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Cerebellar ataxia, mental retardation, and disequilibrium syndrome (CAMRQ) is a genetically and clinically heterogeneous disorder with four described subtypes. Autosomal recessive syndrome of cerebellar ataxia, mental retardation, and disequilibrium type 4 (CAMRQ4) is caused by mutations in the ATP8A2 gene. We report an 8-year-old boy with choreoathetosis, hypotonia, without the ability to keep his head up and profound mental retardation. There was quadrupedal locomotion, as well. MRI of the brain revealed a hypotrophy of the corpus callosum, diffuse white matter reduction, widespread delayed myelination and ventriculomegaly. Trio whole-exome sequencing revealed compound heterozygosity in the ATP8A2 gene consisting of a known variant c.1756C>T (p.Arg586*) inherited from the mother and a novel variant c.691_701delCTGATGAAGTT (p.Leu231fs) inherited from the father. CAMRQ type 4 has been found in about 50 patients. To the best of our knowledge, this is the first reported patient with CAMRQ4 with these gene variants. The clinical presentation is severe. [ABSTRACT FROM AUTHOR]

Introduction: Insulin induced edema (IIE) is a rare condition, usually found in newly diagnosed diabetes patients, either after insulin treatment initiation or after dose increment. It is a self-limited process, rarely associated with serosal effusions. Teenage girls with type 1 diabetes (T1DM) are most commonly affected. Patient and Methods: A 12-year-old girl was diagnosed with ketoacidosis (DKA). Seven days after initiation of the insulin treatment, at a stable total daily dose of insulin (TDDI) of 0.55 IU/kg, she came with two kilograms weight gain in only two days and edema of the feet and calves. Ultrasound of the heart found a 7 mm pericardial effusion. The diagnostic workout included clinical examination, biochemical, hormonal, allergen analyses and imaging which excluded other known causes of swelling. Conclusions: We describe an adolescent girl with newly diagnosed T1DM and a rare association of peripheral insulin-induced edema and pericardial effusion. Short-term diuretic treatment and salt restriction resolved this rare complication of insulin treatment. [ABSTRACT FROM AUTHOR]

Alström syndrome (ALMS) is an autosomal recessive disorder characterized by multiple organ involvement, including progressive cone-rod dystrophy, sensorineural hearing loss, childhood obesity, and type 2 diabetes mellitus. Pathogenic variants in the ALMS1 gene are the known cause for the occurrence of this devastating condition. Here we report on a 12 year old boy referred to the University Clinic with early signs of impaired hearing and vision, obesity, and scoliosis. Central vision was first affected, followed by peripheral vision. In addition, his weight began increasing after the age of two years, reaching 78 kg at a height of 157 cm (BMI 31.64). No polydactyly was present. His mental development was normal in spite of his hearing and vision impairments. There was acanthosis nigricans on the neck. ECG and the cardiac ultrasound were normal. At the age of 12 years, his testicles are 12 ml and his pubertal status is P2 A2. OGTT revealed impaired glucose tolerance with elevated insulin concentrations 121ulU/mL (reference range 2,00-29,1 ulU/mL). Renal function was unaffected, liver functions were normal. Uric acid and lipids were within normal plasma concentrations. A Whole Exome Sequencing was performed and a homozygous ALMS1 pathogenic, frameshift gene variant (LRG_741t1(ALMS1):c.4156dup; p.Thr1386AsnfsTer15) was determined as the cause of the disease. Both parents were carriers for the variant. The absence of mental retardation and polydactyly differentiates Alström and Bardet-Biedle syndrome. [ABSTRACT FROM AUTHOR]

Copyright of Contributions / Prilozi (1857-9345) is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Contributions / Prilozi (1857-9345) is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Obesity is the most common chronic metabolic disease in children and adolescents. It has reached epidemic ranges and is a significant global problem. Objective: This study aimed to investigate the possible metabolic disturbances in children and adolescents with obesity and severe obesity. Subjects and methods: This cross-sectional study included 158 (82 boys, 76 girls) obese children and adolescents between ages of 0 and 17years (10.43 ± 3.11 years). The obesity was defined according to the sex- and age-specific growth charts proposed by the Centers for Disease Control and Prevention as BMI ≥ 95th percentile. Severe obesity was classified as 120% of the 95th percentile for age and sex. Study participants underwent medical assessment and analysis of: ALT, AST, fasting serum triglycerides, total serum cholesterol, fasting plasma glucose and plasma glucose from oral glucose tolerance test. Results: The majority of study participants were severely obese (69.92%). The highest distribution of abnormal biochemical results was seen in elevated ALT (53.91%) followed by elevated triglycerides (34.75%). The prevalence of abnormal total cholesterol level was significantly higher (p=0.04) in the group of obese children compared to the severely obese children. The levels of total cholesterol were also statistically higher in the group of adolescents compared to preadolescents (p=0.02). An important number of obese patients (2.5%) and even higher number of severely obese patients (5.26%) had carbohydrate intolerance. Conclusion: There was a significant elevation of ALT, total serum cholesterol and triglycerides in all study participants. High serum lipids and high hepatic enzymes (as introduction in non-alcoholic fatty liver disease) are alarming. Strikingly, there was carbohydrate intolerance in an important number of patients. Treatment and education of patients and parents is mandatory. Preventive measures in the society concerning childhood obesity are necessary. [ABSTRACT FROM AUTHOR]

Introduction: Children born small for gestational age (SGA) have increased prevalence of metabolic syndrome, diabetes mellitus type 2 (DM2), hypertension and cardiovascular and cerebrovascular events in adulthood. Patients and Methods: In 100 children born SGA, and in second cohort having 32 obese children born in term with normal birth weight and height, anthropometric measurements and biochemical metabolic profiles were analysed. The Homeostasis Model Assessment - Insulin Resistance and Sensitivity (HOMA-IR and IS) were calculated. Results: Four overweight/obese children (M:F=3:1) with normal height were found among 100 SGA children. The body mass index (BMI) in all 4 children was above the 98th percentile and the mean BMI z-score was (2.04±0.30 SDS). The HOMA-IR index in all four children was increased: 1.26-2.65 (>1). Two teenagers had significant hyperinsulinemia (198.00 uIU/ml and 275 uIU/ml) and were treated with metformin. Two girls needed only a diet and increased physical activity. The mean values of HOMA-IR (1.26-2.65; N< 1) and IS (58 ±17.12) in fo-ur SGA overweight/obese children who caught-up growth had indistinguishable values with the group of 32 (M: F=21:11) obese children (HOMA-IR 1.83±1.2 SDS; IS 82.99±64.53 SDS) born in term with normal birth weight and height. Conclusions: SGA born children are usually thin; nevertheless we found overweight and obesity in 4% of the patients. Two of those children have metabolic syndrome. Excess weight, obesity and metabolic syndrome in SGA children result with increase of their inherent risk for DM2, cardiovascular and cerebrovascular diseases in adulthood. [ABSTRACT FROM AUTHOR]

Copyright of Contributions / Prilozi (1857-9345) is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Contributions / Prilozi (1857-9345) is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The sixth SEE meeting on rare diseases (RDs) was held in MASA the November 10th, 2017. A block of lectures on rare renal diseases started the meeting: nephrotic syndrome, Alport syndrome, atypical HUS, hypophosphatemic rickets, CAKUT were presented in all complexities. Their molecular and genetic mechanisms were discussed. The discovery of a dozen of newly genes in CAKUT, congenital overgrowth, spodilocostal dysplasia, precocious puberty has been done with collaboration of Macedonian and foreign researchers. NGS and other molecular methods in diagnosis of RDs have been presented by several presenters. The mitochondrial diseases, the novelties and importance of early discovery were comprehensively presented and discussed. The genetics and treatment of persistent neonatal hypoglcaemia were of special interest. Dysmorphic syndromes (Klippel Feil) were also presented. A session of oral electronic posters was reach and inspiring. Several lectures dealt with mucopolisaccaridoses, glycogen storage diseases and the possibilities for their diagnosis and treatment. Enzyme replacement treatement (ERT), its availability, effects (or the lack of it on the brain), intratecal ERT administration and further prospects of eventual gene treatment were comprehensively exposed and discussed. The main purposes of this traditional meeting are hopefully fulfilled: increased number of patients with RDs treated and cutting edge presentations got. [ABSTRACT FROM AUTHOR]

Rare renal diseases (RRD) are an important category of rare disease (RD) as they can do great damage to the patients, families and society. The patient may undergo years even decades of numerous investigations including invasive procedures and yet not have definitive and precise diagnose and therefore, no opportunity for appropriate treatment. The great progress in molecular genetic techniques characterized many Mendelian diseases on molecular level. This gave the possibility for appropriate prevention and treatment interventions, genetic counseling and prenatal diagnosis. Herein, we summarize the current status of RRD in Macedonia. The research interest of Macedonian clinicians and scientists is focused on the genetics of congenital anomalies of the kidney and urinary tract (CAKUT), steroid resistant nephrotic syndrome, nephrolithiasis and nephrocalcinosis, cystic diseases and cilliopathies with collaborations with eminent laboratories in Unites States and Europe. This collaboration resulted in detection of new genes and pathophysiological pathways published in The New England Journal of Medicine and in other high impact journals. Macedonian health professionals have knowledge and equipment for diagnosis of RRD. Unfortunately the lack of finances is great obstacle for early and appropriate diagnosis. Participation in the international registries, studies and trials should be encouraged. This would result in significant benefit for the patients, health professionals and science. [ABSTRACT FROM AUTHOR]

Copyright of Contributions / Prilozi (1857-9345) is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Contributions / Prilozi (1857-9345) is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Congenital anomalies of the kidney and urinary tract (CAKUT) represent several types of malformations with occurrence of 1 in about 500 live births. Objective: Small for gestation age (SGA) may influence in prevalence of CAKUT and progression of chronic kidney disease (CKD) in children. The aim of this study was to elaborate our experiences with detected CAKUT in a cohort of SGA born children in Macedonia. Methods: Our cohort consisted of 100 SGA born children investigated for associated congenital anomalies of urinary tract. We analyzed anthropometric and clinical birth data in children with diagnosed CAKUT and estimated the stage and time of onset of CKD by biochemical and imaging technics. Results: We revealed 7 (7.0%) SGA born children with congenital anomalies of the urinary tract. Their mean birth weight was very low 1855 gr (-3.93 SDS) and the birth length 45.57cm (-2.17 SDS), as well. A significant growth failure with reduced weight and BMI were noticed at the time of diagnosis. A diagnosis of CAKUT in 4/7 was established in the first few months of life, but in others 3 later in early childhood. Three children revealed with unilateral kidney agenesis, 2 had hypo-dysplastic kidneys and in 2 children was found vesicoureteral reflux. Normal glomerular filtration rate was estimated in 2 children with CAKUT. Stage 2 CKD with GFR 60-90 ml/minx1.73m2 had 3 children, 1 patient was graded in stage 3 and one child needed kidney transplantation, stage 5 CKD. Conclusions: We presented 7 SGA born children with CAKUT. An early recognition, assessment and treatment of these anomalies might improve their quality of life. [ABSTRACT FROM AUTHOR]

Copyright of Contributions / Prilozi (1857-9345) is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Nephrotic syndrome is defined as the association of massive proteinuria, hypoalbuminaemia, edema, and hyperlipidemia. It is separated to steroid-sensitive or steroid-resistant (SRNS) forms in respect to the response to intensive steroid therapy. SRNS usually progresses to end-stage renal failure. According to the North American Pediatric Renal Trials and Collaborative Studies SRNS constitutes the second most frequent cause of ESRD in the first two decades of life. Unfortunately, there is no curative treatment for majority of patients. Majority of the SRNS patients have the histologic picture of focal segmental glomerulosclerosis. Interestingly, the risk of recurrence in the kidney graft in patients with hereditary SRNS is lower than in those who do not have genetic background. The etiology and pathogenesis of SRSN has remained enigma for decades. The discovery of 39 dominant or recessive SRNS genes enabled better understanding of the function of the glomerular podocytes and slit membrane. Hildebrandt′s group has shown that 85% of the SRNS cases with onset by 3 months of age and 66% with onset by 1 year of age can be explained by recessive mutations in one of four genes only (NPHS1, NPHS2, LAMB2, or WT1). The same group used modern diagnostic techniques such as the next generation sequencing and tested a large international cohort of SRNS patients (n = 1783 families). The diagnostic panel included 21 genes with a recessive mode of inheritance and 6 genes with a dominant mode of inheritance. Single-gene cause was detected in 29.5% (526 of 1783) of the families with SRNS that manifested before 25 years of age. The identification of causative single-gene mutations may have important therapeutic consequences in some cases. This is very important for patients who carry mutations in a gene of coenzyme Q10 biosynthesis (COQ2, COQ6, ADCK4, or PDSS2). In these patients the treatment with coenzyme Q10 may be indicated. Also, patients with recessive mutations in PLCE1 may respond fully to the treatment with steroids or cyclosporine A. The patients with CUBN may benefit the treatment with vitamin B12. The detection of causative mutations may also be very important for familial genetic counseling and for prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Diabetes mellitus type 1 (T1DM) is a chronic disease with long term consequences dictating daily struggle to maintain a good metabolic control. Children and adolescents with T1DM seem to have inferior psychological adjustment to their normal counterparts, which might be associated with glycemic control and disease duration. The aim of this study is to evaluate the psychological characteristics of children and adolescents with T1DM treated last year in the University Children Hospital in Skopje, Macedonia and to propose some response measures. For psychological evaluation we used CBCL (Child Behavior Check List), GAS (General Anxiety Scale), EPQ (Eysenck Personality Questionnaire) and MMPI-201 (Minnesota Multiphasic Personality Inventory). The results confirmed the following psychological characteristics: mild depression and anxiety, emotional instability, need for social acceptance, as well as the possible psychopathic traits. Suffering for a complex metabolic and chronic illness, these patients need psychological evaluation and intervention in the management. [ABSTRACT FROM AUTHOR]

The 4th meeting on rare diseases in South Eastern Europe (SEE) was held in Skopje, at the Macedonian Academy of Sciences and Arts (MASA) on the 14th of November 2015. The focuses were metabolic, rare brain diseases as well as the rare dysmorphic syndrome. The authors of the report are particularly keen on stating that one of the main goals of the meeting, namely to help the treatment of patients with rare disease has begun to bear fruits. The talk on an iminosugar-based pharmacological chaperone compound as a drug candidate for the treatment of GM1-gangliosidosis and mucopolysaccharidosis IVB (Morquio disease type B) was enlightening. To date, there is no treatment available to be offered to patients, but chaperones lead mutated proteins to adopt a native-like conformation and to successfully traffic to their normal cellular destination. DORPHAN is developing an iminosugar-based pharmacological chaperone compound for the treatment of GM1-gangliosidosis and mucopolysaccharidosis IVB. A talk on recent developments in the laboratory diagnosis of mucopolysaccharidoses (MPS) was particularly interesting, covering the laboratory diagnosis of the MPS diseases by a strategy of clinical examination, biochemical analysis of urine samples, enzyme tests and genetic characterization of underlying mutations. New techniques were developed, including analysis of urinary glycosaminoglycans with tandem mass spectrometry, miniaturized enzyme tests or novel synthetic substrates for enzyme assays using mass spectrometry detection of products using dried blood spots. Feasibility and cost-effectiveness of these methods in newborn screening programs have been demonstrated. Neuromuscular RDs, and especially familial amyloid polyneuropathy (FAP) were a topic of the Bulgarian colleagues. Diagnosis, screening and the role of microglia were also topics of particular interest. In summary, this year RD meeting was exciting and productive on a wide range of diseases and on a novel insights on diagnosis and treatment. New methods are expanding our capabilities for a fast and precise diagnosis. Novel knowledge offers better distinction on whom to treat with which medications (e.g. steroid dependent nephrotic syndrome). Novel diseases or variants are published (segmental overgrowth). The authors of the report are particularly keen on stating that one of the main goals of the meeting, namely to help the treatment of patients with rare disease has begun to bear fruits. Namely, the Health Fund of Macedonia for the first time treats the patients with Gaucher′s disease. We are hopeful that the number of patients treated for Gaucher′s disease and the number of treated patients with other treatable RDs diseases will continue to grow. [ABSTRACT FROM AUTHOR]

Background: Bardet-Biedl syndrome (BBS) is a multisystem genetic disorder characterized with central obesity, pigmentary retinopathy, polydactyly, mental retardation, and hypogenitalism. Renal abnormalities have been recognized as a cardinal feature of the disease with serious prognostic implication. The aim of this study was to analyze the renal status in children with BBS and to implement appropriate interventions in those with progressive course Patients and methods: The diagnosis of BBS was established on the basis of criteria proposed by Beales et al. (J Med Genet 1999). Imaging of the kidneys and urinary tract was performed with ultrasound study, Tc99m DMSA scan and a cystographic study. Twenty four hour urine collections were obtained for estimation of proteinuria and creatinine clearance. Blood pressure was monitored at clinical visits or as 24-hour ambulatory monitoring. Results: There were 4 children (2 males, 2 females). All four children displayed abnormal kidney ultrasound and Tc99m DMSA scan resembling dysplastic kidney(s). Two of them had overt proteinuria (glomerulo-tubular pattern). Three children had normal blood pressure and glomerular filtration rate (GFR): 107, 145 and 95 ml/min/1.73m², and the fourth had hypertension and progressive worsening of the GFR at 65 ml/min/1.73m². Conclusion: Children with BBS should undergo imaging studies of the kidneys and urinary tract at initial work up; in those with renal dysplasia proteinuria, GFR and blood pressure should be regularly monitored to slow down progression to terminal renal failure. [ABSTRACT FROM AUTHOR]

Multiple congenital anomalies and craniofacial dysmorphism are characterizing the so-called Emanuel or supernumerary der(22)t(11;22) syndrome (OMIM609029). Mental and developmental retardation are major clinical features. The der(22) may arise from a parental balanced t(11;22)(q23;q11.2) or can be created de novo. Here we present a 2 years old boy with normal prenatal history, cyanotic at delivery and with ear anomalies, a preauricular tag, high-arched palate and micrognathia. There were neither microcephaly, nor heart or kidney defects. Psychological and motor testing at the age of 2 years confirmed significant mental and developmental delay. In addition, the child had seizures and an abnormal electroencephalogram. Cytogenetic and molecular analyses revealed a karyotype 47,XY,+der(22)t(11;22)(q23;q11.2). As parents refused further tests it could not be determined if the der(22) arose de novo or was parentally derived. Overall the present report should alert physician to offer cytogenetic and/or molecular diagnostics in comparable cases. [ABSTRACT FROM AUTHOR]

The Macedonian Academy of Sciences and Arts (MASA), held a scientific workshop for journal editors in biomedicine: "Publishing integrity and good practices in editing in biomedicine" on April 25, 2014 in MASA, Skopje. The meeting looked into old problems and new situations in editing and publishing, with emphasis on the situation in developing countries. This global knowledge-based society is founded on the results obtained from scientific research. The data from basic research in developed countries contribute in a quite substantial manner to the newly added economic value. One of the main reasons for underdevelopment in South Eastern Europe (SEE) is certainly a low or non-existent contribution of scientific research in the newly added economic value. This has largely to do with the perception of the political elites which simply lack the insight on the crucial importance of science in development. In the long term this leads to societies in which there are distortions in the understanding of the most basic values. Academic publishing has experienced tremendous growth: so far there are at least 50 million scientific articles. Interestingly, publishing in developing countries has experienced a rate of growth higher than in developed countries. However, this is not the case with the Balkan countries. The meeting looked at some old and some newly emerging problems in editing and publishing. First, the high cost for universities and researchers to purchase journals adversely affects both publishing and editing. In developing countries the high cost of purchasing scientific literature is an almost insurmountable problem in spite of the fact that some publishing companies offer discounted fees. Open access journals in South Eastern European (SEE) countries are hardly achievable as this also incurs costs that have to be covered in some way or other. The peer review process has the fundamental difficulty that reviewers are in the situation of a Procrustean bed, tending to accept reports which support the reviewer's concepts of thinking and, like Procrustes, cutting everything else out. Authorship is often a contentious issue, as undeserved authors appear on the list of authors. Some principles are now a norm in academic publishing. This applies to the declaration of a conflict of interest, the consent of the patient and the approval of the Ethical Board of the institution. This global informational technological revolution has, unfortunately, led to largely widespread and increasingly sophisticated deviations: plagiarism, data fabrication and data falsification as forms of scientific misconduct. Those events are now more widespread than in the past. Luckily new tools to track them are much better than previously. The race for perfect publishing integrity and for the best good practices in editing in biomedicine is on. New and old challenges will be met. The benevolent and caring society, educated professionals and an enlightened public remain essential preconditions. The wealth of nations depends on R&D and consequently on academic publishing. [ABSTRACT FROM AUTHOR]

Septo-Optic Dysplasia (SOD) is a rare disorder with postulated genetic and environmental etiology. Whilst initially considered as a very rare disease (defined as incidence of approx. 1 in 50,000 births) recent data gave a reported incidence of 1 in 10,000, with equal sex distribution. The diagnosis of SOD is predominantly a clinical one, and made with the presence of two or more features of the classic triad: 1) hypopituitarism, 2) optic nerve hypoplasia, and 3) midline brain defects, typically absence or hypoplasia of the septum pellucidum and/or corpus callosum. Hypopituitarism ranges from isolated to multiple hormone deficits, with diabetes insipidus in a minority. The condition is heterogeneous and may also manifest additional brain defects. Although homozygous mutations in the homeobox gene HESX1 have been identified in SOD, these are uncommon and genetic diagnosis can be made in only < 1% of patients with autosomal recessive inheritance. Autosomal dominant inheritance has also been reported. SOX2, SOX3 and OTX2 mutations have also been identified in some forms of SOD. The aetiology of SOD is uncertain but viral infections, environmental teratogens and vascular or degenerative damage have been postulated to account for its sporadic occurrence. Other factors (endogenous or exogenous) include parental age, parity, smoking, alcohol and substance abuse, antenatal bleeding, and ethnicity. Cocaine abuse during pregnancy, which is a potent vasoconstrictor has recently been identified as a potential external cause. The phenotype of SOD is highly variable; the clinical picture may include visual impairment, short stature, obesity and sleep-wake inversion. Approximately 75-80% of patients exhibit optic nerve hypoplasia, which may be the first presenting feature. Pituitary insufficiency may evolve over time, and children with possible SOD must be kept under careful endocrine follow-up. Untreated hormonal abnormalities will further jeopardize neurodevelopment of children with SOD and could also lead to life-threatening adrenal crises. The attention should be focussed on early diagnosis and treatment and education of paediatricians how to recognize this complex disorder. [ABSTRACT FROM AUTHOR]

Background: The genetic background of idiopathic central precocious puberty (ICPP) is not well understood, and is thought to arise from the effect of multiple genes. Familial ICPP have been reported suggesting the existence of monogenic causes of ICPP. The neurokinin B (NKB) system has recently been implicated in the regulation of the human reproductive axis. In humans, NKB and its receptor are encoded by the TAC3 and TACR3 genes, respectively. Mutations in these genes have been suggested to be causative for ICPP. Methods: ICPP was defined by pubertal onset before 8 yrs of age in girls, and a pubertal LH response to GnRH testing. Twenty eight girls with ICPP were included in the study (age at diagnosis was 5.72 ± 2.59; bone age, 6.12 ± 2.81, height at the start of treatment, 0.90 ± 1.48 SD). LHRH test was performed and was pubertal in all subjects (LH 20.35 ± 32.37 mIU/ml; FSH 23.32 ± 15.72 mIU/ml). The coding regions of TAC and TACR3 were sequenced. Results: No rare variants were detected in TAC and TACR3 in the 28 subjects with ICPP. Conclusions: We confirmed that mutations in TAC and TACR3 are not a common cause for ICPP. [ABSTRACT FROM AUTHOR]

Pediatric kidney diseases were in the focus of the World Kidney Day 2016. Macedonian pediatric nephrologists gave their contribution with public appearance in kindergartens, primary and seconddary schools, with interactive lectures and discussion with the youngest about the kidney function, healthy life style and simple measures to prevent kidney and urinary tract diseases. Besides promotive appearance in the media, series of lectures were presented in front of the health professionals. The aim was to attract the attention of the professionals for early diagnosis and prevention of kidney disease. The action starts in utero, followed by early postnatal imaging and assessment, conservative treatment and in selected cases surgical treatment. The emphasis is on the multidisciplinary and comprehensive approach to children and adolescents with kidney diseases. [ABSTRACT FROM AUTHOR]

Krabbe disease (KD) (globoid cell leukodystrophy) is a degenerative, lysosomal storage disease, caused by a severe loss of galactocerebrosidase (GALC) enzymatic activity. The inheritance is autosomal recessive. KD affects the white matter of the central and peripheral nervous systems. We present a 3 year old boy in whom the disease had an 'infantile' or 'classic' presentation, with spasticity, irritability, and developmental delay. In addition the boy showed progressive severe motor and mental deterioration, difficulties in swallowing and decerebration. Molecular analysis revealed that the child is a compound heterozygote: p.Asp187Val (c.560A>T) and p.Ile250Thr (c.749T>C). The father was the carrier of p.Asp187Val (c.560A>T), while the mother was the carrier of the p.Ile250Thr (c.749T>C) in exon 6 of the GALC gene. The clinical course in this compound heterozygote is severe and the patient passed away at the age of 3 years. Genotype-phenotype relations are discussed in this Macedonian patient with KD. [ABSTRACT FROM AUTHOR]

Wildervanck syndrome (WS) combines features of Klippel-Feil syndrome (KFS), sixth nerve palsy, and deafness. This is a case of a 23 year old woman, diagnosed with KFS (a triad of short neck, low posterior hairline and restricted neck movements) at the age of 20 days. The manifestations of the WS in this patient are severe: she has torticollis, and an extremely severe scoliosis. In addition, she is short (-3 SD; parental target height + 0.8SD) and has mixed sensorineural and conductive deafness. She also has ptosis, strabismus and a high myopia. Radiologically, there are multiple coalitions of cervical vertebrae. Intelligence is unaffected (IQ 95), but deafness, strabismus and high myopia forced her early out of school. Karyotype is 46, XX. In brief, this is a patient with severe WS and additional anomalies. Short and/or reduced parental target height is a part of WS. [ABSTRACT FROM AUTHOR]

In Europe Rare Disease (RD) is the one which affects less than 1/2000, in the USA 1/1250, while in Japan RD is the one that affects fewer than 1/50,000 patients. EU estimates that 5-8000 distinct rare diseases affect 6-8% of the Population. The impact of rare diseases in the health systems is impresssive: at least 3 million patients in the UK, 4 million in Germany, and between 27 and 36 million EU citizens. There is not a precise register for rare diseases in the Republic of Macedonia. Rare diseases are becoming increasingly important as possible targets of new forms of treatment, as a valuable source of a novel insight in fundamental lows of biology, and in the specific mechanisms of many diseases. Molecular methods have created a better diagnosis and oftentimes treatment. Rare diseases pose significant problem for the patients, since their problems are often not recognized by the medical community and shunned by the health insurance. The cumulative costs of diagnosis and treatment of rare diseases is significant for any society and oftentimes not acceptable for developing countries. [ABSTRACT FROM AUTHOR]