetrance in heterozygotes. 相似文献
8.
BACKGROUND: The G6PD deficiency is a red cell enzymopathy very frequent in certain Mediterranean countries. In Menorca (Balearic Islands), a relatively high incidence of favism carried us to study the prevalence of this alteration, taking advantage of the "Campaign for detection of heterozygous beta-thalassaemia to prevent the homozygous beta-thalassaemia" that we make annually. METHODS: We studied a total of 1139 school boys between 13-14 years old for three consecutive school years. We used the methylene blue as screening test and the deficiency of G6PD was confirmed with enzymatic quantification in the haemolysate. We also analysed the clinical manifestations and studied the relatives. RESULTS: We have confirmed 11 cases of G6PD deficiency (prevalence of 9.7/1000), all of them native of the island. The clinical manifestations were: in 6 cases (54.5%) no clinical manifestations were found, 5 cases (45.4%) had presented neonatal jaundice and 2 cases (18.2%) had suffered a favism crisis. The study of relatives permitted us to analyse 26 additional samples (17 women and 9 men), detecting in 8 of them (4 women and 4 men) the enzymopathy . CONCLUSIONS: The prevalence of G6PD deficiency in Menorca is one of the highest in Spain. Most of the carriers are asymptomatic, the most important clinical manifestations being the neonatal jaundice and favism. The screening test used is efficient for unmistakable hemizygotes detection. 相似文献
9.
D Colville J Savige M Morfis J Ellis P Kerr J Agar R Fasset 《Canadian Metallurgical Quarterly》1997,18(3):119-128
Ocular abnormalities are common in X-linked Alport syndrome, but they have not been studied in patients with the rarer autosomal recessive disease. We have examined the eyes of a family with autosomal recessive Alport syndrome. Four of the eight offspring of a consanguineous marriage had renal failure and deafness by the age of 20 years. The diagnosis of Alport syndrome was confirmed on the ultrastructural demonstration of a lamellated glomerular basement membrane (GBM) in one affected family member. Autosomal recessive inheritance was suggested by the lack of linkage to the COL4A5/COL4A6 locus, and by linkage to the COL4A3/COL4A4 locus. All four affected family members had anterior lenticonus (or had had a lens replacement for this) and the three who were examined had a dot-and-fleck retinopathy. Neither of the two unaffected offspring who were examined nor the father had these abnormalities. The ocular manifestations of autosomal recessive Alport syndrome are probably identical to those for the X-linked form. Although the mutations in these diseases affect genes for different type IV collagen chains, these chains occur together in the basement membranes of the kidney, eye and ear, and abnormalities in any one may result in the same clinical phenotype. 相似文献
10.
NS Kisliak RV Lenskaia EIu Shvedova GV Kolenkova KL Kondratchik NA Finogenova EA Mamedova AM Akk IaIa Lutskaia EN Dolgina AA Afanas''eva LKh Pronina 《Canadian Metallurgical Quarterly》1996,41(2):7-10
The present study concerns 63 patients with autosomal polycystic kidney disease. In 35 patients the disease was linked to chromosome 16, and in the remaining 28 it was not linked to this chromosome. A comparative clinical analysis of the clinical manifestations of each of the forms was carried out using the objective criteria of age at onset of the initial clinical manifestations of ADPKD, age at onset of the hypertension syndrome, age at onset of the initial chronic renal failure and beginning of haemodialysis. The results show that the clinical manifestations of ADPKD in the patients with the unlinked from are milder and with a better prognosis. 相似文献
11.
M Ragno G De Michele F Cavalcanti L Pianese A Monticelli L Curatola F Bollettini S Cocozza G Caruso L Santoro A Filla 《Canadian Metallurgical Quarterly》1997,49(6):1617-1620
We describe three siblings from an Italian family affected by an autosomal recessive spinocerebellar degeneration. Gait ataxia, presenting between 38 and 45 years, was the first symptom in all three patients. Dysarthria, dysmetria, brisk tendon reflexes, extensor plantar response, and scoliosis were constant features. Disease progression was slow. Electrophysiologic studies demonstrated a slight reduction in sural nerve sensory action potential in only one patient. Analysis of GAA expansion within the X25 gene showed that patients were homozygous for the expansion, with the shorter expanded allele ranging from 120 to 156 triplets. The size of the GAA expansion may be smaller than we previously described. Such minimal expansions may result in atypical forms of Friedreich's ataxia. 相似文献
12.
Y Horie J Okano S Kitaoka F Tajima H Kawasaki 《Canadian Metallurgical Quarterly》1995,53(6):1456-1462
There are seven porphyrias which are caused by defective functions of the enzymes in the haem biosynthesis. The clinical classification of porphyrias are divided into three types which are neuroporphyria, neurocutaneous porphyria and cutaneous porphyria. For acute porphyric attack of neuroporphyria and neurocutaneous porphyria, the treatments of choice are administration of glucose and/or hematin, haem arginate and tinprotoporphyrin. Porphyria cutanea tarda in cutaneous porphyria is controlled by removal of iron by phrebotomies or low-dose chloriquine. A novel approach of intravenous administration of interferon may be useful to control the associated case of chronic hepatitis type C. Skin symptoms in erythropoietic protoporphyria can be alleviated with beta carotene. Hepatic failure due to protoporphyria may need a liver transplantation. Cimetidine, a H2-receptor antagonist, may be useful in the treatment of acute porphyric attack and in remission stage in neuroporphyrias, neurocutaneous porphyrias and cutaneous porphyrias such as porphyria cutanea tarda and protoporphyria. 相似文献
13.
We studied the clinical and biochemical manifestations of complete adenine phosphoribosyltransferase deficiency in the kindred of a male homozygous child excreting stones of 2,8-dihydroxyade-nine. Abnormal amounts of adenine, 8-hydroxyade-nine and 2,8-dihydroxyadenine (25 per cent of total purine metabolites) appeared in the urine of the propositus and his clinically normal brother, but not in heterozygotes or a control. Adenine phosphoribosyl-transferase activity in erythrocytes was less than 1 per cent of normal in both homozygotes and varied from 20 to 57 per cent of normal in six heterozygotes. Heterozygotes exhibited neither hyperuricemia nor gout. Treatment of the propositus with allopurinol and a low purine diet stopped stone formation. In addition, excretion of 2,8-dihydroxyadenine decreased. An autosomal recessive mode of inheritance with variable expression in the phenotype is indicated. Homozygotes may be detected by their raised urinary adenine levels or absence of detectable erythrocyte adenine phosphoribosyltransferase activity (or both). 相似文献
14.
Endometriotic deposits are not uncommon in the large bowel of women. Because the symptoms produced by endometriosis may lead to investigation by colorectal endoscopic biopsy, the aims of this study were to assess the range of mucosal abnormalities that may occur and to determine whether this could represent a significant potential diagnostic problem. We found mucosal changes in eight of 10 cases of colorectal endometriosis; however, the abnormalities (ulceration, gland architectural disturbance, crypt abscess formation, increased inflammatory cell presence, and smooth muscle fibers between glands in the mucosa) were focal and directly related to endometrial deposits. In one case an abnormal colonic biopsy specimen from a patient with endometriosis supported the erroneous clinical diagnosis of Crohn's disease. Comparing a group of women with endometriosis to a group with adenomyosis of the uterus showed that although more women with endometriosis have endoscopic large bowel biopsies, there was no significant excess of biopsy specimens showing inflammatory changes. Our conclusion is that the endometriosis of the large bowel can masquerade as inflammatory bowel disease or ischemic changes and the possibility should be borne in mind, particularly in cases with atypical clinical features or very focal histological changes. 相似文献
15.
MH Bosnar K Paveli? S Krizanac Z Slobodnjak J Paveli? 《Canadian Metallurgical Quarterly》1997,75(8):609-613
The position of the jugular bulb varies greatly. A high jugular bulb procident from the temporal bone is not uncommon. Most people with this anatomic variation remain asymptomatic. We report seven cases of high jugular bulb with clinical manifestations. The anatomy, clinical manifestations, diagnosis, and management are reviewed. 相似文献
16.
Y Pirson 《Canadian Metallurgical Quarterly》1996,151(10-11):447-52; discussion 452-3
Alport syndrome is a hereditary nephropathy, inconstantly associated with sensorineural deafness and ocular abnormalities. These manifestations result from a structural defect in type IV collagen. Recent genetic advances have provided a molecular basis for the two main subsets of the disease, namely the X-linked and the autosomal recessive forms. It has just been shown that the autosomal dominant entity known as benign familial haematuria is actually due to a heterozygote mutation of the gene accounting for the autosomal recessive form of Alport syndrome. The genetic breakthrough has already clinical and pathophysiological implications. 相似文献
17.
We describe a patient with a 19-year history of lymphocytic lung infiltrations. A diagnosis of lymphocytic interstitial pneumonitis was made in 1982 after an open lung biopsy, but in 1995 a comprehensive re-evaluation led to the diagnosis of Waldenstr?m's macroglobulinaemia with primary bronchopulmonary involvement. It could also be demonstrated by polymerase chain reaction and immunological techniques that this disease had been present since before 1982. In 1995 it was still difficult to demonstrate bone marrow involvement, even with new and sensitive methods. We discuss some diagnostic problems of organ manifestations of uncommon systemic diseases. Pulmonary manifestations of Waldenstr?m's macroglobulinaemia or other diseases of the immune system should be considered in patients with atypical lung disorders. 相似文献
18.
MR Baumgartner BT Poll-The NM Verhoeven C Jakobs M Espeel F Roels D Rabier T Levade MO Rolland M Martinez RJ Wanders JM Saudubray 《Canadian Metallurgical Quarterly》1998,44(5):720-730
To illustrate the clinical and biochemical heterogeneity of peroxisomal disorders, we report our experience with 27 patients seen personally between 1982 and 1997. Twenty patients presented with a phenotype corresponding either to Zellweger syndrome, neonatal adrenoleukodystrophy, or infantile Refsum disease, 3 of whom had a peroxisomal disorder due to a single enzyme defect. One patient had a mild form of rhizomelic chondrodysplasia punctata, 1 had classic Refsum disease. Finally, 5 patients presented with clinical manifestations that were either unusually mild or completely atypical, and initially did not arouse suspicion of a peroxisomal disorder. They showed multiple defects of peroxisomal functions with one or several functions remaining intact, suggesting a peroxisome biogenesis disorder. The defect in peroxisome biogenesis was further characterized by variable expression in different tissues and/or individual cells in 5 patients. Studies restricted to fibroblasts failed to identify abnormalities in this group. We demonstrate that clinical manifestations of peroxisomal disorders may be very mild or completely atypical, and therefore, peroxisomal disorders should be considered in a variety of clinical settings. Furthermore, we suggest performing extensive peroxisomal investigations in every patient suspected of suffering from a peroxisomal disorder, even when the clinical presentation is typical. 相似文献
19.
Cutaneous disorders occur with great frequency in patients with HIV infection and increase in number and severity as the disease progresses and immune function declines. In addition, the first findings related to HIV infection are often on the skin. Cutaneous infections with herpesviruses may be severe and atypical in their presentations; papillomaviruses and MC are common as well. Bacterial infections may be primary or secondary to other skin diseases; superficial and deep fungal infections are also prevalent. Papulosquamous disorders, including seborrheic dermatitis, psoriasis, and eczema, may be disfiguring and result in secondary complications. Neoplastic disorders, especially Kaposi's sarcoma, demand early diagnosis, to afford the patient maximal treatment options. All physicians must be aware of these cutaneous manifestations to decrease morbidity and improve quality of life in the HIV-infected individual. 相似文献
20.
Y Jammes S Delpierre MJ Delvolgo C Humbert-Téna H Burnet 《Canadian Metallurgical Quarterly》1998,53(6):372-377
Hepatitis C virus infection and rheumatic disorders are both common in the Middle East and share many clinical and immunological manifestations, raising diagnostic problems. We compared the prevalence of extrahepatic clinical manifestations and immunological disorders in 40 patients with chronic hepatitis C and in 42 carefully matched healthy controls. Polyarthralgia or polyarthritis was the most common rheumatic manifestation (35%) in the cases, followed by cutaneous vasculitis (15%). Glomerulonephritis and xerophthalmia were uncommon, and none of the cases had systemic vasculitis. Immunological abnormalities included serum rheumatoid factor (47.5%), cryoglobulins (30%), and one or more antitissue antibodies (37.5%). The prevalences of polyarthralgia, cutaneous vasculitis, rheumatoid factor, cryoglobulinemia, and anti-tissue antibodies were significantly higher in the hepatitis C group than in the control group. Our data suggest that patients in the Middle East who present with features of rheumatic or autoimmune diseases should be screened for hepatitis C. 相似文献