Follow-up of patients with juvenile nephronophthisis after renal transplantation: a single center experience.

BACKGROUND: Nephronophthisis (NPHP) is the most common genetic cause of end-stage renal disease (ESRD) in the first 3 decades of life. Treatment of patients with NPHP is symptomatic; kidney transplantation is the treatment of choice when ESRD is established. We report herein our center's experience with kidney transplantation for children with juvenile NPHP. PATIENTS: We retrospectively analyzed medical records of 9 renal transplant recipients with a primary diagnosis of juvenile NPHP confirmed by genetic analysis and/or renal biopsy findings in a single center from 1996 to 2010. RESULTS: Of the 9 patients, 6 received a living related and 3 a cadaveric donor transplantation. Preemptive renal transplantation was performed in 7 patients. The median age of the patients was 13.38 ± 4.6 years; the median follow-up period was 17 months. Posttransplantation immusuppression comprised corticosteroids, a calcineurin inhibitor, and mycophenolate mofetil or azathioprine. One patient lost his renal graft owing to renal graft thrombosis, and grade II chronic allograft nephropathy was diagnosed by renal biopsy on the 62th day after renal transplantation in another patient. The median glomerular filtration rates after transplantation at 1, 3, and 5 years were 85, 75.2, and 83.2 mL/min/1.73 m(2), respectively. CONCLUSION: We observed preserved graft functions for long periods among renal transplant recipients with juvenile NPHP. Chronic allograft nephropathy developed rarely on long follow-up.

Henoch-Schönlein nephritis: a nationwide study.

BACKGROUND/AIM: The aim of this retrospective study was to evaluate the presentation, clinical and pathological manifestations and outcome of the Henoch-Schönlein purpura (HSP) nephritis in children. METHODS: Clinical and laboratory data of 443 children with HSP nephritis aged between 3 and 16 years from 16 pediatric nephrology reference centers were analyzed retrospectively. The biopsy findings were graded according to the classification developed by the International Study of Kidney Disease in Children (ISKDC). RESULTS: Renal biopsy was performed in 179 of the patients with HSP nephritis. The most common presenting clinical finding in patients who were biopsied was nephrotic range proteinuria (25%) which was followed by nephritic-nephrotic syndrome (23.5%). The biopsy findings according to the ISKDC were as follows: class I: 8.3%; II: 44.1%; III: 36.3%; IV: 6.7%; V: 3.3%; VI: 1.1%. All of the patients who developed end-stage renal disease had nephritic-nephrotic syndrome at presentation. Of 443 patients, 87.2% had a favorable outcome and 12.8% had an unfavorable outcome. The overall percentage of children who developed end-stage renal disease at follow-up was 1.1%. Logistic regression analysis did not show any association of initial symptoms and histology with outcome. CONCLUSION: In the presented cohort, the presence of crescents in the first biopsy or presenting clinical findings did not seem to predict the outcome of HSP nephritis in children. We conclude that children with HSP nephritis even with isolated microscopic hematuria and/or mild proteinuria should be followed closely.

MEFV mutations in systemic onset juvenile idiopathic arthritis.

OBJECTIVES: Autoinflammatory diseases constitute a large spectrum of monogenic diseases like FMF or cryopyrin-associated periodic syndromes (CAPS) and complex genetic trait diseases such as systemic onset juvenile idiopathic arthritis (SoJIA). An increased rate of MEFV mutations has been shown among patients with PAN and HSP, in populations where FMF is frequent. The aim of the study is to search for MEFV mutations in our patients with SoJIA and see whether these mutations had an effect on disease course or complications. METHODS: Thirty-five children with the diagnosis of SoJIA were screened for 12 MEFV mutations. The control data were obtained from a previous study of our centre determining the carrier frequency in Turkish population. RESULTS: Two patients were homozygous and three patients were heterozygous for the M694V mutation. One patient was a compound heterozygote for the M680I/V726A mutations. Heterozygous V726A mutation was found in one patient. The overall mutation frequency of patients was 14.28%. This figure had been compared with the previously published rate of disease-causing mutations in this country, which is 5%. Disease-causing mutations were found to be significantly more frequent in the SoJIA patients than the population (P < 0.01). Among these, M694V was the leading mutation with a frequency of 10% in SoJIA. Six patients carrying MEFV mutations were among the most resistant cases requiring biological therapy. CONCLUSION: SoJIA patients had a significantly higher frequency of MEFV mutations but clinical studies with large number of patients are needed to confirm the association of MEFV mutations with SoJIA and its course.

Disease severity in children and adolescents with familial Mediterranean fever: a comparative study to explore environmental effects on a monogenic disease.

BACKGROUND: Worldwide, familial Mediterranean fever (FMF) is the most common autoinflammatory disease. It has been suggested that environmental factors affect the phenotype as some patients do not develop the complication of secondary amyloidosis. OBJECTIVE: To analyse whether disease severity in Turkish children with FMF, living in Turkey and Germany is different. PATIENTS AND METHODS: A total of 55 Turkish children living in Turkey were compared with 45 Turkish children born and raised in Germany. Mean age among the group from Turkey and Germany was 42.2 and 44.29 months, respectively. M694V was the leading mutation in both groups. The severity scores were compared with two scoring systems, modified according to published paediatric data for dosage. RESULTS: There was no significant difference between the mean C-reactive protein and erythrocyte sedimentation rate levels of the two groups. According to the modified Sheba Center score, 78.2% of patients from the group living in Turkey had a severe course compared with 34.1% from the group living in Germany. The modified score of Pras et al also showed more severe disease in the patients from Turkey. The difference between the two groups for both scoring systems were significant (both p<0.05). CONCLUSIONS: We believe the modified scores that we introduce can be widely used for children. Our results suggest that the environment affects the phenotype of a monogenic disease of the innate inflammatory pathway.

The analysis of interleukin-1 receptor antagonist and interleukin-1beta gene polymorphisms in Turkish FMF patients: do they predispose to secondary amyloidosis?

OBJECTIVE: Amyloid development in familial Mediterranean fever (FMF) patients is associated with acute phase response and the acute phase reactant serum amyloid A which is induced by IL-1Beta. Its concentration can increase to more than 1000 fold during inflammation. In view of the inflammatory nature of FMF disease we have investigated whether IL-1Beta and IL-1 receptor antagonist gene polymorphisms may be involved in amyloid development in FMF patients. METHODS: Ninety-nine FMF patients without amyloidosis; 54 FMF patients with amyloidosis and 60 healthy controls samples were genotyped for IL-1Beta-511 (C/T) and IL-1Beta+3953 (C/T) polymorphisms using PCR-RFLP and for IL-1Ra VNTR polymorphism using PCR. RESULTS: The allele and genotype frequencies of IL-1Beta-511 (C/T), IL-1Beta+3953 (C/T) and IL-1Ra VNTR polymorphisms in FMF patients with and without amyloidosis were all compared with those in controls. There were no significant differences between FMF patients with and without amyloidosis and healthy control samples for these polymorphisms (all P-values are >0.05). These polymorphisms were not associated with M694V mutation in FMF patients with and without amyloidosis. CONCLUSION: IL-1Beta-511 (C/T), IL-1Beta+3953 (C/T) and IL-1Ra VNTR polymorphisms are not associated with the development of amyloid in FMF patients.

Preoperative evaluation of hilar vessel anatomy with 3-D computerized tomography in living kidney donors.

OBJECTIVES: Digital subtract angiography is the gold standard for anatomic assessment of renal vasculature for living renal donors. However, multidetector-row computerized tomography (MDCT) is less invasive than digital subtract angiography and provides information of kidney stones and other intra-abdominal organs. In this study, preoperative MDCT angiography results were compared with the peroperative findings to evaluate the accuracy of MDCT for the evaluation of renal anatomy. METHODS: From December 2002 to May 2007, all 60 consecutive living kidney donors were evaluated with MDCT angiography preoperatively. We reported the number and origin of renal arteries, presence of early branching arteries, and any intrinsic renal artery disease. Renal venous anatomy was evaluated for the presence of accessory, retroaortic, and circumaortic veins using venous phase axial images. The calyces and ureters were assessed with delayed topograms. The results of the MDCT angiography were compared with the peroperative findings. RESULTS: A total of 67 renal arteries were seen peroperatively in 60 renal units. Preoperative MDCT angiography detected 64 of them. The two arteries not detected by MDCT had diameters less than 3 mm. Anatomic variations were present in nine veins, five of which were detected by CT angiography. Sensitivity of MDCT angiography for arteries and veins was 95% and 93%, respectively. Positive predictive values were 100% for both arteries and veins. CONCLUSION: MDCT angiography offers a less invasive, rapid, and accurate preoperative investigation modality for vascular anatomy in living kidney donors. It also provides sufficient information about extrarenal anatomy important for donor surgery.

Renal transplantation in children with lower urinary tract dysfunction of different origin: a single-center experience.

INTRODUCTION: Renal transplantation in patients with lower urinary tract dysfunction (LUTD) of various origins is a challenging issue in the field of pediatric transplantation. We report our single-center experience to evaluate patient and graft survivals as well as the risks of the surgery and immunosuppressive therapy. PATIENTS AND METHODS: Among 70 pediatric transplant patients, 11 displayed severe LUTD. Videourodynamic tests were performed on all patients preoperatively as well as postoperatively if required. The cause of urologic disorders were neurogenic bladder (n = 5) and urethral valves (n = 6). Clean intermittent catheterization (CIC) was needed in six patients to empty the bladder. To achieve a low-pressure reservoir with adequate capacity pretransplantation augmentation ileocystoplasty was created in four patients and gastrocystoplasty in one patient. Three of the patients received kidneys from cadaveric and eight from living donors. All patients were treated with calcineurin-based immunosuppressive therapy. RESULTS: The mean age at transplantation was 15 +/- 4.7 years. The median follow-up after transplantation was 36 months (6 to 62 months). At their last visit the median creatinine level was 0.95 mg/dL (0.8 to 2.4 mg/dL). Three patients had recurrent symptomatic urinary tract infections who had augmented bladder on CIC. One patient with ileocystoplasty who developed urinary leak and ureteral stricture in the early postoperative period was treated by an antegrade J stent. CONCLUSION: Severe LUTD carried high risks for the grafted kidney. However, our data suggested that renal transplantation is a safe and effective treatment modality, if the underlying urologic diseases properly managed during the transplantation course. Since surgery and follow-up is more complicated, patient compliance and experience of transplantation team have significant impacts on outcomes.

Outcome of primary glomerular disease in pediatric renal transplantation: a single-center experience.

INTRODUCTION: The recurrence of primary disease in transplantation is a well-known problem. We report our single-center experience to assess the frequency of the recurrence of primary glomerulonephritis in children after renal transplantation. PATIENTS AND METHODS: Medical reports of 14 children with primary glomerular disease were evaluated. Among the 14 grafts were 10 from living related and four from cadaveric donors. Ten were diagnosed as focal segmental glomerulosclerosis (FSGS), two membranoproliferative glomerulonephritis (MPGN), and two polyarteritis nodosa (PAN). The original diagnosis was biopsy-proven in every case. All patients were treated with calcineurin-based immunosuppressive therapy. RESULTS: The mean age was 15.5 +/- 5.4 years. The median transplantation duration was 47 months; however, one of the FSGS patient had hyperacute rejection. Five years later she received a second graft with a serum creatinine of 0.7 mg/dL at 7 years after transplantation. Posttransplant recurrence of FSGS was confirmed in two patients (20%), who were treated with plasmapheresis with no improvement of proteinuria, two FSGS patients had thromboses after transplantation. One had a cardiac thrombosis with heterozygote MTHFR mutation and one, a renal artery thrombosis and loss of graft with prothrombin 20210A mutation. They all have functioning grafts except these two. We did not observe recurrence of PAN or MPGN in patients. CONCLUSION: Although the number of patients is quite small, our recurrence rate was compatible with the previous reports. Additionally, we strongly recommend evaluation of all risk factors for thrombosis and give appropriate anticoagulation.

Triple immunosuppression with tacrolimus in pediatric renal transplantation: single-center experience.

AIM: In this single-center cohort, we retrospectively analyzed the efficacy and safety of tacrolimus in pediatric renal transplantation. METHODS: We examined the medical records of 22 consecutive renal transplantation recipients (12 boys, 10 girls) receiving tacrolimus, to evaluate occurrence of acute rejection (AR) episodes, glomerular filtration rates (GFR), and side effects. RESULTS: The mean recipient age was 15.07 +/- 3.96 years. Seven grafts came from cadaveric, and 15 from living related donors. The patients were placed on immunosuppression with prednisolone and tacrolimus plus azathioprine (n = 8) or mycophenolate mofetil (MMF) (n = 12) or enteric-coated mycophenolate sodium (n = 2). Eighteen patients received basiliximab on days 0 and 4. There were three AR episodes at 5, 9, and 12 months. Mean GFR at the end of 1 and 2 years were 97.1 +/- 24.0 mL/min/1.73 m(2) and 116.9 +/- 42.2 mL/min/1.73 m(2), respectively. There was no graft loss. Hypertension, hyperlipidemia, and hyperglycemia were present in 14 (63.6%), 3 (13.6%), and 3 (13.6%) patients, respectively, without gingival hyperplasia, tremor, or hypertrichosis. Supraventricular tachycardia was noticed in five patients (22.7%), three of whom needed antiarrhythmic drugs (13.6%). CONCLUSION: Our single-center experience with tacrolimus, steroid plus azathioprine or MMF or enteric-coated mycophenolate sodium regimen in pediatric kidney recipients showed a low rate of AR with excellent graft survival and function at 1 and 2 year posttransplantation. The increased rate of supraventricular tachycardia in this regimen had not been previously reported; this association merits further studies.

Interferon-gamma assays for the diagnosis of tuberculosis infection before using tumour necrosis factor-alpha blockers.

OBJECTIVES: Patients who receive tumour necrosis factor-alpha (TNF-alpha) blockers are mostly immunosuppressed. A study was performed to investigate whether an interferon-gamma (IFN-gamma) assay could represent an alternative approach to the tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection (LTBI) in these patients. DESIGN: We prospectively enrolled 106 individuals into the study in two groups. Group 1 consisted of 38 healthy individuals and Group 2 included 68 patients with chronic inflammatory diseases evaluated for LTBI before the use of TNF-alpha blockers. RESULTS: Of all participants, nine had indeterminate IFN-gamma test results. Agreement between the two tests was poor in both groups (kappa values respectively -0.54 and 0.18). In a total of 97 subjects, 10 (10.3%) were positive by the IFN-gamma test and 49 (50.5%) by TST. CONCLUSION: We found poor agreement between TST and the IFN-gamma test in our study. Our limited preliminary data should be accepted as a basis for designing future studies that will be helpful for physicians to decide whether the IFN-gamma test is more sensitive than the TST test in detecting LTBI before the use of TNF-alpha blockers.

Are carriers for MEFV mutations "healthy"?

OBJECTIVE: We aimed to compare whether carriers for the MEFV mutations display an increase or decrease in certain features. We compared the frequency of a number of inflammatory symptoms and diseases in carriers and a control population. METHODS: A questionnaire was designed to be applied to parents of children with FMF and a control group of parents. Clinical features and some diseases including the frequency of febrile episodes, abdominal pain, arthralgia, prophylaxis with penicillin, acute rheumatic fever, rheumatoid arthritis, vasculitis, spondyloarthropathy, urinary tract infection, asthma, allergy, irritable bowel disease, appendectomy and tonsillectomy were inquired. 676 parents of 440 children with FMF were surveyed in this study. Controls (n: 774) were selected as parents of healthy children. RESULTS: The presence of febrile episodes more than four per year, arthralgia, past diagnosis for acute rheumatic fever, rheumatoid arthritis and prophylaxis of penicillin, acute rheumatic fever, and rheumatoid arthritis were significantly higher in asymptomatic parents for the MEFV mutations compared to controls. The frequency of allergy was found to be significantly lower in the asymptomatic parents as compared to controls. There was no significant difference at the frequency of urinary tract infection and tonsillectomy between the parents of the patents and controls. CONCLUSIONS: We suggest that one MEFV mutation may indeed be conferring a heightened inflammation as suggested by the increased frequency in inflammatory symptoms. The carrier status for MEFV mutations seem to be unique, in that they cause an alteration in the state of "health".

Recessive missense mutations in LAMB2 expand the clinical spectrum of LAMB2-associated disorders.

Congenital nephrotic syndrome is clinically and genetically heterogeneous. The majority of cases can be attributed to mutations in the genes NPHS1, NPHS2, and WT1. By homozygosity mapping in a consanguineous family with isolated congenital nephrotic syndrome, we identified a potential candidate region on chromosome 3p. The LAMB2 gene, which was recently reported as mutated in Pierson syndrome (microcoria-congenital nephrosis syndrome; OMIM #609049), was located in the linkage interval. Sequencing of all coding exons of LAMB2 revealed a novel homozygous missense mutation (R246Q) in both affected children. A different mutation at this codon (R246W), which is highly conserved through evolution, has recently been reported as causing Pierson syndrome. Subsequent LAMB2 mutational screening in six additional families with congenital nephrotic syndrome revealed compound heterozygosity for two novel missense mutations in one family with additional nonspecific ocular anomalies. These findings demonstrate that the spectrum of LAMB2-associated disorders is broader than previously anticipated and includes congenital nephrotic syndrome without eye anomalies or with minor ocular changes different from those observed in Pierson syndrome. This phenotypic variability likely reflects specific genotypes. We conclude that mutational analysis in LAMB2 should be considered in congenital nephrotic syndrome, if no mutations are found in NPHS1, NPHS2, or WT1.

Semen variables and hormone profiles after kidney transplantation during adolescence.

Our aim was to investigate the semen variables and hormone profiles among transplant patients who received kidneys during adolescence. Seven postpubertal transplant patients who underwent successful renal transplantation during adolescence (13-19 years; 3 were preemptive) were enrolled in our clinical follow-up. Serum levels of prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were checked together with the semen analysis. The ages of the patients ranged from 18 to 25 years (median, 22 years). The median age was 15 years (range, 12-18 years) at initial presentation. The median time between initial diagnosis and transplantation was 12 months (range, 2-60 months). The median follow-up after transplantation was 51 months (range, 23-134 months). Three of the seven patients had unilateral low testicular volume. The renal function tests were within normal limits, as well as serum levels of prolactin, FSH, LH, and testosterone. Sperm counts ranged from 0.2 to 55 million/mL (median, 1.7 million/mL). Only 1 patient (14.2%) had normal sperm parameters. Oligoteratozoospermia (low sperm count and defects in morphology) was observed in 1/7 (14.2%), asthenoteratozoospermia (low levels of motility and defects in morphology) in 1/7 (14.2%), and all parameters were abnormal in 4/7 (57.1%) cases. Our data suggest that in contrast to adult patients, semen variables are severely affected and spermatogenesis does not improve after renal transplantation when the patient was subjected to uremia before or during adolescence, the crucial period for spermatogenesis.

How does the presence of urologic problems change the outcome of kidney transplantation in the pediatric age group.

PURPOSE: We retrospectively reviewed the impact of functional and anatomic urologic disorders on kidney transplantation outcomes in terms of the surgical and long-term results of pediatric renal transplantation. MATERIALS AND METHODS: Of the 55 kidney transplantations in the pediatric age group, end-stage renal disease (ESRD) was secondary to genitourinary disorders in 23 patients (42%). The urologic abnormalities were vesicoureteral reflux in 13 patients (59%), neurogenic bladder in 4 patients (18%), posterior urethral valves in 3 patients (14%), renal stone disease in 4 patients (18%), bilateral ureterovesical junction obstruction in 3 patients (14%), and unilateral renal agenesis with concomitant contralateral ureteropelvic junction obstruction in 1 patient (4%). RESULTS: Of the 23 patients with urologic problems, 19 (83%) had functioning grafts with a mean follow-up of 49 months (range, 7-120 months). In the other 32 patients, 26 (81%) had functioning grafts with a mean follow-up of 43 months (range, 1-144 months). The graft survival, mean serum creatinine, and urinary tract infection rates of the patients did not differ between the two groups. CONCLUSIONS: The presence of functional urologic disorders as the cause of ESRD did not seem to change the outcome of renal transplantation in terms of graft survival when compared with patients without any urologic disorders. Urinary tract infections seem to be a little more common and yet clinically not significant in those patients. Reflux does not always need to be corrected before transplantation, unless it is causing symptoms or infection.

Renal transplantation in children with augmentation enterocystoplasty.

INTRODUCTION: We report our experience with renal transplantation in patients with severe bladder dysfunction who underwent prior augmentation cystoplasty. PATIENTS AND METHODS: Among 58 pediatric patients, three underwent bladder augmentation prior to renal transplantation. The patients' ages at transplantation were 10, 13, and 17. The etiologies of bladder dysfunction were posterior urethral valves in two patients and contracted bladder in one patient. Vesicoureteral reflux was concomitantly present in three patients. Pretransplant ileocystoplasty was created in two patients and gastrocystoplasty in one patient. All patients received kidneys from cadaveric donors and were treated with calcineurin-based immunosuppressive therapy. RESULTS: The patients had normal renal function without hydronephrosis of the transplanted kidney at 13, 22, 49 months follow-up. No patients had morbidity due to technical complications. All the patients were continent. Two of three patients required clean intermittent catheterization from a Mitrofanoff conduit, while one patient spontaneously voids without significant residual urine. Urinary tract infections observed in two patients were successfully treated without any permanent deterioration in graft kidney function. CONCLUSIONS: Our data suggest that augmentation cystoplasty is a safe and effective option to treat patients with end-stage renal disease undergoing kidney transplantation. Experience of the transplantation team with a qualified pediatric urologist is essential due to the potentially high risk of surgical complications during the long term management of these patients.

E148Q is a disease-causing MEFV mutation: a phenotypic evaluation in patients with familial Mediterranean fever.

BACKGROUND: Familial Mediterranean fever (FMF) is one of the periodic fever syndromes. It is common among Turks, Jews, Arabs, and Armenians. Several mutations in the MEFV gene, including E148Q, have been identified as causing this disease. It has been suggested that the E148Q mutation is the mildest mutation and some reports have questioned its disease association. OBJECTIVE: To evaluate the phenotypic features of the patients with E148Q mutation. SUBJECTS: 26 patients homozygous for E148Q, 10 compound heterozygous for E148Q, and eight complex cases were assessed. RESULTS: Although four of the 26 patients with E148Q/E148Q were asymptomatic at the time of evaluation, abdominal pain was seen in 77% of the patients, fever in 66%, arthralgia in 50%, arthritis in 15.4%, and vomiting in 23.8%. Compound heterozygotes and complex cases had a higher frequency of abdominal pain, fever, arthralgia, arthritis, myalgia, and chest pain than subjects who were homozygous for E148Q, but none of these symptoms reached statistical significance. None of our patients had amyloidosis but two with E148Q/E148Q had a family history of amyloidosis and one had rapidly progressive glomerulonephritis secondary to vasculitis, which progressed to chronic renal failure. CONCLUSIONS: Patients homozygous for E148Q have a heterogeneous clinical presentation. Most are symptomatic and colchicine treatment is required in these patients.

Bone mineral density in children with familial Mediterranean fever.

The aim of this study was to evaluate bone mineral content (BMC), serum and urinary bone turnover parameters in patients with familial Mediterranean fever (FMF), an autosomal recessive disease characterized by recurrent episodes of inflammation of serous membranes. Demographic characteristics and MEFV mutations were defined in 48 children diagnosed with FMF (23 F, 25 M; median age 7.0 years (3.0-10.0)). We evaluated the blood counts, acute-phase proteins and serum and urinary bone turnover parameters during attack-free periods. The BMC and BA (bone area) of vertebrae L1-L4 were measured by DEXA. Thirty-eight age-, sex- and ethnicity-matched healthy children constituted the control group. Mean L1-L4 BMC in Group I (patients with two mutations) and II (patients with no or single mutations) were 15.49+/-5.99 g and 15.68+/-4.89 g, respectively, both significantly lower than the mean L1-L4 BMC of control patients, which was 19.59+/-6.7 g (p<0.05). Mean L1-L4 BMD in Group I, Group II and the control group were 0.466+/-0.066 g/cm(2), 0.487+/-0.085 g/cm(2 )and 0.513+/-0.079 g/cm(2), respectively. Mean z-scores in Group I, Group II and the control group were -1.87+/-0.74, -1.55+/-0.92 and -1.39+/-0.84, respectively. Mean L1-L4 BMD and z-score of Group I were lower than in the control group (p<0.05). ESR and SAA (serum amyloid A) levels were higher in Group I patients: 28.3+/-14.5 mm/h and 350+/-62 mg/l in Group I; and 20.5+/-11.7 mm/h and 190+/-68 mg/l in Group II, respectively. In conclusion, FMF patients had lower BMC, BMD and z-scores than a control group. We suggest that decreased BMD, BMC and z-score in FMF patients may be secondary to subclinical inflammation.

Allelic variants in genes associated with hereditary periodic fever syndromes as susceptibility factors for reactive systemic AA amyloidosis.

We investigated the hypothesis that low-penetrance mutations in genes (TNFRSF1A, MEFV and NALP3/CIAS1) associated with hereditary periodic fever syndromes (HPFs) might be risk factors for AA amyloidosis among patients with chronic inflammatory disorders, including rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), Crohn's disease, undiagnosed recurrent fevers and HPFs themselves. Four of 67 patients with RA plus amyloidosis had MEFV variants compared with none of 34 RA patients without amyloid (P value=0.03). The E148Q variant of MEFV was present in two of the three patients with TNF receptor-associated periodic syndrome (TRAPS) complicated by amyloid in two separate multiplex TRAPS families containing 5 and 16 affected members respectively, and the single patient with Muckle-Wells syndrome who had amyloidosis was homozygous for this variant. The R92Q variant of TNFRSF1A was present in two of 61 JIA patients with amyloidosis, and none of 31 nonamyloidotic JIA patients. No HPF gene mutations were found in 130 healthy control subjects. Although allelic variants in HPFs genes are not major susceptibility factors for AA amyloidosis in chronic inflammatory disease, low-penetrance variants of MEFV and TNFRSF1A may have clinically significant proinflammatory effects.

Decreased prevalence of atopy in paediatric patients with familial Mediterranean fever.

BACKGROUND: A number of inflammatory diseases, including familial Mediterranean fever (FMF), have been shown to be driven by a strongly dominated Th1 response, whereas the pathogenesis of atopic diseases is associated with a Th2 response. OBJECTIVE: Because dominance of interferon gamma has the potential of inhibiting Th2 type responses-that is, development of allergic disorders, to investigate whether FMF, or mutations of the MEFV gene, have an effect on allergic diseases and atopy that are associated with an increased Th2 activity. METHOD: Sixty children with FMF were questioned about allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis, as were first degree relatives, using the ISAAC Study phase II questionnaire. The ISAAC Study phase II was performed in a similar ethnic group recruited from central Anatolia among 3041 children. The same skin prick test panel used for the ISAAC Study was used to investigate the presence of atopy in patients with FMF and included common allergens. RESULTS: The prevalences of doctor diagnosed asthma, allergic rhinitis, and eczema were 3.3, 1.7, and 3.3%, respectively, in children with FMF, whereas the corresponding prevalences in the ISAAC study were 6.9, 8.2, and 2.2%, respectively. Only the prevalence of allergic rhinitis was significantly different between the two groups (p<0.001). The prevalence of atopy in these patients with FMF (4/60 (7%)) was significantly lower than in the children of the population based study (20.6%) (p<0.001). CONCLUSION: Family Mediterranean fever seems to be protective against development of atopic sensitisation and allergic rhinitis.