Meropi Dimitriadou

Poor correlations between measurements of bone quality by quantitative ultrasound sonography and dual energy X‐ray absorptiometry in patients with β‐thalassaemia major

Objectives:  Osteopenia/osteoporosis is a major component of morbidity even in young patients with β‐thalassaemia major. Dual energy X‐ray absorptiometry (DXA) is the reference method for determining bone mineral density (BMD). Quantitative ultrasound sonography (QUS) for bone measurement is a relatively new, inexpensive and radiation‐free method that could serve as an alternative to DXA. Our aim was to assess bone status in thalassaemic patients both with QUS and DXA and, consequently, to investigate the degree of correlation between the two methods.

Elevated serum parathormone levels are associated with myocardial iron overload in patients with β-thalassaemia major

Objectives:  Despite advances in conventional treatment, iron‐induced cardiomyopathy is still the most frequent cause of death among patients with β‐thalassaemia major. Recent studies have correlated increased myocardial iron content to decreased levels of vitamin D in thalassaemic patients. The aim of this study was to measure parathormone (PTH) and metabolites of vitamin D and consequently to investigate whether these parameters predispose to myocardial iron overload in patients with β‐thalassaemia major.

Restrictive pulmonary dysfunction and its predictors in young patients with β-thalassaemia major.

Pulmonary dysfunction represents one of the most undervalued and less recognized complications in patients with β‐thalassaemia.

Fok-I polymorphism of vitamin D receptor gene and the presence of renal dysfunction in patients with β-thalassemia major.

Recent evidence supports the presence of renal dysfunction even among young patients with β-thalassemia major. However, the possible genetic contribution has never been investigated. The aim of this study was to correlate the presence of Fok-I polymorphism of the vitamin D receptor gene with abnormal levels of early markers of renal impairment in children and young adults with thalassemia. Thirty-four patients (19 male and 15 female) with β-thalassemia major on conventional treatment, with a mean decimal age of 14.62 ± 5.47 years (range: 5–22 years), were included in the study. Markers of renal function were determined in serum and in urine and patients were genotyped for Fok-I gene polymorphism. Genotype frequencies were similar to those previously reported for other populations: 47.06% of the patients were homozygous for the F allele, 41.18% were heterozygous, and 11.76% were homozygous for the f allele. A considerable number of patients demonstrated impaired renal function with increased serum cystatin C levels (29.41%), glomerular dysfunction with proteinuria (68%), as well as significant tubulopathy with hypercalciuria (73.08%), and increased levels of urinary β2-microglobulin (29.41%). When patients were stratified according to Fok-I polymorphism, a significantly higher prevalence of abnormally increased serum levels of cystatin C was observed in patients being homozygous for the f allele (75%) compared with those being heterozygous (Ff) or homozygous for the F allele (14.29% and 31.25%, respectively, P = .02). Further studies are needed to confirm these preliminary results and elucidate the possible mechanisms involved.

Fok‐I gene polymorphism of vitamin D receptor in patients with beta‐thalassemia major and its effect on vitamin D status

Abstract Most of the biological actions of vitamin D are mediated by an intracellular receptor (VDR) in which several single nucleotide gene polymorphisms have been identified. Vitamin D deficiency is increasingly identified among thalassemic patients and recent evidence links it with myocardial iron accumulation. The aim of this work was to assess the distribution of the Fok‐I polymorphism of the VDR gene among Greek children and young adults with beta‐thalassemia major and to investigate its association with 25(OH)D3 and 1,25(OH)2D3 serum levels. Sixty‐nine thalassemic patients (35 females and 34 males), with a mean age of 23·05±6·07 years, participated in the study. Genotype frequencies of Fok‐I were similar to those previously reported for other populations; 44·9% of the patients were homozygotes for F allele, 43·5% were heterozygotes and 11·6% were homozygotes for the f allele. Low levels of serum 25(OH)D3 were recorded, as 41 patients (59·4%) were below the cut‐off limit of 50 nmol/l that determines deficiency, whereas, levels of 1,25(OH)2D3 showed wide variability ranging from deficiency (⩽50 pmol/l) in 34 patients (49·3%) to excess (⩾125 pmol/l) in 13 patients (18·8%). When stratifying patients according to serum 1,25(OH)2 D3 concentrations, a higher prevalence of the f allele was observed in the deficiency group (P = 0·03). A comparison of the serum concentrations of the two vitamin D metabolites produced a trend towards a negative correlation (r = −0·204, P = 0·09). Further studies are required to assess the genetic contribution to the regulation of vitamin D metabolites in the serum of patients with beta‐thalassemia major.

A novel MKRN3 nonsense mutation causing familial central precocious puberty

Central or gonadotropin-dependent precocious puberty (CPP) caused by early activation of pulsatile Gonadotropinreleasing hormone (GnRH) secretion is clinically defined by the early maturation of the entire hypothalamic-pituitarygonadal axis and the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys [1]. Pubertal timing and growth are influenced by complex interactions of genetic, nutritional, environmental, and socioeconomic factors [2]. Epidemiological studies suggest that around 60–80% of the variation in pubertal onset might be genetically determined [3]. Additionally, family history of CPP has been identified in up to 27.5% of cases with an autosomal mode of inheritance [4]. To date, only a handful of genes, involving both the excitatory and the inhibitory pathways of GnRH secretion, have been reported as causative for CPP and mutations were identified in the kisspeptin system kisspetin 1 (KISS1) and its receptor (KISS1R) [5, 6], and in the makorin RING-finger protein 3 (MKRN3) gene [7]. The initial report by Abreu et al. [7], describing 3 MKRN3 gene frameshift mutations predicted to encode truncated proteins and one missense mutation predicted to disrupt protein function in 2013, was followed by a few more reports of novel loss-of-function mutations resulted to MKRN3 protein deficiency and premature initiation of puberty [8–16]. In the present study, we aimed to identify possible genetic cause in a familial case of CPP in which three out of four girls were affected. The parents were not consanguineous; mother had menarche at normal age (12.5 years), whereas father was considered as an “early developer” although without documentation, but with a final height that is below his midparental height. The proband (Patient II.1, Fig. 1a) was presented with thelarche in 2004 at the age of 6.5 years, the second girl (Patient II.2, Fig. 1a) was presented with thelarche (Tanner staging for breast development: B2) at the age of 8.5 years, whereas the twin, non-monozygotic, younger girls (Patients II.3 and II.4, Fig. 1a) exhibited precocious puberty recently with an interval of 5 months at the ages of 5.1 and 5.6 years respectively. In all affected girls, GnRH stimulation tests were performed by standard techniques and they were all indicative of CPP (Luteinizing hormone (LH) peaked at 18.7, 23.2, and 19.4 μU/ml for the 1st, 3rd, and 4th girl, respectively) and subsequent magnetic resonance imaging (MRI) of the hypothalamic-pituitary region revealed no underlying pathology. The proband started therapy with a long-acting triptorelin and maintained it until the age of 11 years, had menarche at the age of 12.6 years with regular pattern of menses since then. The twin sisters have recently commenced treatment with long-acting triptorelin. Informed consent from the parents and the older sister was obtained in accordance to the national laws. Genomic DNA was extracted from peripheral blood leukocytes samples of the siblings and parents participating * Athanasios Christoforidis christoforidis@doctors.org.uk

Sizeable acquired subglottic cyst in a baby with Williams-Beuren syndrome: association or coincidence?

We describe a case of an acquired subglottic cyst presented with persistent stridor and voice hoarsening in a baby diagnosed with Williams-Beuren syndrome that was born premature and required intubation during neonatal period. We also comment on whether this is a coincidence or there can be an association between impaired elastogenesis, a feature of patients with the syndrome and the formation of a subglottic cyst.

Glucose Levels Before the Onset of Asparaginase Predicts Transient Hyperglycemia in Children With Acute Lymphoblastic Leukemia

Transient hyperglycemia (TH) represents an acknowledged adverse event that occurs during treatment in children with acute lymphoblastic leukemia (ALL) and has recently been associated with an increased risk for developing metabolic disturbances in future life. Our aim was to estimate the incidence of TH and to identify risk factors, thus serving as markers for identifying candidates for prevention interventions.

Cross-sectional study of pulmonary function and MRI-derived liver and myocardial iron content in young patients with β-thalassemia major

To the Editor: Pulmonary dysfunction stands for one of the most undervalued and less recognized complications in patients with b-thalassemia, although it has initially been described almost three decades ago (1). Conflict reports exist regarding the type of the observed pneumonopathy (2, 3), and the exact pathogenetic mechanism is not clearly elucidated; however, the chronic effect of iron overload may reasonably intervene in it. In this report, we present findings from a study that we have conducted to cross-sectionally investigate the type of pulmonary dysfunction as assessed by means of spirometry and in correlation with the level of iron accumulation within the liver and the myocardium as determined by MRI in a cohort of children and young adults with b-thalassemia major. Thirty-nine thalassemic patients on conventional treatment (19 men and 20 women) with a mean decimal age of 21.69 ± 6.13 years (range: 9–34 years) were recruited for the study. Myocardial and hepatic iron concentrations were quantified using standard MRI methods as previously described (4). Pulmonary function was evaluated using spirometry and measurements of lung volumes, and diffusion capacity was carried out by a complete computerized pulmonary function testing system. All measurements were performed 3–5 days after a scheduled blood transfusion to ensure hemodynamic stability. Pulmonary function results were expressed as percentages of predicted normal values provided by the device’s manufacturer and corrected for age, sex, and height. The threshold of abnormality was determined as below 80% of the predicted value. Finally, data including the history of splenectomy, serum ferritin levels, and the amount of red blood cells transfused for 1 year prior to the study were collected from each patient’s medical file. Fourteen patients (35.9%) had restrictive pulmonary pattern, whereas no patient was identified as having obstructive or mixed airway disease. Diffusional impairment characterized by significantly lower DLCO*% values (carbon monoxide diffusion capacity of the lung) was observed in 59% of the patients and in the 93% of the patients having a restrictive pulmonary pattern. When patients were categorized according to their normal or restrictive spirometric pattern, only age differed significantly (P < 0.001) between the two groups formed (Table 1). Patients with restrictive pulmonary pattern had increased liver iron content as detected by MRI (mean MR relaxation time: 5.59 ± 5.48 msec) compared to patients with normal pulmonary function (10.76 ± 10.33 msec), with a difference that was approaching statistical significance (P = 0.095). Neither myocardial iron nor cardiac ventricular volumes or ejection fractions differ between the two groups. No correlations were observed between myocardial MR values, liver MR values, and parameters obtained from pulmonary function testing. As expected, only liver MR values were inversely correlated to serum ferritin concentrations (r = )0.398, P = 0.012). Interestingly enough, ferritin was inversely correlated to DLCO*% (r = )0.336, P = 0.036), but with no other spirometric parameter.

Level of Internet use among Greek adolescents with type 1 diabetes

Abstract Background Compulsive Internet use has emerged as a contemporary addictive behavior. Our aim was to investigate the reasons for Greek adolescents with type 1 diabetes mellitus (T1DM) and their families to use the Internet and additionally to investigate the level of Internet use and its associations to demographic, socio-economic parameters and glycemic control. Methods Patients with T1DM, aged >12 years and their parents were recruited during their regular visits to the Pediatric Diabetes Clinic. A similar group of healthy children, age- and sex-matched served as a control group. All participants were asked to fill out the Greek translated version of the Internet Addiction Test (IAT). Caregivers of patients with T1DM were asked to complete a second questionnaire consisting of questions regarding demographic and socio-economic data of the family and data concerning disease management. Results Thirty-five patients with T1DM (mean decimal age of 14.95 ± 1.90 years) and 35 controls participated in the study. Nine patients were on an insulin pump whereas the rest were on multiple daily injections. The mean total score of the patients’ IAT questionnaires was significantly lower compared to the controls (26.26 ± 12.67 vs. 39.91 ± 18.55, p = 0.003). Controls were characterized as exhibiting moderate addictive behavior at a significantly higher percentage than patients (31.43% vs. 2.86%, p = 0.002). All patients on insulin pumps demonstrated normal Internet use. Mild addictive behavior was associated with a lower parental educational level. Finally, level of Internet use (IAT score) was positively associated to glycemic control (HbA1c value) with a correlation that was approaching significance (r = 0.315, p = 0.065). Conclusions Adolescents with T1DM and especially those on an insulin pump exhibit normal Internet use compared to their healthy peers. Time consumed on Internet correlates reversibly with glycemic control.