Familial Mediterranean fever (FMF) is an autosomal recessive disease that is prevalent among eastern Mediterranean populations, mainly non-Ashkenazi Jews, Armenians, Turks, and Arabs. Since a large proportion of all the FMF patients in the world live in Turkey, the Turkish FMF Study Group (FMF-TR) was founded to develop a patient registry database and analyze demographic, clinical, and genetic features. The cohort was composed of 2838 patients (mean age, 23.0 +/- 13.33 yr; range, 2-87 yr), with a male:female ratio of 1.2:1. There was a mean period of 6.9 +/- 7.65 years from disease onset to diagnosis; the period was about 2 years shorter for each decade since 1981. Ninety-four percent of patients were living in the central-western parts of the country; however, their familial origins (70% from the central-eastern and Black Sea regions) reflected not only the ongoing east to west migration, but also the historical roots of FMF in Turkey. Patients' clinical features included peritonitis (93.7%), fever (92.5%), arthritis (47.4%), pleuritis (31.2%), myalgia (39.6%), and erysipelas-like erythema (20.9%). Arthritis, arthralgia, myalgia, and erysipelas-like erythema were significantly more frequent (p < 0.001) among patients with disease onset before the age of 18 years. Genetic analysis of 1090 patients revealed that M694V was the most frequent mutation (51.4%), followed by M680I (14.4%) and V726A (8.6%). Patients with the M694V/M694V genotype were found to have an earlier age of onset and higher frequencies of arthritis and arthralgia compared with the other groups (both p < 0.001). In contrast to other reported studies, there was no correlation between amyloidosis and M694V homozygosity in this cohort. However, amyloidosis was still remarkably frequent in our patients (12.9%), and it was prevalent (27.8%) even among the 18 patients with a disease onset after age 40 years. Twenty-two patients (0.8%) had nonamyloid glomerular diseases. The high prevalence of vasculitides (0.9% for polyarteritis nodosa and 2.7% for Henoch-Schonlein purpura) and high frequency of pericarditis (1.4%) were striking findings in the cohort. Phenotype II cases (those patients with amyloidosis as the presenting or only manifestation of disease) were rare (0.3% or less). There was a high rate of a past diagnosis of acute rheumatic fever, which suggested a possible misdiagnosis in children with FMF presenting with recurrent arthritis. To our knowledge, this is the largest series of patients with FMF reported from 1 country. We describe the features of the disease in the Turkish population and show that amyloidosis is still a substantial problem.

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These results confirmed the presence of autonomic dysregulation in children with breath-holding spells. Iron deficiency may have an impact on this autonomic dysregulation. Ventricular repolarization was unaffected in patients with breath-holding spells.

KD must be kept in mind in the differential diagnosis of infants with prolonged fever.

Cardiovascular abnormalities are observed in most children with end-stage renal disease (ESRD). The aim of this study was evaluation of left-ventricular (LV) myocardial performance using tissue-Doppler imaging (TDI) in patients with ESRD. Twenty-five patients with ESRD and 25 healthy gender- and age-matched control subjects were assessed with conventional M-mode echocardiography, pulsed-wave Doppler (PWD), and TDI. Myocardial Performance Index (MPI) and LV mass index (LVMI) were calculated. MPI and conventional echo-Doppler indices were compared in the ESRD and control groups. Significant differences were present in the mean systolic and diastolic blood pressure (BP) between children with ESRD and healthy children (p = 0.007 and p < 0.001, respectively). The mean LVMI was significantly greater in the patient group (p < 0.001). The tissue-Doppler MPI of patients was significantly higher than that in healthy children (p < 0.001). LVMI was significantly correlated with systolic and diastolic BP. MPI obtained by TDI was significantly correlated with LVMI. Our study confirms that LV dysfunction is present in patients with ESRD and hypertension is an important risk factor.

Heterozygous mutations in the NKX2-5 gene of patients with various congenital heart defects have been reported. Most of the congenital heart defects associated with the mutations in the NKX2-5 gene are conotruncal heart anomalies, primarily the tetralogy of Fallot. In this study, the authors screened 72 Turkish children with conotruncal heart anomalies and 185 healthy control subjects to find the NKX2-5 alterations. They found one previously documented NKX2-5 missense alteration, heterozygous c.73C>T (p.Arg25Cys), in a 10-year-old boy with tetralogy of Fallot. The same heterozygous alteration was found also in the patient's healthy father and in two unrelated persons in the healthy control group. The current study shows for the first time the presence of p.Arg25Cys in healthy control subjects other than African Americans. These results show that no genetic support exists for the pathogenecity of this alteration, although a previous in vitro study and theoretical predictions suggest a structural/functional difference in the altered protein region.

In order to determine the role of levels of acute phase proteins (APPs) for the development of amyloidosis in familial Mediterranean fever (FMF) patients, the levels of serum amyloid A (SAA), C reactive protein (CRP), fibrinogen and erythrocyte sedimentation rate were measured in paired sera of 36 FMF patients during and in between acute attacks, 39 of their healthy parents (obligate heterozgotes), and 15 patients with FMF associated amyloidosis. To compare the levels of APPs, 39 patients with chronic infections or inflammatory diseases who may develop secondary amyloidosis, 20 patients with acute infections who are known to have elevated acute phase response but will never develop amyloidosis and 19 healthy controls were included. The median levels of all APPs are increased in the patients with FMF during attacks and a significant decrease was observed after the attack was over. The level of SAA was above reference range in all FMF patients during the attack free period and the level of at least one other APP was also above normal in 64% of the patients. Both CRP and SAA levels were found to be higher in obligate heterozygotes compared to controls. The levels of SAA in patients with FMF during the attack-free period, obligate heterozygotes and patients with FMF-amyloidosis were found to be similar. The levels in each group were found to be higher than SAA levels found in healthy controls yet lower than the levels measured in the patients with acute infections and patients with chronic inflammation or chronic infections. In conclusion, our results show that SAA level reflects subclinical inflammation with high sensitivity but its value for the prediction of amyloid formation process seems to be low.

In neonates, the diastolic and systolic myocardial velocities of the left ventricle were significantly lower than those measured in the children group. Decreased myocardial tissue values of neonates might be reflecting the immaturity of neonatal myocardium.