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Biomedical subjects

A Bakkaloglu

Publications and source records attributed to A Bakkaloglu.

At least 55 records · Page 3Linked to original sources
PubMed1999

Localization of a gene for autosomal recessive distal renal tubular acidosis with normal hearing (rdRTA2) to 7q33-34.

Failure of distal nephrons to excrete excess acid results in the "distal renal tubular acidoses" (dRTA). Early childhood features of autosomal recessive dRTA include severe metabolic acidosis with inappropriately alkaline urine, poor growth, rickets, and renal calcification. Progressive bilateral sensorineural hearing loss (SNHL) is evident in approximately one-third of patients. We have recently identified mutations in ATP6B1, encoding the B-subunit of the collecting-duct apical proton pump, as a cause of recessive dRTA with SNHL. We now report the results of genetic analysis of 13 kindreds with recessive dRTA and normal hearing. Analysis of linkage and molecular examination of ATP6B1 indicated that mutation in ATP6B1 rarely, if ever, accounts for this phenotype, prompting a genomewide linkage search for loci underlying this trait. The results strongly supported linkage with locus heterogeneity to a segment of 7q33-34, yielding a maximum multipoint LOD score of 8.84 with 68% of kindreds linked. The LOD-3 support interval defines a 14-cM region flanked by D7S500 and D7S688. That 4 of these 13 kindreds do not support linkage to rdRTA2 and ATP6B1 implies the existence of at least one additional dRTA locus. These findings establish that genes causing recessive dRTA with normal and impaired hearing are different, and they identify, at 7q33-34, a new locus, rdRTA2, for recessive dRTA with normal hearing.

Acidosis, Renal Tubular↗
PubMed1998

Mutations in the chloride-bicarbonate exchanger gene AE1 cause autosomal dominant but not autosomal recessive distal renal tubular acidosis.

Primary distal renal tubular acidosis (dRTA) is characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. Kindreds showing either autosomal dominant or recessive transmission are described. Mutations in the chloride-bicarbonate exchanger AE1 have recently been reported in four autosomal dominant dRTA kindreds, three of these altering codon Arg589. We have screened 26 kindreds with primary dRTA for mutations in AE1. Inheritance was autosomal recessive in seventeen kindreds, autosomal dominant in one, and uncertain due to unknown parental phenotype or sporadic disease in eight kindreds. No mutations in AE1 were detected in any of the autosomal recessive kindreds, and analysis of linkage showed no evidence of linkage of recessive dRTA to AE1. In contrast, heterozygous mutations in AE1 were identified in the one known dominant dRTA kindred, in one sporadic case, and one kindred with two affected brothers. In the dominant kindred, the mutation Arg-589/Ser cosegregated with dRTA in the extended pedigree. An Arg-589/His mutation in the sporadic case proved to be a de novo mutation. In the third kindred, affected brothers both have an intragenic 13-bp duplication resulting in deletion of the last 11 amino acids of AE1. These mutations were not detected in 80 alleles from unrelated normal individuals. These findings underscore the key role of Arg-589 and the C terminus in normal AE1 function, and indicate that while mutations in AE1 cause autosomal dominant dRTA, defects in this gene are not responsible for recessive disease.

Acidosis, Renal Tubular↗
PubMed1998

Antineutrophil cytoplasmic antibodies in childhood systemic lupus erythematosus.

We aimed to evaluate the presence of peripheral antineutrophil cytoplasmic antibodies (p-ANCA) and cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) in children with SLE and to correlate its association of laboratory findings. Twenty-one children with SLE were studied. Serum samples in patients were tested by indirect immunofluorescence (IIF) slide kit (INOVA) for c-ANCA and p-ANCA and by ELISA for myeloperoxidase (MPO-ANCA) and proteinase 3 (PR3-ANCA). All the patients but two were quiescent for lupus at the time of sampling. Sixteen of 21 patients showed positive IIF staining whereas only 5 had MPO-ANCA and 2 of nine PR3-ANCA. The data suggests that SLE may be associated p-ANCA directed against additional target antigens rather than MPO and may be implicated in the pathogenesis of SLE or may be only non-specific antibodies developed in lupus.

Adolescent↗
PubMed1998

Prevalence of juvenile chronic arthritis and familial Mediterranean fever in Turkey: a field study.

OBJECTIVE: To investigate the prevalence of juvenile chronic arthritis (JCA), familial Mediterranean fever (FMF), and Behçet's disease in Turkish children through a field survey. METHODS: The field survey was based on cluster centering with 2 level strata. A total of 46,813 children were screened. For the diagnosis of chronic arthritis and Behçet's previously suggested criteria were used. We have developed criteria for the diagnosis of probable FMF. Children previously diagnosed to have these diseases were also defined and included. RESULTS: JCA was found in 6.4/10,000. 2.8/10,000 children were previously diagnosed as FMF (minimum phenotype frequency). Together with the probable diagnosis of FMF, the prevalence increased to 9.3/10,000. The findings were also compared with those of our center. None of the 46,813 children had Behçet's disease. CONCLUSION: The prevalence of chronic arthritis is similar to the other childhood populations reported. However, FMF has a very high prevalence.

Abdominal Pain↗
PubMed1997

Myelodysplastic features in juvenile rheumatoid arthritis.

We have attempted to investigate the dysplastic changes in the hematopoietic system associated with juvenile rheumatoid arthritis (JRA) and its relation to disease activity. The peripheral blood smear and bone marrow aspiration samples of 17 JRA patients were investigated and correlations with laboratory parameters of disease activity sought. The age range was 6-16 years and the duration of disease 1.5-108 months. Abnormal finding of the peripheral smear and bone marrow were scored separately. The score of pathological peripheral blood findings correlated significantly with CRP and ferritin (both P <0.05). In the bone marrow specimens marked changes were noted in the myeloid, erythropoietic, and megakaryopoietic series; however, the score of pathological findings did not correlate with laboratory parameters of disease activity (P > 0.05). We suggest that JRA is associated with marked myelodysplastic changes, also manifested in the peripheral blood smear; these changes may well be the consequence of the inflammatory milieu, including cytokines, during active disease.

Adolescent↗
PubMed1997

Interleukin-1, -6, and -8 levels in juvenile chronic arthritis.

The immunoinflammatory pathogenesis of juvenile chronic arthritis (JCA) involves the activation of many pathways including various cytokines. We have evaluated the levels of interleukin(IL)-1, IL-6 and IL-8 in 29 JCA patients. The age range was 1-16 with a mean of 10.1. A disease activity score was developed on the basis of: 1. constitutional symptoms and/or morning stiffness, 2. presence of joint swelling, 3.warmth, 4.limited range of motion, and 5.joint pain. This score correlated very significantly with laboratory disease activity markers such as erythrocyte sedimentation rate (ESR) and CRP (both p = 0.006) and also correlated with IL-1 and IL-6 levels. The levels of IL-1 decreased in four of the five patients with improved disease activity. IL-6 but not IL-1 correlated significantly with the number of inflamed joints (p = 0.013); IL-6 also strongly correlated with rheumatoid factor supporting this cytokine's role in B cell induction (p = 0). Haemoglobin values correlated negatively with the activity index, ESR, CRP, IL-1 and IL-6. IL-8 did not correlate with disease activity markers. In the systemic patients all cytokines tended to be higher. Our data suggest that interleukins 1 and 6 are effective in the pathogenesis of JCA. Whether cytokines may be used for monitoring therapy may be clarified with further studies.

Adolescent↗
PubMed1997

Development of systemic lupus erythematosus in a patient with selective complete C1q deficiency.

UNLABELLED: A 7-year-old male with recurrent erythematous and desquamated skin lesions and respiratory infections was diagnosed as selective complete C1q deficiency following detailed studies of the complement system. His asymptomatic sister also had selective complete C1q deficiency. During a follow up period of 3 years, his skin lesions persisted, he suffered from recurrent bronchopneumonias and glomerulonephritis developed. Renal function deteriorated with the appearance of anti-DNA antibodies. Renal biopsy was consistent with systemic lupus erythematosus. The patient was treated with immunosuppressive drugs, but died of renal failure. It is postulated that in this patient defective clearance of antigen-antibody complexes by the reticulo-endothelial system resulted in progressive renal disease as observed in other complement deficiencies. A retrospective molecular study disclosed a point mutation in the ClqA chain gene in a heterozygous state in parents and two siblings; in a homozygous state in the asymptomatic sister. The reason why some individuals with this defect are asymptomatic is not known at present. Diagnosis of heterozygotes by molecular studies is extremely important to give genetic counselling to the family. CONCLUSION: Patients with recurrent infections, erythematous desquamative skin lesions, malar rash and oral mucosal involvement should be screened for complement C1q deficiency.

Blood Protein Disorders↗
PubMed1997

Familial Mediterranean fever in children: report of a large series and discussion of the risk and prognostic factors of amyloidosis.

UNLABELLED: Familial Mediterranean fever (FMF) is a genetically transmitted disease characterized by recurrent attacks of fever and serositis. The most important complication of this disease is the development of amyloidosis. We present our analysis of 425 FMF patients without and 180 with amyloidosis (123 FMF having amyloidosis type 1 and 57 FMF having amyloidosis type II). The male female ratio was higher in the amyloidosis population (111/69) when compared to the FMF population (225 200) (P = 0.048). Consanguinity rate was the same among FMF and amyloidosis groups. However, a family history of amyloidosis was significantly more frequent in the amyloidosis group (P = 0.00001). Multivariate analysis has revealed that in FMF patients, the presence of a family history of amyloidosis plus consanguinity has a 6.04 fold increased risk of amyloidosis (P < 0.0001). The 5-year chronic renal failure free survival was 43.1% and 18.7% in type I and type II amyloidosis, respectively. The time interval to develop chronic renal failure after the development of amyloidosis was 4.8 in type I and 3.0 years in type II. respectively. We found ten cases of Henoch-Schönlein Purpura and nine of polyarteritis nodosa among our patients. The significance of the association between FMF and vasculitis awaits to be clarified. Among the FMF patients put on colchicine therapy (435), only 10 (2.3%) have developed amyloidosis confirming that this drug protects from amyloidosis. CONCLUSION: Since the presence of a familial history of amyloidosis has been defined as the most important risk factor in the development of amyloidosis, we suggest that additional genetic factors may be operative in the development of amyloidosis.

Amyloidosis↗
PubMed1997

Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III.

Analysis of patients with inherited hypokalaemic alkalosis resulting from salt-wasting has proved fertile ground for identification of essential elements of renal salt homeostasis and blood-pressure regulation. We now demonstrate linkage of this phenotype to a segment of chromosome 1 containing the gene encoding a renal chloride channel, CLCNKB. Examination of this gene reveals loss-of-function mutations that impair renal chloride reabsorption in the thick ascending limb of Henle's loop. Mutations in seventeen kindreds have been identified, and they include large deletions and nonsense and missense mutations. Some of the deletions are shown to have arisen by unequal crossing over between CLCNKB and the nearby related gene, CLCNKA. Patients who harbour CLCNKB mutations are characterized by hypokalaemic alkalosis with salt-wasting, low blood pressure, normal magnesium and hyper- or normocalciuria; they define a distinct subset of patients with Bartter's syndrome in whom nephrocalcinosis is absent. These findings demonstrate the critical role of CLCNKB in renal salt reabsorption and blood-pressure homeostasis, and demonstrate the potential role of specific CLCNKB antagonists as diuretic antihypertensive agents.

Bartter Syndrome↗
PubMed1997

Genetic linkage study of familial Mediterranean fever (FMF) to 16p13.3 and evidence for genetic heterogeneity in the Turkish population.

Familial Mediterranean fever (FMF) is an autosomal recessive condition that is almost entirely restricted to the non-Askhenazi Jews, Arabs, Armenians, and Turks. Genetic linkage study of a large group of non-Turkish families has previously mapped the FMF locus to the 16p13.3 region and shown that this locus resides 0.305 cM distal to D16S246. Furthermore, allelic association has also been shown with D16S3070 (75%) and D16S3275 (66%). However, no genetic heterogeneity has been described for any of the three major reported groups of FMF families. Here, we describe the genetic linkage relationship of the fourth major group of Turkish families and report the first evidence for genetic heterogeneity of this condition. Two point linkage analysis and haplotype inspection of 15 DNA markers from the reported region of the FMF locus identified tight linkage in a group of six Turkish FMF families. A maximum lod score of 9.115 at theta = 0.00 was observed for D16S3024. Nine other DNA markers provided similar evidence of linkage with lod score values of above 5.21. However, two other FMF families were completely unlinked to this region of chromosome 16. Haplotype construction of DNA markers in five consanguineous linked families showed that a segment of homozygosity has been conserved for D16S3070 and D16S2617. No other DNA markers showed any such conservation. Therefore, we suggested that these two markers reside in close proximity to the FMF locus. Furthermore, we observed 80% allelic association with D16S2617 but no association with D16S3070 or any other DNA markers from the FMF critical region. In summary, we conclude that our Turkish families are also linked to the reported FMF locus at 16p13.3, there is a genetic heterogeneity for this condition at least in our group of Turkish families, and D16S2617 is in linkage disequilibrium in the Turkish FMF families. Combination of this study with previously published observations suggests that the FMF locus resides between D16S246 and D16S3070/D16S2617 and within a region of about 250-300 kb.

Adolescent↗
PubMed1997

The role of cytokines in Henoch Schonlein purpura.

Serum levels of tumor necrosis factor (TNF) and interleukin(IL-1) were studied in 20 HSP patients, in the acute phase and after remission, by ELISA technique. Skin biopsies obtained during the acute phase both from a lesion and from unaffected skin, as well as during remission, were immunostained for TNF, IL-1, and IL-6. The mean age of the patients was 9.8 (5-13). Mean serum TNF levels during the acute phase and remission were 14.0 +/- 8.9 pg/ml, and 6.8 +/- 2.4 pg/ml, respectively (p < 0.05). Serum TNF levels in patients with renal involvement (18.8 +/- 10.2 pg/ml) were significantly higher than in those without (10.8 +/- 6.5 pg/ml) (p < 0.05). Serum levels of IL-1 in the acute phase and remission were undetectable. All specimens showed leukocytoclastic vasculitis. Immunohistochemical studies revealed TNF, and a less intense IL-1 and IL-6 staining in the nucleated epidermal layer, with a granular, intracellular pattern. Staining was significantly increased in the affected skin during the acute phase. These results suggest that TNF, IL-1, and IL-6 may play a role as a mediator of inflammation in HSP.

Adolescent↗
PubMed1996

Anaemia in juvenile chronic arthritis.

Anaemia is a common manifestation of juvenile rheumatoid arthritis (JCA). We have evaluated 26 JCA patients with anaemia and compared their laboratory parameters to those without anaemia. In the patients with anaemia, activation criteria such as erythrocyte sedimentation rate (ESR) and CRP were significantly higher than in those without anaemia. Anaemia was present in all systemic JCA patients and was present in 42% and 78% of the oligoarticular and polyarticular types, respectively. Serum iron levels and transferrin saturations were low in all, whereas serum iron-binding capacities of the patients were normal. Mean ferritin level was 249pg/l (range 8.46-1000pg/l). There was a significant correlation between ferritin levels and CRP and ESR (r = 0.48 and r = 0.55 respectively) (both p < 0.05). Epo levels were normal. Twelve (60%) of the bone marrow aspiration specimens stained positive for iron whereas 40% stained negative; there were also changes suggestive of myelodysplasia. Sideroblasts were also decreased in number. Thus, in these patients iron is not sufficiently transferred to the erythroid series and/or cannot be used by erythroblasts, accompanied by a possible absolute iron deficiency. Thus we suggest that the iron in JCA tends to be stored in the form of ferritin, not in an accessible form and impaired metabolism along with other factors are effective in the anaemia of JCA.

Adolescent↗
PubMed1996

Plasma lipids and lipoproteins in juvenile chronic arthritis.

Altered levels of high density lipoprotein (HDL), low density lipoprotein (LDL), and very-low density lipoprotein (VLDL), as well as apolipoproteins have been previously described in rheumatoid arthritis patients. We have attempted to evaluate the serum triglyceride, total cholesterol, cholesterol in DHL, LDL, apolipoprotein A1 (apo-A1) and apolipoprotein B (apo-B) levels in juvenile chronic arthritis (JCA) and to correlate them with CRP and ESR in the active and non-active stages of JCA. A total of 37 children no fulfilled ARA criteria for the diagnosis of JCA were studied. There were 18 girls and 19 boys. Age range was 2.5-16 years with a mean of 9.5. The mean duration of disease was 1.8 years. Nineteen patients were accepted to have active disease. Eighteen age and sex matched healthy children served as controls. Apo-A1 was significantly lower in the active JCA group when compared to inactive patients and healthy controls (both p < 0.05). There were significant inverse correlations between apo-A1 and both ESR and CRP levels in these patients (r = 0.67, p < 0.05 and r = -0.61, p < 0.-05, respectively). Although mean LDL levels were numerically lower in the JCA patients (67.2 mg/dl in the active and 68.6 mg/dl in the inactive patients) the difference with healthy controls (91.7 mg/dl) was not statistically significant. There was no significant differences in regard to triglyceride, total cholesterol, cholesterol in HDL, and apo-B levels between neither of the groups. We conclude that JCA patients have a dyslipoproteinaemic state with already altered metabolism of lipids at different stages of the chronic inflammation from active to inactive disease.

Adolescent↗