Different clinical presentation of the hyperimmunoglobulin D syndrome (HIDS) (four cases from Turkey)

Hyperimmunoglobulin D syndrome (HIDS) is one of the autoinflammatory syndromes which are characterized by febrile attacks. Duration and frequency of the febrile attacks, as well as typical organ involvements vary greatly. Recently, it is possible to reach more reliable data by the possibilities that are opened up by molecular genetics in order to highlight the aetiopathogenesis of this group of diseases. Typical patients with HIDS have an onset of disease in the first year of life. Here, we report four Turkish HIDS cases; three of whom, the symptoms started at a later age. The diagnoses were made by relevant clinical symptoms along with MVK mutations detected by DNA sequencing method. As summarised in this article, HIDS could be presented with a broad spectrum of symptoms. Although most of the HIDS patients are reported from Europe and especially Dutch ancestry, case reports are presented from all over the world. For this reason, HIDS should be kept in mind for the differential diagnosis of periodic fever syndromes or before accepting an FMF patient as colchichine resistant. We suppose that the phenomenon of “later-onset HIDS” should shed light into unresolved clinical problems of patients with periodic fever. Especially in countries that FMF is more frequent such as Turkey, even though the symptoms start later than classic cases, HIDS should be kept in mind for differential diagnosis of periodic fever syndromes.     

Hyperhomocysteinemia and end-stage renal disease: determinants and association with cardiovascular disease in Tunisian patients.

The study reports on plasma total homocysteine (tHcy) levels in Tunisian patients with chronic renal failure (CRF) and those treated with hemodialysis (HD) and renal transplant (RT). The aims of the study were to identify the determinants of tHcy concentration and to test the association between hyperhomocysteinemia and atherothrombotic disease in end-stage renal disease (ESRD). A total of 35 CRF patients on conservative treatment, 50 HD patients, and 30 RT recipients, and 31 age- and sex-matched healthy subjects were included. Plasma tHcy was assessed by a fluorescent-polarizing immunoassay method. Multivariate analysis was applied to identify the main determinants of tHcy concentration and to assess the relationship between hyperhomocysteinemia and cardiovascular disease. Plasma mean tHcy concentration was significantly increased (p < 0.001) in CRF patients (mean +/- SD) (28.9 +/- 9.8 micromol/l), in HD patients (29.4 +/- 11.1 micromol/l), and in RT (19.3 +/- 6.3 micromol/l) patients compared to controls (11.9 +/- 4.1 micromol/l). Multivariate analysis using GLM ANOVA modeling demonstrated that tHcy was significantly higher in males (p = 0.02), and was related to age (p = 0.008), albumin (p = 0.005), vitamin B12 (p = 0.002), folate (p = 0.00001), and creatinine clearance (p = 0.0008). However, tHcy was not associated with C-reactive protein and did not significantly differ between CRF, HD, or RT patients. The upper quartile of tHcy concentration was significantly associated with atherothrombotic cardiovascular disease (unadjusted odds ratio (OR) = 3.09; 95% CI, 1.11-8.61; p = 0.01). This association remained significant after adjusting for sex, age, hypertension, and smoking (multi-adjusted OR = 4.78; 95% CI, 1.92-11.9; p = 0.0008). The mean tHcy concentration was 2 to 3 times higher in ESRD patients than in subjects with normal renal function. This increase could be related to glomerular filtration rate reduction and functional B vitamins deficiency, but was not associated with inflammation. The upper quartile of tHcy concentrations confers 4.78-fold increased independent risk for atherothrombotic events in ESRD patients.     

VEGF 936 C/T gene polymorphism in renal transplant recipients: association of the T allele with good graft outcome

We investigated the possible impact of vascular endothelial growth factor (VEGF) 936 C/T gene polymorphism on kidney graft outcome. DNA samples of 290 first deceased donor kidney graft recipients with well-functioning grafts and no rejection treatment during the first transplant year (WFG), 265 recipients with graft failure within the first transplant year (F), and 187 healthy control subjects were tested using the polymerase chain reaction restriction fragment length polymorphism technique. Although VEGF 936 CT genotype and T allele carrier frequencies in 555 kidney graft recipients did not differ significantly from frequencies observed in healthy control subjects, significantly higher frequencies were found in WFG patients (CT: 19.0%, T: 20.7%) than in F patients (CT: 11.7%, p=0.019; T: 12.8%, p=0.017, respectively). The VEGF 936 CT genotype and T allele appear to be associated with good outcome in renal transplantation and, if confirmed, might be helpful for the pretransplant identification of recipients with low risk of graft rejection.     

Methylmalonic acidemia and hyperglycemia: an unusual association

Introduction: Hyperglycemia is an exceptional manifestation of methylmalonic acidemia (MMA). We describe a patient with MMA in whom we observed a hyperglycemia which improved under treatment of the metabolic crisis. Case report: A 14 month-old boy presented with an acute generalized dystonia and lethargy preceded by fever, vomiting and lethargy at the age of 13 months. Biological investigations showed a hyperglycemia, a lactic acidosis and a hyperammonemia. Urinary organic acid analysis showed accumulation of methylmalonic acid, tiglylglycine and methylcitrate leading to the diagnosis of MMA. The patient underwent symptomatic treatment with rapid improvement of general condition, consciousness and gradual normalization of biological parameters especially glycemia after 6 days without using insulinotherapy. Discussion: MMA is an autosomal recessive disorder caused by a deficiency of methylmalonyl-CoA mutase resulting in methylmalonic acid accumulation. Biochemically, the disorder is typically characterized by: metabolic acidosis, ketonemia or ketonuria, hyperammonemia, leukopenia, thrombocytopenia and anemia. Hypoglycemia is a frequent manifestation of MMA. Our patient presented a hyperglycemia, which is unusual in MMA, since we found only three patients reported with this association. Pathophysiology remains unknown. In reported cases, hyperglycemia was treated by insulin therapy and reducing glucose intravenous infusion, with fatal outcome. In our patient glycemia spontaneously normalized after treatment of the metabolic crisis. Conclusion: Hyperglycemia is an exceptional manifestation of MMA and could be a seriousness marker.     

Hb A2-Pasteur-Tunis [delta59(E3)Lys-->Asn, AAG-->AAC]: a new delta chain variant detected by DNA sequencing in a Tunisian carrier of the codon 39 (C-->T) beta0-Thalassemia mutation

We describe a new delta-globin variant, Hb A2-Pasteur-Tunis [delta59(E3)Lys-->Asn, AAG-->AAC]. This hemoglobin (Hb) displayed an electrophoretic mobility faster than normal Hb A2 and was expressed at 2.2 %. The molecular defect was characterized by DNA sequencing and confirmed by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-designed protocol. Hb A2-Pasteur-Tunis was found in a carrier of a codon 39 (C-->T) beta0-thalassemia (thal), presenting with a normal Hb A2 level. Phenotype and genotype investigations revealed that the total Hb A2 level of the patient was that expected for a minor beta-thal (4.8%).     

Avascular osteonecrosis and accompanying anemia, leucocytosis, and decreased bone mineral density in renal transplant recipients

Background

Avascular osteonecrosis (AVN) is a complication of renal transplantation. In this study, we present 12 cases of AVN associated with renal transplantation.

Methods

Renal transplant recipients (RTRs) with AVN (group I [GI]) were evaluated by using magnetic resonance imaging and blood urea nitrogen, creatinine, glucose, calcium, phosphorus, magnesium, alkaline phosphatase, parathyroid hormone, and urine analysis. We evaluated bone mineral density (BMD) of the femoral neck and lumbar vertebrae. All patients were treated with steroids, cyclosporine, or tacrolimus plus mycophenolate mofetil. Twenty-six RTRs (GII) without AVN were randomly selected as control subjects.

Results

The mean ages of GI and GII, were 33.81 ± 6.72 and 34.00 ± 7.65 years respectively (P > .05). The mean interval between transplantation and development of AVN was 12.08 ± 6.48 months. Although levels of blood urea nitrogen, creatinine, calcium, magnesium, and parathyroidhormone, as well as glucocorticoid doses in the first 12 months were similar in GI and GII, there were significant differences in serum alkaline phosphatase, hemoglobin levels, and white blood cell count between GI and GII (P < .05 for each). BMD T score <−1.5 was observed in 8/9 GI and 15/26 patients in GII. All of the patients with AVN except 1, were followed with conservative measures including calcium, magnesium, and vitamin D replacement therapies, bisphosphonate, and reduced or ceased glucocorticoid treatment. Although T scores of the femoral head were similar in GI and GII, the lumbar vertebral T score was significantly lower in GI than in GII (P < .052).

Conclusion

AVN developed within the first year after transplantation. Decreased lumbar vertebral BMD, which can be an indicator of glucocorticoid effect, accompanied AVN in nearly all patients. Despite the absence of renal dysfunction, increased bone destruction, anemia, and leucocytosis were coincidental or accompanying findings in our patients with AVN.     

Copeptin levels predict left ventricular systolic function in STEMI patients: A 2D speckle tracking echocardiography-based prospective observational study

In the present study, we aimed to investigate whether copeptin values on admission are related to left ventricle (LV) systolic function and its improvement at 6 months in ST-segment elevation myocardial infarction (STEMI) patients.In this single-center, prospective observational study, we included 122 STEMI patients from January 2016 to November 2016. LV systolic functions in the form of global longitudinal strain (GLS) in addition to conventional echocardiography parameters were evaluated on admission and at 6-month. Serum copeptin levels were determined using an ultrasensitive immunofluorescence assay.The study population was divided into 2 groups according to median values of copeptin. GLS was significantly lower in patients with high copeptin levels compared to those with low copeptin levels at early stage and 6-month (−16% (16–16.5) vs −15% (15–15.5), P < .001 and −18% (18–19) vs −16% (16–16.25), P < .001, respectively). Copeptin values were negatively correlated with an early and 6-month GLS (r = –0.459 at early stage and r = –0.662 at 6-month). In addition, we observed that copeptin values were negatively correlated with the improvement of GLS at 6-month follow-up (r = −0.458, P < .001 and r = −0.357, P = .005, respectively).Serum copeptin levels in STEMI patients at the time of admission may predict early and 6-month LV systolic function assessed by two-dimensional GLS. To the best of our knowledge, this study is the first to specifically address the relationship between copeptin values and GLS in STEMI patients.     

Parasitic arthritis induced by Strongyloides stercoralis.

A 40-year-old man presented with palpable purpura and symmetrical polyarticular arthritis. Histological examination of the synovial membrane and fluid unexpectedly disclosed Strongyloides stercoralis infestation of the ankle joint.