Ewa Barg

A new case of cerebro-facio-thoracic dysplasia in a 3-year-old girl with short stature and hypothyroidism.

Introduction Cerebro-facio-thoracic dysplasia (CFTD) is a genetic syndrome of unknown cause, characterized by typical facial dysmorphic features, and psychomotor and intellectual disability, along with brain malformations as well as multiple skeletal defects, including rib and vertebral abnormalities. Autosomal recessive inheritance has been suggested (Pascual-Castroviejo et al., 1975; Philip, 1992; Guion-Almeida et al., 1996; Rufo-Campos et al., 2004; Cilliers et al., 2007).

Congenital hyperinsulinism in Polish patients - how can we optimize clinical management?

INTRODUCTION Congenital hyperinsulinism of Infancy (CHI) comprises heterogenic defects of insulin secretion with diverse molecular aetiology, histological features, severity of symptoms, and response to pharmacotherapy. The study aimed to establish the first clinical characteristics of Polish patients with CHI and to propose a novel clinical algorithm allowing the prioritisation of genetic and radiology studies, based on patients characteristics and response to pharmacotherapy. MATERIAL AND METHODS Thirty-one patients with CHI were recruited from five reference centres in Poland. Clinical and biochemical parameters were statistically evaluated and compared to those of a control group (n = 30). RESULTS CHI predisposes to increased birth weight (p = 0.004), lower Apgar score (p = 0.004), perinatal complications (74%), and neurological implications (48%). Diagnostic process and therapy were inconsistent. A trial of pharmacotherapy was applied in 21 patients (68%), and diagnostic imaging with 18F-L-DOPA PET was performed in only 3. Eighteen patients (58%) were surgically treated, including 8 infants (44%) aged less than 2 months. Depending on the type of resection, further hypoglycaemia was observed postoperatively in 50% (n = 9) and hyperglycaemia in 39% (n = 7) of cases. Based on foregoing results, a clinical algorithm was proposed. CONCLUSIONS Standardisation of clinical management with the use of pharmacotherapy, genetic screening, and diagnostic imaging will allow the optimisation of therapy and minimisation of treatment complications.

Familial distal monosomy 3p26.3-pter with trisomy 4q32.2-qter, presenting with progressive ataxia, intellectual disability, and dysmorphic features.

We present a boy diagnosed with partial 3p monosomy and partial 4q trisomy. The patient was 9 years of age with intellectual disability, dysmorphic features, and ataxia. A family history and medical evaluation showed that the father manifested similar facial dysmorphic features, intellectual disability, quadriparesis, and progressive cerebrospinal ataxia. The chromosomal aberration found in the proband was inherited from his father who was found to have a balanced reciprocal translocation of chromosomes 3p and 4q, which was in turn inherited from the paternal grandfather. The final cytogenetic diagnosis according to microarray was 46,XY,der(3)t(3;4)(p26.1;q32.2)arr 3p26.1(39,066–5,363,502)x1,4q32.2q35.2(162,555,236–191,173,881)x3. We describe the cytogenetic investigations that led to the identification of the breakpoints. In addition, we present an overview of the clinical features found in patients with partial 3p monosomies and partial 4q trisomies as reported in the literature.

Zespół Polanda u 12-letniej dziewczynki – opis przypadku

Zespol Polanda obejmuje jednostronny brak mieśnia piersiowego wiekszego i anomalie homolateralnej konczyny gornej. Zwykle wspolistnieją: brak brodawki sutkowej i aplazja/hipoplazja gruczolu sutkowego. Mogą towarzyszyc anomalie nerki, a takze nowotwory. W pracy przedstawiono 12-letnią dziewczynke z cześciowym zespolem Polanda w postaci lewostronnego braku mieśnia piersiowego oraz homolateralnej hipoplazji brodawki sutkowej i aplazji gruczolu sutkowego, bez anomalii konczyny gornej. Stwierdzona anomalia ukladu mieśniowego nie stanowi istotnego obciązenia organizmu, konieczne są regularne cwiczenia usprawniające, celem wzmocnienia mieśni obreczy barkowej. Natomiast brak gruczolu piersiowego stanowi wskazanie do zabiegu rekonstrukcyjnego piersi po zakonczeniu procesu wzrastania.

Impact of SIRT1 gene expression on the development and treatment of the metabolic syndrome in oncological patients

Sirtuins - products of gene SIRT expression have been divided into 7 classes, according to the amino acid composition and location of the cell. Those factors, called longevities proteins, are a group of histone deacetylases, depend on nicotinamide adenine dinucleotide (NAD). Particularly noteworthy is the protein sirtuin 1, which further deacetylates numerous transcription factors, receptors and enzymes. Through its action reduces the activity of glucocorticoid receptors in the body. Products of gene SIRT1 expression is responsible for apoptosis, differentiation, senescence cells, also affect the regulation of carbohydrate and lipid metabolism. Cardioprotective and hypotensive impact is also very important. SIRT1 reduces the accumulation of fat and decreases the risk of visceral obesity. Low gene expression of SIRT1 therefore predispose to the development of metabolic syndrome. Homeostasis sirtuin 1 disorders can also be observed in certain neoplastic diseases, primarily hormone-dependent breast, ovarian and prostate cancer, as well as it can cause leukemias and lymphomas. Components, activating expression of gen SIRT1 or a molecule with biological properties sirtuin 1, may have promising impact for treatment of diabetes mellitus type 2, obesity, hypertension, dyslipidemia. Analyzing, the pleiotropic effect of sirtuin 1 and numerous metabolic pathways, appear to be particularly beneficial effect of supplementation molecules increasing the level of expression gene SIRT1, in treatment of acute lymphoblastic leukemia with using high-dosing glicocorticosteroid therapy. Which would reduce the number of early and late complications of oncological treatment and increase patient survival. Compound requires further study.

Vitamin D and metabolic, autoimmunologic and neoplasm diseases

At the turn of the 19th and 20th century McColum made the discovery of vitamin D as a result of the research on cod liver oil, in order to identify substances having anti ricets effect. Since that time, knowledge of its role in the human body systematically increases. For many years it was thought that it only plays a role in regulating calcium economy. The discovery in the mid-1970s of the presence of VDR- Vitamin D Receptor in most cells of the human body have turned attention to its pleiotropic effect. Special attention deserves wit. D impact on the risk of metabolic diseases and of pre-neoplasia as well as the long-term effects of the treatment of these diseases. The article presents a short review of the results of previously conducted studies on these issues.

[The use of metabolomics in medicine - some examples of oncological and metabolic diseases].

Metabolomics is a new field of medicine focused on examining and analyzing metabolites produced in biological cells. Biological fluids primarily used in this method include: plasma, cerebrospinal fluid, saliva and urine. The most common methods of evaluating the composition involve nuclear magnetic resonance (NMR) and magnetic resonance (MR) with addition of gas chromatography (GC-MS) or liquid chromatography (LC-MS). Metabolomics is used in a wide variety of medicine disciplines. The variability of biochemical processes in tumor cells in comparison to normal cells is the starting point of such studies. The metabolomic changes are observed not only in solid tumors, like the mammary tumor, ovarian cancer, prostate cancer but also in tumors of the hematopoietic and lymphoid tissues. Nowadays, the aim of studies is to find biomarkers which would help to diagnose a disease quickly, assess its progression, and implement effective treatment. Metabolomics is also widely applied in metabolic diseases, mainly the diabetes. The list of examined metabolites gives promising chances for a successful prognosis, diagnosis and comprehensive monitoring of the progression of this civilization disease. The development of metabolomics will also contribute to the individualization of treatment, proper drugs adjustment, which will make a therapy more successful, cause less side effects and improve the quality of patients life.

Indices of insulin resistance and dyslipidemia are correlated with lymphocyte proneness to apoptosis in obese or overweight low birth weight children.

Aims: Our aim was to study the relationship between markers of cell proneness to apoptosis and indices of insulin resistance and dyslipidemia in children born with low birth weight (LBW). Methods: The study comprised 177 prepubertal children stratified by birth weight and their nutritional status into LBW (n = 138) and normal birth weight (NBW; n = 39) groups. We analyzed DNA from peripheral blood lymphocytes, separated by pulsed-field gel electrophoresis (PFGE), as well as the serum levels of cholesterol, HDL-cholesterol, triglycerides, fasting insulin and glucose, caspase 3, and BCL2. Results: LBW children with a BMI SDS >1.55 demonstrated increased content of the large fragments of the lymphocyte DNA [300-500 kb (DNA300-500 kb)] in electrophoretic slides (a marker of decreased chromatin stability and susceptibility of cells to apoptosis) compared to the NBW group. In these children the level of DNA300-500 kb exhibited a strong negative correlation with the serum level of antiapoptotic protein of BCL2 (r = -0.901). DNA300-500 kb significantly correlated with calculated indices of insulin resistance: HOMA-IR and QUICKI as well as with the indices of lipid homeostasis (Castelli and AIP). Conclusions: Increased susceptibility of lymphocytes to apoptosis correlated with a higher risk of insulin resistance and lipid disturbance in overweight or obese LBW children. A comprehensive study of the proneness of cells to apoptosis should be implemented to further investigate the pathomechanism of the metabolic syndrome in these children.

Treatment of severe primary IGF-1 deficiency using rhIGF-1 preparation – first three years of Polish experience

INTRODUCTION The objective of this study was to analyse the effects of the first three years of treatment with recombinant human insulinlike growth factor 1 (rhIGF-1) in patients from the Polish population. MATERIAL AND METHODS Twenty-seven children (22 boys and five girls) aged 2.8 to 16.0 years old were qualified for treatment with rhIGF-1 (mecasermin) in different treatment centres, according to Polish criteria: body height below -3.0 SD and IGF-1 concentration below percentile 2.5 with normal growth hormone (GH) levels. Mecasermin initial dose was 40 μg/kg bw twice a day and was subsequently increased to an average of 100 μg/kg bw twice a day. Body height, height velocity, weight, body mass index (BMI), and adverse events were measured. RESULTS Mecasermin treatment resulted in a statistically significant increase in body height (1.45 ± 1.06 SD; p < 0.01) and height velocity in comparison with pre-treatment values. The biggest change in height velocity happened during the first year and diminished during subsequent years. Body weight and BMI also increased significantly after treatment (1.16 ± 0.76 SD and 0.86 ± 0.75 SD, respectively; p < 0.01). Eight patients reported adverse events. These were mild and temporary and did not require treatment modification except in two patients. CONCLUSIONS Treatment with rhIGF-1 was effective and safe in Polish patients with primary IGF-1 deficiency. It had a clear beneficial effect on the height of the patients and significantly accelerated the height velocity, particularly in the first year of treatment.

Evaluation of selected endocrine disorders after anticancer treatment of solid tumors in childhood.

Wstęp. Coraz skuteczniejsze metody leczenia nowotworów wieku dziecięcego wpływają na lepszą przeżywalność, ale są przyczyną powstawania odległych następstw leczenia. Celem pracy jest ocena częstości występowania wybranych zaburzeń endokrynologicznych. Materiały i metody. Grupę badaną stanowiło 74 pacjentów (48 chłopców), w wieku 3,25-27 lat (średnia 13.24±6.21), co najmniej rok po zakończeniu leczenia przeciwnowotworowego z powodu guzów litych. Oceniono funkcję tarczycy, stężenie gonadotropin, lipidogram (cholesterol/LDL/TG, HDL) oraz BMD (z-score). Oceniono również parametry antropometryczne: wysokość SDS, masę ciała SDS oraz BMI SDS. Wyniki. Zaburzenia endokrynologiczne występowały u 66 (89,19%) pacjentów. U większości pacjentów (66,57%) obserwowano jedno lub dwa zaburzenia. Najczęstszymi nieprawidłowościami były dyslipidemia, występująca u 39 (58,21%) pacjentów, oraz nadwaga lub otyłość obserwowane u 25 (33,78%). Częstość występowania innych zaburzeń kształtowała się następująco: zaburzenia w stężeniu hormonów płciowych występowały u 14 (27,45%) pacjentów, nieprawidłowy poziom PTH u 13 (19,4%), nieprawidłowe stężenie IGF-1 u 9 (14,75%), niedobór wysokości u 9 (12,16%), niedobór masy ciała u 8 (11,11%), niedoczynność tarczycy u 7 (9,72%), obniżone BMD u 6 (8,69%), nadczynność tarczycy u 2 (2,78%). Wnioski. Pacjenci po leczeniu przeciwnowotworowym są w istotnym stopniu narażeni na zaburzenia endokrynologiczne. Wymagają oni szczegółowych badań kontrolnych w celu wykrycia nieprawidłowości oraz wdrożenia odpowiedniego leczenia. Warto zwrócić uwagę na częste występowanie więcej niż jednego zaburzenia u danego pacjenta.