Sindrom WAGR - prikaz slučaja

Congenital anomaly syndrome consisting of Wilms tumor, aniridia, genitourinary malformations and mental retardation (WAGR) is a rare, sporadic genetic disorder characterized by a de novo deletion in the distal band of llp13 chromosome. The syndrome is usually recognized by sporadic aniridia present at birth, often followed by the development of Wilms tumor in early childhood, but possible at any age. Genetic testing using fluorescence in situ hybridization (FISH) is the method of choice to detect specific deletions. The multidisciplinary approach in medical treatment not only of the tumor, but of a large variety of clinical features and possible complications is highly demanding and challenging. We report on a boy born with aniridia, cryptorchidism and facial dysmorphism recognized as WAGR syndrome in neonatal period, subsequently confirmed by genetic testing. Wilms tumor developed at the age of one year. Surgical treatment and chemotherapy resulted in complete remission for almost six years now. However, an increased risk of late post-treatment complications and development of de novo tumor in the contralateral kidney is a permanent threat. Therefore, ongoing oncologic follow up along with ophthalmologic and neurologic treatment and psychological support are a lifelong necessity.Sindrom WAGR je rijedak genetski poremećaj sporadične pojavnosti koji se klinički prezentira Wilmsovim tumorom, aniridijom, genitourinarnim anomalijama i mentalnom retardacijom. Obilježen je de novo delecijom u distalnom kraku 11. kromosoma u regiji 11 p13, a dokazuje se genetskim ispitivanjem metodom fluorescentne in situ hibridizacije (FISH). Sindrom se najčešće prepoznaje po aniridiji prisutnoj kod rođenja, dok se Wilmsov tumor obično razvija tijekom ranog djetinjstva, no moguće je u bilo kojoj životnoj dobi. Multidisciplinski pristup je nužan u liječenju ne samo tumora, nego i raznolikih kliničkih obilježja i mogućih komplikacija sindroma koji čine poseban terapijski izazov. Prikazujemo slučaj dječaka kod kojeg je sindrom WAGR prepoznat u novorođenačkoj dobi na temelju kliničkih obilježja (aniridija, facijalna dizmorfija, kriptorhizam), a potvrđen kasnijim genetičkim testiranjem. Unatoč redovitim kontrolama Wilmsov tumor je otkriven već u uznapredovalom stadiju u dobi od 14 mjeseci. Nakon provedenog kirurškog liječenja i kemoterapije uslijedila je potpuna remisija koja traje gotovo šest godina. Međutim, zbog rizika od kasnih poslijeterapijskih komplikacija te razvoja de novo tumora u preostalom, kontralateralom bubregu redovite onkološke kontrole su doživotna nužnost, kao i trajna oftalmološka, neurološka i psihološka skrb

Blizanci i neurorazvojni ishod: utjecaj medicinski potpomognute oplodnje, prijevremenog rođenja i restrikcije rasta

Nesrazmjer udjela blizanaca u općoj populaciji novorođenčadi u odnosu na udio u mortalitetu i morbiditetu ukazuje na njihovu posebnost. Neurološki morbiditet blizanaca usko je povezan s nepovoljnim čimbenicima i komplikacijama blizanačkih trudnoća kao što su diskordantni rast, monokorijalnost i prijevremeni porođaj. Premda su postupci medicinski potpomognute oplodnje značajno utjecali na porast incidencije blizanačkih trudnoća, nepovoljni utjecaj postupaka samih po sebi na neurološki ishod nije utvrđen. Dok se teže neurološke posljedice (prije svega cerebralna paraliza) mogu prepoznati u ranom djetinjstvu, neki blaži poremećaji (posebice kognitivni, emocionalni i intelektualni) manifestiraju se u kasnijem, predškolskom ili školskom uzrastu. Stoga je dugoročno praćenje blizanaca neophodno za cjelovitu procjenu njihovog neurorazvojnog ishoda

Thromboprophylaxis in pregnant patient-specific risks

Background: Pregnancy and the puerperium are well-established risk factors for venous thromboembolism. Prothrombotic changes start after conception and normal coagulation returns eight weeks after the labour. The risk of DVT is approximately twice as high after caesarean delivery than vaginal birth. Specific risks: Inherited or acquired thrombophilias increase thromboembolic risk and influence the approach to thromboprophylaxis. Additional factors that increase thrombotic risk include immobilisation, such as bed rest for pregnancy complications, surgery including caesarean section, ovarian hyperstimulation during gonadotropin use for in vitro fertilisation, trauma and malignancy. The preferred agents for thromboprophylaxis in pregnancy are heparin compounds; these agents do not cross the placenta and therefore appears safe for the fetus. Because of the theoretical risk of epidural spinal haemorrhage in women receiving heparin that undergo epidural or spinal anaesthesia many anaesthesiologist will not perform neuraxial regional anaesthesia in women who have recently received heparin. Anaesthesia guidelines advise waiting to insert the needle at least 10 to 12 hours after the last prophylactic dose of LMWH, and at least 24 hours after the last therapeutic dose. Conclusion: Despite the increased risk of thrombosis in pregnancy, anticoagulants are not routinely indicated, because the risks usually outweigh the benefits. The exception is women on life-long anticoagulation or women with history of thrombosis or thrombophylia.Heparin therapy must be interrupted temporarily during the immediate peripartum interval to minimise the risk of haemorrhage and to allow for the option of regional anaesthesia

ADRENAL CRISIS IN FEMALE NEWBORN WITH UNRECOGNIZED CONGENITAL ADRENAL HYPERPLASIA – CASE REPORT

Sažetak. Kongenitalna adrenalna hiperplazija (KAH) zbog deficita 21-hidroksilaze je najčešći uzrok dvosmislenog spolovila u ženske novorođenčadi. Nedostatak ovog enzima dovodi do poremetnje biosinteze kortizola u kori nadbubrežne žlijezde i ekscesivne produkcije adrenalnih androgena s posljedičnom virilizacijom ženskih fetusa. U klasičnom obliku bolest se javlja pojavnošću od 1:10000–15000 živorođenih. Kod ¾ oboljelih postoji i poremećaj biosinteze aldosterona, uslijed kojeg se javljaju potencijalno letalne krize gubitka soli u prvim tjednima života. Prikazujemo slučaj neprepoznate virilizacije ženskog novorođenčeta koje je hospitalizirano u adrenalnoj krizi dvanaestog dana života. Nadoknada glu-kokortikoida (hidrokortizon), te mineralokortikoida (fludrokortizon) uz dodatak soli dovela je do brzog oporavka i zadovoljavajuće kontrole bolesti tijekom 40 dana hospitalizacije. Djevojčica je otpuštena kući s dobrom prognozom za budući rast i razvoj uz preporuku trajne nadoknadne terapije pod kontrolom endokrinologa.Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most frequent cause of genital ambiguity in female newborns. Enzyme deficiency causes a disorder of cortisol synthesis by the adrenal cortex and leads to excessive androgen production resulting in subsequent genital virilization of female fetuses. The incidence of the classical form is 1:10000–15000 live births. About ¾ of affected infants also suffer from a disorder of aldosterone biosynthesis, which can lead to potentially lethal salt-losing crises within the first weeks of life. Here, we report of the case of an unrecognized virilization of a female newborn, who was hospitalized after an adrenal crisis at the twelfth day of life. Supplementary glucocorticoid (hydrocortisone) and mineralocorticoid (fludrocortisone) treatment with the addition of salt led to a fast recovery and satisfactory control of disease during 40 days of hospitalization. The girl was released from the hospital with good prognosis for the future growth and develompent with the recommended ongoing supplementary treatment under the supervision of an endocrinologist

ADRENAL CRISIS IN FEMALE NEWBORN WITH UNRECOGNIZED CONGENITAL ADRENAL HYPERPLASIA – CASE REPORT

Sažetak. Kongenitalna adrenalna hiperplazija (KAH) zbog deficita 21-hidroksilaze je najčešći uzrok dvosmislenog spolovila u ženske novorođenčadi. Nedostatak ovog enzima dovodi do poremetnje biosinteze kortizola u kori nadbubrežne žlijezde i ekscesivne produkcije adrenalnih androgena s posljedičnom virilizacijom ženskih fetusa. U klasičnom obliku bolest se javlja pojavnošću od 1:10000–15000 živorođenih. Kod ¾ oboljelih postoji i poremećaj biosinteze aldosterona, uslijed kojeg se javljaju potencijalno letalne krize gubitka soli u prvim tjednima života. Prikazujemo slučaj neprepoznate virilizacije ženskog novorođenčeta koje je hospitalizirano u adrenalnoj krizi dvanaestog dana života. Nadoknada glu-kokortikoida (hidrokortizon), te mineralokortikoida (fludrokortizon) uz dodatak soli dovela je do brzog oporavka i zadovoljavajuće kontrole bolesti tijekom 40 dana hospitalizacije. Djevojčica je otpuštena kući s dobrom prognozom za budući rast i razvoj uz preporuku trajne nadoknadne terapije pod kontrolom endokrinologa.Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most frequent cause of genital ambiguity in female newborns. Enzyme deficiency causes a disorder of cortisol synthesis by the adrenal cortex and leads to excessive androgen production resulting in subsequent genital virilization of female fetuses. The incidence of the classical form is 1:10000–15000 live births. About ¾ of affected infants also suffer from a disorder of aldosterone biosynthesis, which can lead to potentially lethal salt-losing crises within the first weeks of life. Here, we report of the case of an unrecognized virilization of a female newborn, who was hospitalized after an adrenal crisis at the twelfth day of life. Supplementary glucocorticoid (hydrocortisone) and mineralocorticoid (fludrocortisone) treatment with the addition of salt led to a fast recovery and satisfactory control of disease during 40 days of hospitalization. The girl was released from the hospital with good prognosis for the future growth and develompent with the recommended ongoing supplementary treatment under the supervision of an endocrinologist

THE IMPACT OF HYPOGLYCEMIA AND EPA AND DHA SUPPLEMENTATION ON BRAIN-DERIVED NEUROTROPHIC FACTOR LEVEL IN PREGNANT WOMEN WITH TYPE 1 DIABETES: A PROSPECTIVE COHORT STUDY

Background: In addition to its neuroprotective effect, Brain-derived neurotrophic factor (BDNF) also plays a role in glucose and lipid metabolism. This study aims: a) to find changes in the BDNF concentration during pregnancy in type 1 diabetes. b) to prove the effect of DHA and EPA supplementation on changes in BDNF concentrations c) to investigate the impact of hypoglycemia on BDNF concentration. Subjects and methods: The data from this study were from the PRE-HYPO cohort study. Twenty-one of them were on a standard diabetic diet enriched with EPA and DHA (EPA 120 mg/day and DHA 616 mg/day; Exposed group), and nineteen pregnant diabetic women were on the standard diabetic diet without EPA and DHA supplementation (Non-exposed group). In the first trimester of pregnancy, fift .9 mmol/L; HYPO+ group), and twenty-five pregnant women did not have hypoglycemia episodes (HYPO- group). Results: BDNF concentration significantly decreased during pregnancy from the first to the third trimester, in Non-exposed from 25.1 (22.0-30.2) to 22.1 (16.3-28.2), P<0.05, in the Exposed group from 22.1 (19.8-25.9) to 18.1 (14.8-18.9), P<0.01. Pregnant patients with hypoglycemia episodes (HYPO+ subgroup) had significantly higher BDNF in the third trimester of pregnancy [22.5 (20.6-28.4)] when compared with patients who did not develop hypoglycemia [16.3 (14.3-18.8), P<0.001]. In the third trimester of pregnancy, BDNF and n-6 PUFAs were associated with hypoglycemia (OR 1.818 95 % CI 1.079-3.003, P=0.025; OR 1.103 95 % CI 1.001-1.217, P=0.048). Total F.A.s were inversely associated with hypoglycemia (OR 0.969 95% CI 0.939-0.998, P=0.048). Conclusion: Pregnant women with hypoglycemia (HYPO+ group) had higher concentrations of BDNF in the first and third trimesters of pregnancy compared to those without hypoglycemia. An increase in body weight during pregnancy leads to a decrease in BDNF concentration

Appendicitis within inguinal hernia – case report of a premature newborn with Amyand’s hernia

Upala crvuljka unutar preponske kile ekstremno je rijetka pojava u nedonoščadi s procijenjenom incidencijom od oko 0,08-0,13%. Dijagnoza ovog izuzetnog entiteta, nazvanog Amyandova kila prema autoru koji ga je prvi opisao, najčešće je slučajna i obično se postavlja tek operativnim zahvatom. U prikazanog muškog nedonoščeta rođenog u 28. tjednu gestacije znaci ukliještenja desnostrane preponske kile javili su se tridesetog dana života. Kirurški zahvat je bio i dijagnostička i terapijska metoda. Nalazom neperforiranog, gangrenozno promijenjenog crvuljka unutar preponske kile postavljena je dijagnoza Amyandove kile. Nakon operativnog zahvata i uz dugotrajno antibiotsko liječenje uslijedio je potpuni oporavak. Prikaz bolesnika je podsjetnik na to da unatoč rijetkoj pojavnosti na Amyandovu kilu treba pomisliti u diferencijalnoj dijagnozi ukliještene desnostrane preponske kile u nedonoščadi.Acute appendicitis within an inguinal hernia is an extremely rare condition among premature newborns with estimated incidence ranging from 0.08% to 0.13%. The diagnosis of this extraordinary entity, known as Amyand’s hernia according to the author who fi rst described it, is often accidental and usually established intraoperatively. We report a case of a boy born at 28 weeks of gestation, who presented with incarcerated right inguinal hernia on his thirty day of life. Surgical intervention was both a diagnostic and therapeutic procedure. Intraoperative diagnosis of Amyand’s hernia was established based on the fi nding of non-perforated, gangrenous appendicitis within the inguinal hernial sac. Appendectomy and hernia repair followed by long-term antibiotic treatment led to complete infant’s recovery. This case report reminds that regardless of its rarity, clinicians should be aware of Amyand’s hernia in the evaluation of incarcerated right side inguinal hernia in preterm newborns

THE IMPACT OF HYPOGLYCEMIA AND EPA AND DHA SUPPLEMENTATION ON BRAIN-DERIVED NEUROTROPHIC FACTOR LEVEL IN PREGNANT WOMEN WITH TYPE 1 DIABETES: A PROSPECTIVE COHORT STUDY

Background: In addition to its neuroprotective effect, Brain-derived neurotrophic factor (BDNF) also plays a role in glucose and lipid metabolism. This study aims: a) to find changes in the BDNF concentration during pregnancy in type 1 diabetes. b) to prove the effect of DHA and EPA supplementation on changes in BDNF concentrations c) to investigate the impact of hypoglycemia on BDNF concentration. Subjects and methods: The data from this study were from the PRE-HYPO cohort study. Twenty-one of them were on a standard diabetic diet enriched with EPA and DHA (EPA 120 mg/day and DHA 616 mg/day; Exposed group), and nineteen pregnant diabetic women were on the standard diabetic diet without EPA and DHA supplementation (Non-exposed group). In the first trimester of pregnancy, fift .9 mmol/L; HYPO+ group), and twenty-five pregnant women did not have hypoglycemia episodes (HYPO- group). Results: BDNF concentration significantly decreased during pregnancy from the first to the third trimester, in Non-exposed from 25.1 (22.0-30.2) to 22.1 (16.3-28.2), P<0.05, in the Exposed group from 22.1 (19.8-25.9) to 18.1 (14.8-18.9), P<0.01. Pregnant patients with hypoglycemia episodes (HYPO+ subgroup) had significantly higher BDNF in the third trimester of pregnancy [22.5 (20.6-28.4)] when compared with patients who did not develop hypoglycemia [16.3 (14.3-18.8), P<0.001]. In the third trimester of pregnancy, BDNF and n-6 PUFAs were associated with hypoglycemia (OR 1.818 95 % CI 1.079-3.003, P=0.025; OR 1.103 95 % CI 1.001-1.217, P=0.048). Total F.A.s were inversely associated with hypoglycemia (OR 0.969 95% CI 0.939-0.998, P=0.048). Conclusion: Pregnant women with hypoglycemia (HYPO+ group) had higher concentrations of BDNF in the first and third trimesters of pregnancy compared to those without hypoglycemia. An increase in body weight during pregnancy leads to a decrease in BDNF concentration

SEVERE HEMOLYTIC DISEASE IN A NEWBORN CAUSED BY ANTI-K ANTIBODIES

Hemolitička bolest novorođenčeta (HBN) posljedica je majčine aloimunizacije na eritrocitne antigene fetusa. Majčina protutijela IgG razreda kroz posteljicu prelaze u fetalnu cirkulaciju te vezanjem za površinske eritrocitne antigene uzrokuju njihovo razaranje. U najtežim slučajevima razvija se hidrops fetusa, a najčešće hiperbilirubinemija i anemija novorođenčeta. Učestalost anti-K protutijela kao uzroka HBN-a slijedi odmah iza anti-D protutijela. Tijekom 80-ih godina prošlog stoljeća uočen je različiti mehanizam djelovanja anti-D i anti-K protutijela. HBN uzrokovana anti-K protutijelima je pretežno posljedica supresije eritropoeze, a hemoliza fetalnih eritrocita je manje izražena. HBN se može javiti i u prvoj trudnoći. U slučaju koji prikazujemo Kell negativna majka se imunizirala trudnoćom s Kell pozitivnim djetetom, što je dovelo do teške anemije novorođenčeta. Nalaz anti-K protutijela u majčinom serumu i na djetetovim eritrocitima, uz odgovarajući Kell fenotip oca, potvrdili su dijagnozu. Zahvaljujući pravodobnom i adekvatnom tretmanu transfuzijama, djevojčica je imala potpuni i brzi oporavak, bez posljedica za rast i razvoj.Hemolytic disease of the newborn (HDN) is a consequence of the mother\u27s alloimmunization towards fetal erythrocyte antigens. Maternal IgG class antibodies cross the placenta into the fetal circulation and attach to the antigenic sites on the surface of the erythrocytes, hence destroying them. Hydrops fetalis is the most severe form of the disease, but hyperbilirubinemia and anemia are more common. The incidence of HDN caused by anti-K antibodies comes immediately after the incidence of HDN caused by anti-D antibodies. During the 1980\u27s a different mechanism was noted for anti-D and anti-K antibodies. Suppression of erythropoesis, rather than hemolysis, is the predominant mechanism in HDN related to Kell aloimmunization, and may occur during the first pregnancy. In our case, the aloimmunization of the K-negative mother occured during pregnancy with a K-positive fetus, leading to severe anemia in the newborn. Serological findings of anti-K antibodies in the mother\u27s serum, and the presence of Kell antigens on the surface of the child\u27s erythrocytes, compiled with the father\u27s Kell antigen status established the diagnosis. Due to timely and adequate treatment with transfusions , the girl recovered completely without consequences to growth and development

THE IMPORTANCE OF ANTENATAL IMMUNOPROPHYLAXIS FOR PREVENTION OF HEMOLYTIC DISEASE OF THE FETUS AND NEWBORN

Hemolitička bolest fetusa i novorođenčeta (HBFN) je posljedica majčine aloimunizacije na eritrocitne antigene fetusa. Aloimunizacija na D antigen iz Rhesus (Rh) sustava krvnih grupa ima posebno značenje budući da se radi o najjačem eritrocitnom imunogenu. Otkako se unatrag četiri desetljeća rutinski provodi postnatalna profilaksa imunizacije davanjem anti-RhD imunoglobulina RhD negativnim ženama, drastično je smanjen mortalitet zbog HBFN. Uvođenjem antenatalne profilakse klinički značajna HBFN je postala izuzetno rijetka. Sporadični teški oblici bolesti su uglavnom posljedica nedosljednosti u provođenju profilakse. U slučaju koji opisujemo nije prepoznat rizik imunizacije tijekom prve majčine trudnoće, te je izostala antenatalna prevencija. Nakon primarne imunizacije, u drugoj je trudnoći s RhD pozitivnim djetetom došlo do žestokog sekundarnog imunološkog odgovora majke i ranog razvoja teške fetalne anemije. Intrauterine transfuzije su spasile vitalno ugroženi fetus, ali su istodobno uzrokovale snažnu eritroidnu supresiju. Anemija koja je trajala mjesecima nakon rođenja liječena je ponavljanim transfuzijama, te humanim rekombinantnim eritropoetinom. Unatoč teškoj kliničkoj slici, kratkoročni ishod bolesti je povoljan i dječak zasada ima uredan rast i razvoj. Ipak, rizici kasnih posljedica, a posebice neurorazvojnih odstupanja nalažu daljnje pomno praćenje djeteta. Opisani slučaj ukazuje na trajnu aktualnost problematike Rh imunizacije u nas. Provođenje antenatalne imunoprofilakse je prvi i ključni korak u kvalitetnoj prevenciji HBFN.Hemolytic disease of the fetus and newborn (HDFN) is a consequence of maternal alloimmunization against fetal red blood cell antigens. Alloimmunization against D antigen from Rhesus (Rh) blood group system is particularly important because of its strong immunogenicity. During the last few decades, the introduction of RhD prophylaxis by postpartum administration of anti-D immunoglobulin to RhD negative women, now improved with antenatal prophylaxis, has led to a dramatic decrease in perinatal mortality and morbidity from HDFN. However, severe cases have not disappeared, mostly due to prophylaxis failure. In our case, inappropriate prenatal care during the first pregnancy in an RhD negative mother resulted in primary immunization. In the next pregnancy with an RhD positive child, the mother’s secondary immune response was extremely strong and led to early development of severe fetal anemia. The fetus survived thanks to the treatment with intrauterine transfusions (IUT), but they caused suppression of erythropoiesis, which lasted for months after birth. The long lasting, late anemia was treated with repeated postnatal red cell transfusions and recombinant human erythropoietin (rHuEPO). Despite the severity of HDFN in our case, the short-term outcome is good. The boy has normal growth until now, but due to the possibility of an adverse long-term neurodevelopmental outcome, this case requires continuous follow up. It also reminds of the fact that RhD alloimmunization remains an actual problem in daily routine. Antenatal prophylaxis is a crucial step in quality care of those who are at a risk of HDFN