Hashimoto Thyroiditis in Childhood -Review of the Epidemiology, Genetic Susceptibility and Clinical Aspects of the Disease

Abstract Chronic autoimmune thyroiditis or Hashimoto's thyroiditis (HT) is the most common cause of thyroid diseases in children and adolescents. It is also the most common cause of acquired hypothyroidism with or without goiter. The incidence of autoimmune thyroiditis has increased dramatically over the past few decades, affecting up to 5% of the general population in iodine sufficient areas. HT is caused by the complex interplay of genetic, environmental, and endogenous factors. Significant progress has been made in identifying and characterizing the genes involved in pathogenesis of the disease. The aim of this review is to analyze current opinions and options regarding the etiology, genetic contribution to the pathogenesis, evaluation, diagnosis, treatment, and prognosis of the HT in children

Фацијална пареза кај новороденче: Приказ на случај

Unilateral congenital facial palsy in the newborn occurs more often as isolated than in the context of syndromes or developmental defects. Recognition of the etiological factor, the severity of the clinical presentation, the dynamics of recovery are a guide for a multidisciplinary approach, a range of investigations and treatment. In a non-therapeutic approach, unsupported by sufficiently reliable data from the literature, there is a dilemma whether and how long one has to wait and observe the improvement of clinical results, before determining the range of examinations in the newborn. In facial paresis of prenatal or perinatal origin, identical to non-congenital Bell's palsy, infectious and anatomical-structural causes should initially be excluded. This paper presents a case of a symmetrical hypotrophic premature infant with a manifestation of acute Bell's palsy at birth, with negative biomarkers for infectious etiology and a normal brain ultrasound. The newborn underwent a special neonatal care with targeted local treatment. Towards the end of the first postnatal week, there was an evident withdrawal of clinical symptomatology.  Еднострана вродена парализа на лицето кај новороденчето почесто се јавува изолирано, одошто во склоп на синдроми или од дефект во развојот. Препознавањето на етиолошкиот фактор, тежината на клиничката презентација, динамиката на опоравувањето ќе бидат смерница за мултидисциплинарен пристап, палета на иследувања и третман. При вонтерапевтски приод, непоткрепен со доволно сигурни податоци од литературата, постои дилема дали и колку да се чека и обсервира подобрувањето на клиничките резултати, пред да се одреди палетата на иследувања кај новороденото дете. Кај фацијалната пареза од пренатално или перинатално потекло, идентично како кај неконгениталната парализа на Бел, првично треба да се исклучат инфективни и анатомско-структурни причини. Во овој труд се презентира случај на симетрично  хипотрофично прематурно новороденче со манифестација на акутна парализа на Бел на раѓање, со негативни биомаркери за инфективна етиологија и уреден ултрасонографски наод на мозочните структури. Новороденото дете беше на специјална неонатална нега со целно спроведуван локален третман. Кон крајот на првата постнатална седмица покажа евидентно повлекување на клиничката симптоматологија. &nbsp

Genetics of Gland- in-situ or Hypoplastic Congenital Hypothyroidism in Macedonia

Neonatal screening in Macedonia detects congenital hypothyroidism (CH) with an incidence of 1 in 1,585, and more than 50% of cases exhibit a normally located gland-in-situ (GIS). Monogenic mutations causing dyshormonogenesis may underlie GIS CH; additionally, a small proportion of thyroid hypoplasia has a monogenic cause, such as TSHR and PAX8 defects. The genetic architecture of Macedonian CH cases has not previously been studied. We recruited screening-detected, non-syndromic GIS CH or thyroid hypoplasia cases (n = 40) exhibiting a spectrum of biochemical thyroid dysfunction ranging from severe permanent to mild transient CH and including 11 familial cases. Cases were born at term, with birth weight >3,000 g, and thyroid morphologies included goiter (n = 11), thyroid hypoplasia (n = 6), and apparently normal-sized thyroid. A comprehensive, phenotype-driven, Sanger sequencing approach was used to identify genetic mutations underlying CH, by sequentially screening known dyshormonogenesis-associated genes and TSHR in GIS cases and TSHR and PAX8 in cases with thyroid hypoplasia. Potentially pathogenic variants were identified in 14 cases, of which four were definitively causative; we also detected digenic variants in three cases. Seventeen variants (nine novel) were identified in TPO (n = 4), TG (n = 3), TSHR (n = 4), DUOX2 (n = 4), and PAX8 (n = 2). No mutations were detected in DUOXA2, NIS, IYD, and SLC26A7. The relatively low mutation frequency suggests that factors other than recognized monogenic causes (oligogenic variants, environmental factors, or novel genes) may contribute to GIS CH in this region. Future non–hypothesis-driven, next-generation sequencing studies are required to confirm these findings

Neonatal Hyperbilirubinemia in Newborns of the Republic of North Macedonia

Neonatal indirect hyperbilirubinemia is one of the most frequent neonatal problems that affect almost two thirds of term infants. Although etiology of jaundice has been widely studied, identification of pathological causes presents constant clinical challenge. Our study group performed an extensive retrospective study of etiology of neonatal hyperbilirubinemia and showed high frequency (44.37%) of jaundice of undefined etiology. The group included exaggerated physiological jaundice, early- and late-onset breast-milk jaundice, and no identifiable etiology. Other etiologies were neonatal infection, prematurity, birth trauma, and hemolysis represented with 15%. We described hematological parameters in both non-hemolytic and hemolytic type of jaundice; a significant correlation of relevant laboratory findings with etiology was established. In this chapter we will present our own data and perform a data-relevant literature review. Furthermore, investigation and management plan of neonatal indirect hyperbilirubinemia will be presented in accordance with own data and available literature

Vesicoureteral Reflux Detected with 99mTc-DTPA Renal Scintigraphy during Evaluation of Renal Function

BACKGROUND: Radionuclide techniques, as direct radionuclide cystography and 99mTc-DMSA scintigraphy, have been used in evaluation of vesicoureteral reflux (VUR) and reflux nephropathy (RN) in children. Dynamic 99mTc-DTPA scintigraphy is reserved for evaluation of differential renal function and obstruction in children, where hydronephrosis is detected by ultrasonography (US) pre- or postnatally. CASE REPORT: Six year old boy was prenatally diagnosed with bilateral hydronephrosis. Postnatal, severe bilateral VUR was detected by voiding urethrocytography. US and 99mTc-DTPA scintigraphy performed in the first month of life showed small left kidney that participated with 2% in the global renal function. Bilateral cutaneous ureterostomy has been performed in order to obtain good renal drainage and promote optimal renal growth. Twelve months later, classic antireflux procedure was done. Control 99mTc-DTPA scintigraphy, 5 ys after antireflux surgery, revealed persisting radioactivity during the diuretic phase, in the left kidney that indicated antireflux procedure failure with VUR reappearance. CONCLUSION: 99mTc-DTPA scintigraphy is the first method of choice for long-term monitoring of individual kidney function in children with VUR and other congenital urinary tract anomalies. Additionally, it can be used as indirect radionuclide cystography when rising of radioactivity in the kidney region, during the diuretic phase can indicate presence of VUR

Coagulopathy as initial manifestation of concomitant celiac disease and cystic fibrosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Celiac disease and cystic fibrosis have many common manifestations, such as malabsorption, steatorrhea and growth failure, and were for many years recognized as one clinical entity. Since their recognition as two separate diseases, their co-existence in a patient has been described sporadically; around 20 cases have been described in the literature. Taking into consideration the incidences of the two diseases, the chance of them occurring together is one in 2,000,000 in the general population.</p> <p>Case presentation</p> <p>We describe the case of a five-year-old boy of Turkish ethnicity with both celiac disease and cystic fibrosis, who presented initially with a skin hemorrhage. The diagnosis of celiac disease was made with a positive serum anti-tissue transglutaminase antibody test and the presence of HLA-DQ2 heterodimer, and confirmed on histology with small intestinal villous atrophy. A positive sweat test confirmed the diagnosis of associated cystic fibrosis.</p> <p>To the best of our knowledge there has been no previous report of this rare presentation of associated celiac disease and cystic fibrosis.</p> <p>Conclusion</p> <p>The clinical significance of this case is the consideration of malabsorption with both celiac disease and cystic fibrosis in patients who present with unexplained coagulopathy.</p

Genetics of Gland- in-situ or Hypoplastic Congenital Hypothyroidism in Macedonia

Neonatal screening in Macedonia detects congenital hypothyroidism (CH) with an incidence of 1 in 1,585, and more than 50% of cases exhibit a normally located gland-in-situ (GIS). Monogenic mutations causing dyshormonogenesis may underlie GIS CH; additionally, a small proportion of thyroid hypoplasia has a monogenic cause, such as TSHR and PAX8 defects. The genetic architecture of Macedonian CH cases has not previously been studied. We recruited screening-detected, non-syndromic GIS CH or thyroid hypoplasia cases (n = 40) exhibiting a spectrum of biochemical thyroid dysfunction ranging from severe permanent to mild transient CH and including 11 familial cases. Cases were born at term, with birth weight >3,000 g, and thyroid morphologies included goiter (n = 11), thyroid hypoplasia (n = 6), and apparently normal-sized thyroid. A comprehensive, phenotype-driven, Sanger sequencing approach was used to identify genetic mutations underlying CH, by sequentially screening known dyshormonogenesis-associated genes and TSHR in GIS cases and TSHR and PAX8 in cases with thyroid hypoplasia. Potentially pathogenic variants were identified in 14 cases, of which four were definitively causative; we also detected digenic variants in three cases. Seventeen variants (nine novel) were identified in TPO (n = 4), TG (n = 3), TSHR (n = 4), DUOX2 (n = 4), and PAX8 (n = 2). No mutations were detected in DUOXA2, NIS, IYD, and SLC26A7. The relatively low mutation frequency suggests that factors other than recognized monogenic causes (oligogenic variants, environmental factors, or novel genes) may contribute to GIS CH in this region. Future non–hypothesis-driven, next-generation sequencing studies are required to confirm these findings

First Macedonian child with tyrosinemia type 1 successfully treated with nitisinone and report of a novel mutation in the FAH gene

Introduction. Hereditary tyrosinemia type 1 (HT1) is a severe hereditary metabolic disorder of tyrosine metabolism due to fumarylacetoacetate hydrolase (FAH) deficiency and accumulation of toxic products in tissues. More than 80 mutations in the FAH gene are presently reported on the Human Genome Mutation Database. To date, no molecular genetic defects of HT1 in Macedonia have been described. Case outline. A female infant two and a half months old presented with failure to thrive, anemia, edemas, and severe coagulation disturbances. The diagnosis of HT1 was based on high levels of serum α-fetoprotein, increased serum tyrosine, and positive succinylacetone in urine. Nitisinone treatment with tyrosine-restriction diet was immediately introduced. The patient, currently aged five years, has normal growth, psychomotor development, and no focal lesions on abdominal MRI. A screening of the FAH gene revealed two heterozygous mutations – c.[1A>G];[784T>A]. The mutation c.784T>A is a novel one (p.Trp262Arg), and was predicted to be the cause of the disease by an in silico analysis. Conclusion. To date, this case is the first and only child with HT1 successfully treated with nitisinone in our country. Also, this is the first report of an HT1 patient caused by the c.784T>A mutation