Iodine Status in Cyprus and Neighboring Countries: A Review Article.

Despite the implementation of global iodine supplementation initiatives in the past decade, the problem of iodine deficiency persists as a significant public health concern in numerous countries. Although cretinism is now rare in developed countries, iodine deficiency can still lead to less severe cognitive deficits, which can negatively impact academic achievement, intellectual capacity, and work productivity. There is a scarcity of studies regarding the status of Cyprus, and the global database does not have any information pertaining to the prevalence of iodine deficiency in Cyprus. The geographical setting of the research is of importance as it pertains to the separation of Cyprus into two distinct areas. One region is predominantly inhabited by Greek Cypriots, where the practice of salt iodization is not mandatory. Conversely, the other region is primarily inhabited by Turkish Cypriots, who may potentially experience higher amounts of iodine contact due to their reliance on food imports from Turkey, where salt-iodisation is compulsory. The main objective of this study is to provide an overview of recent research conducted on the prevalence of iodine deficiency in Cyprus and neighboring Mediterranean nations. In this study, we assess the current method and subsequently offer public health recommendations for future research endeavors.

Molecular diagnosis in patients with monogenic diabetes mellitus, and detection of a novel candidate gene.

AIM: We aimed to investigate molecular genetic basis of monogenic diabetes (DM) and novel responsible candidate genes with targeted Next Generation Sequencing (NGS) and Whole Exome Sequencing (WES). METHODS: A hundred cases presenting with clinical findings and a family history of monogenic DM were included in the study. Molecular analysis was performed using an NGS panel including 14 genes. Following targeted NGS, WES was planned in cases in whom no variant was detected. RESULTS: Thirty different disease-causing variants in seven different genes were detected in thirty-five (35 %) cases with targeted NGS approach. Most common pathogenic variant was found in GCK gene in 25 (25 %) cases. Four different variants were detected in 4 (4 %) patients in ABCC8 gene. In 45 of 65 cases; WES analyses were done. A heterozygous c.2635C > T(p.Gln879Ter) variant was detected in IFIH1 gene in a patient with incidental hyperglycemia. In the segregation analysis affected mother was shown to be heterozygous for the same variant. CONCLUSION: Molecular etiology was determined in 35 % cases with the NGS targeted panel. Seventeen novel variants in monogenic DM genes have been identified. A candidate gene determined by WES analysis in a case that could not be diagnosed with NGS panel in this study.

A knowledge-based decision support system for inferring supportive treatment recommendations for diabetes mellitus.

BACKGROUND: Diabetes Mellitus (DM) is a significant risk, mostly causing blindness, kidney failure, heart attack, stroke, and lower limb amputation. A Clinical Decision Support System (CDSS) can assist healthcare practitioners in their daily effort and can improve the quality of healthcare provided to DM patients and save time. OBJECTIVE: In this study, a CDSS that can predict DM risk at an early stage has been developed for use by health professionals, general practitioners, hospital clinicians, health educators, and other primary care clinicians. The CDSS infers a set of personalized and suitable supportive treatment suggestions for patients. METHODS: Demographic data (e.g., age, gender, habits), body measurements (e.g., weight, height, waist circumference), comorbid conditions (e.g., autoimmune disease, heart failure), and laboratory data (e.g., IFG, IGT, OGTT, HbA1c) were collected from patients during clinical examinations and used to deduce a DM risk score and a set of personalized and suitable suggestions for the patients with the ontology reasoning ability of the tool. In this study, OWL ontology language, SWRL rule language, Java programming, Protégé ontology editor, SWRL API and OWL API tools, which are well known Semantic Web and ontology engineering tools, are used to develop the ontology reasoning module that provides to deduce a set of appropriate suggestions for a patient evaluated. RESULTS: After our first-round of tests, the consistency of the tool was obtained as 96.5%. At the end of our second-round of tests, the performance was obtained as 100.0% after some necessary rule changes and ontology revisions were done. While the developed semantic medical rules can predict only Type 1 and Type 2 DM in adults, the rules do not yet make DM risk assessments and deduce suggestions for pediatric patients. CONCLUSION: The results obtained are promising in demonstrating the applicability, effectiveness, and efficiency of the tool. It can ensure that necessary precautions are taken in advance by raising awareness of society against the DM risk.

Long-Term Endocrinologic Follow-Up of Children with Brain Tumors and Comparison of Growth Hormone Therapy Outcomes: A SingleCenter Experience.

OBJECTIVE: Brain tumors in childhood carry a high risk for endocrine disorders due to the direct effects of the tumor and/or surgery and radiotherapy. Somatotropes are vulnerable to pressure and radiotherapy; therefore, growth hormone deficiency is one of the most frequent abnormalities. This study aimed to evaluate endocrine disorders and recombinant growth hormone treatment outcomes in brain tumor survivors. MATERIALS AND METHODS: In this study, 65 (27 female) patients were classified into 3 groups as craniopharyngioma (n = 29), medulloblastoma (n = 17), and others (n = 19). "Others" group included astrocytoma, ependymoma, germinoma, pineoblastoma, and meningioma patients. Anthropometric data and endocrine parameters of patients and their growth outcome with/without recombinant growth hormone therapy were collected from medical records, retrospectively. RESULTS: Mean age at the first endocrinological evaluation was 8.7 ± 3.6 years (range: 1.0- 17.1 years). Height, weight, and body mass index standard deviation score, mean ± standard deviation (median) values were -1.7 ± 1.7 (-1.5), -0.8 ± 1.9 (-0.8), and 0.2 ± 1.5 (0.4), respectively. Hypothyroidism (central 86.9%, primary 13.1%) was detected during follow-up in 81.5% of patients. Primary hypothyroidism in medulloblastoma (29.4%) was significantly higher compared to other groups (P = .002). The frequency of hypogonadotropic hypogonadism, central adrenal insufficiency, and diabetes insipidus was significantly high in the craniopharyngioma cases. CONCLUSION: In our study, endocrine disorders other than growth hormone deficiency were also frequently observed. In craniopharyngioma cases, the response to recombinant growth hormone therapy was satisfactory. However, there was no improvement in height prognosis during recombinant growth hormone therapy in medulloblastoma patients. A multidisciplinary approach to the care of these patients, referral for endocrine complications, and guidelines on when recombinant growth hormone therapy is required.

Characterization of a Novel Frameshift Mutation Within the TRPS1 Gene Causing Trichorhinophalangeal Syndrome Type 1 in a Kindred Cypriot Family.

Trichorhinophalangeal syndrome (TRPS) is an extremely rare autosomal dominant multisystem disorder characterized by craniofacial and skeletal abnormalities. Three subtypes of TRPS have been described: TRPS type I, TRPS type II, and TRPS type III. Mutations in the TRPS1 gene can cause both TRPS type I and TRPS type III. Therefore, the genotype-phenotype correlation is crucial to determine the subtype. The current family study from Cyprus involves affected patients from 4 generations who presented with alopecia, unoperated umbilical hernia, caput quadratum, long philtrum, depressed nasal bridge, frontal bossing, pes planus, beaked nose, and some deformities in hands and feet. Sequence analysis of the TRPS1 gene revealed a novel c.2854_2858del (p.Asn952ArgfsTer2) frameshift variant leading to a premature stop codon. To the best of our knowledge, we report here the first case of a Turkish Cypriot family of 4 generations with a novel frameshift mutation leading to truncated protein in the TRPS1 gene causing TRPS type I clinical phenotype. Overall, as the genotype and phenotype correlation in TRPSI is still uncertain and complex, the present outcome can enhance our knowledge of this complicated, rare, and severe genetic disorder.

Mutations in AR or SRD5A2 Genes: Clinical Findings, Endocrine Pitfalls, and Genetic Features of Children with 46,XY DSD

Objective: Androgen insensivity syndrome (AIS) and 5α-reductase deficiency (5α-RD) present with indistinguishable phenotypes among the 46,XY disorders of sexual development (DSD) that usually necessitate molecular analyses for the definitive diagnosis in the prepubertal period. The aim was to evaluate the clinical, hormonal and genetic findings of 46,XY DSD patients who were diagnosed as AIS or 5α-RD. Methods: Patients diagnosed as AIS or 5α-RD according to clinical and hormonal evaluations were investigated. Sequence variants of steroid 5-α-reductase type 2 were analyzed in cases with testosterone/dihydrotestosterone (T/DHT) ratio of ≥20, whereas the androgen receptor (AR) gene was screened when the ratio was <20. Stepwise analysis of other associated genes were screened in cases with no causative variant found in initial analysis. For statistical comparisons, the group was divided into three main groups and subgroups according to their genetic diagnosis and T/DHT ratios. Results: A total of 128 DSD patients from 125 non-related families were enrolled. Birth weight SDS and gestational weeks were significantly higher in 5α-RD group than in AIS and undiagnosed groups. Completely female phenotype was higher in all subgroups of both AIS and 5α-RD patients than in the undiagnosed subgroups. In those patients with stimulated T/DHT <20 in the prepubertal period, stimulated T/DHT ratio was significantly lower in AIS than in the undiagnosed group, and higher in 5α-RD. Phenotype associated variants were detected in 24% (n=18 AIS, n=14 5α-RD) of the patients, revealing four novel AR variants (c.94G>T, p.Glu32*, c.330G>C, p.Leu110=; c.2084C>T, p.Pro695Leu, c.2585_2592delAGCTCCTG, p.(Lys862Argfs*16), of these c.330G>C with silent status remained undefined in terms of its causative effects. Conclusion: T/DHT ratio is an important hormonal criterion, but in some cases, T/DHT ratio may lead to diagnostic confusion. Molecular diagnosis is important for the robust diagnosis of 46,XY DSD patients. Four novel AR variants were identified in our study.

Identification of a Novel De Novo COMP Gene Variant as a Likely Cause of Pseudoachondroplasia.

Next-generation sequencing technology and advanced sequence analysis techniques are markedly speeding up the identification of gene variants causing rare genetic diseases. Pseudoachondroplasia (PSACH, MIM 177170) is a rare disease inherited in an autosomal dominant manner. It is known that variations in the cartilage oligomeric matrix protein (COMP) gene are associated with the disease. Here, we report a 39-month-old boy with short stature. He gave visible growth and development delayed phenotype after 12 months. Further genetic resequencing analysis was carried out to identified the disease-causing variant. Furthermore, computational approaches were used to characterize the effect of the variant. In this study, we identify and report a novel variation in the COMP gene, c.1420_1422del (p.Asn47del), causing a spontaneous form of PSACH in our patient. Our in silico model indicated that any mutational changes in this region are very susceptible to PASCH phenotype. Overall, this study is the first PSACH case in the Turkish Cypriot population. Moreover, this finding contributes to the concept that the genotype-phenotype correlation in COMP is still unknown and also improves our understanding of this complex disorder.

Evaluation of the Efficacy and Safety of 3 Different Management Protocols in Pediatric Diabetic Ketoacidosis.

OBJECTIVE: Management protocols for pediatric diabetic ketoacidosis (DKA) vary considerably among medical centers. The aim of this study was to investigate the efficacy and safety of 3 different fluid protocols in the management of DKA. METHODS: Fluid management protocols with sodium contents of 75, 100, and 154 mEq/L NaCl were compared. In all groups, after the initial rehydration, the protocols differed from each other in terms of the maintenance fluid, which had different rates of infusion and sodium contents. Clinical status and blood glucose levels were checked every hour during the first 12 hours. Biochemical tests were repeated at 2, 6, 12, 24, and 36 hours. RESULTS: The medical records of 144 patients were evaluated. Cerebral edema developed in 18% of the patients. The incidence of cerebral edema was lowest in the group that received fluid therapy with a sodium content of 154 mEq/L NaCl at least 4 to 6 hours and had a constant rate of infusion for 48 hours. The patients with cerebral edema had lower initial pH and HCO3 and severe dehydration with higher initial plasma osmolality. There was no significant difference between the groups in terms of the recovery times of blood glucose, pH, HCO3, and the time of transition to subcutaneous insulin therapy. CONCLUSIONS: Severity of acidosis and dehydration are associated with the development of cerebral edema. It can be concluded that fluid therapy with higher Na content and a constant maintenance rate may present less risk for the patient with DKA.

Unusual Glycemic Presentations in a Child with a Novel Heterozygous Intragenic INSR Deletion.

BACKGROUND: Mutations of the insulin receptor (INSR) gene lead to a wide spectrum of inherited insulin resistance (IR) syndromes. Among these, type A-IR, usually caused by dominant negative INSR mutations, generally presents peri-pubertally in girls. CASE: A 2.8-year-old girl was referred due to recurrent postprandial and fasting hypoglycemia. She had been born at full-term with birth weight 1.89 kg, and had developed transient neonatal diabetes. Examination showed satisfactory growth, reduced adipose tissue, acanthosis nigricans, and isolated thelarche. After 12 h of fasting, she developed hypoglycemia (glucose 2.8 mmol/L), with inappropriately raised plasma insulin concentration of 5.4 mU/L and suppressed fatty acids and ketone bodies. Oral glucose tolerance testing showed severely increased plasma insulin concentration (>300 mU/L) with hypoglycemia (glucose 1.6 mmol/L) at 2.5 h. She was initially managed on dietary modifications, cornstarch, and then trialed on acarbose for postprandial hyperinsulinemic hypoglycemia (PPHH) with some response. However, she was noted to have increased frequency of hyperglycemia after a couple of years of treatment. She was then switched to metformin and continued to have dietary carbohydrate modification including cornstarch that improved fasting tolerance, hyperglycemia, and postprandial hypoglycemia. Genetic testing identified heterozygous deletion of the last exon of the INSR gene, exon 22. CONCLUSION: We present a case of type A-IR, caused by a novel INSR deletion, presenting unusually early with transient neonatal diabetes, followed by episodes of hypoglycemia and hyperglycemia during later childhood. Early life presentations, including neonatal diabetes and PPHH, should lead to consideration of type A-IR.

The Incidence and Demographic Distribution of Type 1 Diabetes Mellitus in Children Aged 16 or Younger Between 2000 and 2016 in Cyprus

Objective: Type 1 diabetes (T1D) is a disease characterized by severe insulin deficiency. In 2008 our group studied the prevalence of diabetes in adults between 20-80 years of age in Cyprus but data regarding this incidence in the pediatric population is lacking. The objective of this study was to report the incidence of T1D among permanent inhabitants aged 16 years or younger between 2001-2016 in Cyprus. Methods: This study was a retrospective analysis. The patients were mainly evaluated and recorded at Dr. Burhan Nalbantoglu Hospital, Nicosia. Data was also reviewed from Famagusta Government Hospital, Kyrenia Government Hospital, Near East University Hospital and the Cyprus Turkish Diabetes Association. Results: A total of 107 subjects were diagnosed as T1D between 2001 and 2016 in the pediatric age group. Forty-nine (45.7%) were girls and 58 (54.3%) were boys. Of these 38.7% were resident in Nicosia, 30.2% Famagusta, 12.3% Kyrenia, 9.4% Guzelyurt and 7.5% Iskele. The proportion of newly diagnosed T1D was highest among children aged 9-12 years (35.5%) followed by children aged 5-8 years (32.7%). Newly diagnosed T1D most frequently presented in March and April. The overall mean incidence rate was 11.1/100,000 between 2001 and 2016. The incidence rates were similar and comparable among the years. Conclusion: This study is the first to analyze the incidence of T1D in Cyprus. Compared to other countries the incidence rate is intermediate. Our findings are similar to the incidence rates of T1D in South Cyprus and Turkey.

Evidence in obese children: contribution of tri-ponderal mass index or body mass index to dyslipidemia, obesity-inflammation, and insulin sensitivity.

Background Chronic inflammation plays a critical role in the development of obesity-related metabolic dysfunction. The tri-ponderal mass index (TMI) may be more effective than body mass index (BMI) for estimating body fat levels. This study compared the efficacy of BMI and TMI in screening for dyslipidemia, insulin sensitivity, and inflammation in childhood obesity. Methods This study included 80 children who were classified as normal weight, overweight or obese using standardized BMI (BMI standard deviation score [SDS]) and TMI measurements. Fasting blood glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), triglycerides, total cholesterol, liver function enzymes, leptin, serum free fatty acid (FFA), fetuin-A, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-6 levels were evaluated using both classification systems. Results LDL-C levels significantly differed within the groups by BMI, and serum FFA levels differed only according to the TMI. Serum MCP-1, TNF-α, IL-6, and fetuin-A levels showed no difference according to the TMI or BMI SDS. Fetuin-A levels did not differ between the insulin-resistant and non-resistant cases. Fetuin-A was the only inflammatory marker positively correlated with BMI. No inflammatory markers correlated with TMI. Fetuin-A, MCP-1, TNF-α, and IL-6 correlated with each other, but not with metabolic parameters. Conclusions BMI SDS and TMI were associated with metabolic disturbances in childhood obesity. Weight versus heightn values may be related more to metabolic parameters than to inflammatory changes.

Headliner in Physiology and Management of Childhood Asthma: Hypothalamic-Pituitary-Adrenal Axis.

Asthma is the most common chronic inflammatory disease of children. Inhaled corticosteroids (ICS) are the cornerstone of asthma therapy which are the most effective, commonly used treatment of persistent asthma. Mostly, studies on the relationship between asthma and cortisol have focused on side effects of treatment. Recently, asthmatic patients not treated with ICS have been reported to have an attenuated activity and/or responsiveness of their Hypothalamic-Pituitary- Adrenal (HPA) axis. Moreover, it has been proposed that asthma worsening with stress may be due to a dysfunctional HPA axis, or cortisol insensitivity due to chronic psychological stress through impaired glucocorticoid receptor expression or function. Although long-term ICS treatment might produce adrenal suppression or iatrogenic Cushing syndrome, improvement of adrenal function has also been detected in some of asthmatic cases. Thus, the response scheme of HPA axis still contains undiscovered features in asthma. The management of asthma can be improved by increasing knowledge on the role of HPA axis in asthma pathophysiology. The risk for side effects of ICS can be minimized through increased awareness, early recognition of at-risk patients and regular patient follow-up. This review was written to draw attention to the role of HPA axis in both asthma and its treatment and to illustrate a follow up algorithm of HPA axis in the management of asthma.

Joubert syndrome with multiple pituitary hormone deficiency.

Joubert syndrome (JS) and JS-related disorders are a group of developmental delay, multiple congenital anomalies and complex midbrain-hindbrain malformations. A few cases of JS with multiple pituitary hormone deficiency (MPHD) have been reported in literature. Here, we presented an unusual presentation of JS in a newborn with MPHD. This case is intended to draw attention to the rare association of JS and MDPH by increasing the awareness of this syndrome.

Accuracy of Tri-ponderal Mass Index and Body Mass Index in Estimating Insulin Resistance, Hyperlipidemia, Impaired Liver Enzymes or Thyroid Hormone Function and Vitamin D Levels in Children and Adolescents

Objective: Tri-ponderal mass index (TMI) has been reported to estimate body fat more accurately than body mass index (BMI). This study aimed to compare the efficacy of TMI and BMI in predicting insulin resistance (IR), hyperlipidemia, impaired liver enzymes or thyroid hormone function and vitamin D concentration. Methods: One hundred and forty-three overweight or obese children, based on BMI-standard deviation (SD) scoring (BMI-SDS) were studied retrospectively. TMI thresholds for overweight status were 16.0 kg/m3 for boys and 16.8 kg/m3 for girls and 18.8 kg/m3 for boys and 19.7 kg/m3 for girls for obese status. Results: Twenty-two overweight and eight obese children by BMI-SDS were classified as normal by TMI. Of the overweight children 22 (22.7%) had IR and IR was detected in 2 of 8 obese children with normal TMI. There was no increase in liver enzymes in any of the children with normal TMI. Forty-four obese children were overweight according to TMI and IR was detected in 40.9%. Thyroid stimulating hormone levels were significantly higher in BMI-based obese children. Vitamin D levels were similar in all groups of both classifications. Conclusion: When TMI was used there may be a risk of overlooking IR. However, if it is assumed that liver enzymes are elevated as a result of visceral adiposity, TMI can be used as an auxiliary parameter to show visceral effects of adiposity. Normal TMI may indicate that visceral organ functions have not deteriorated yet. More studies are needed to evaluate TMI as a clinical tool.

Incidence of Type 1 Diabetes in Children Aged Below 18 Years during 2013-2015 in Northwest Turkey

Objective: To assess the incidence of type 1 diabetes mellitus (T1DM) in children under 18 years of age in the northwest region of Turkey during 2013-2015. Methods: All newly diagnosed T1DM cases were recorded prospectively during 2013-2015. Total, as well as gender and age group specific (0-4, 5-9, 10-14 and 15-17 age) mean incidences per 100,000 per year were calculated. Results: There were 1,773 patients diagnosed during 2013-2015 (588 cases in 2013, 592 cases in 2014, 593 cases in 2015). Of these, 862 (48.6%) were girls and 911 (51.4%) were boys. The mean age at diagnosis was 9.2±4.2 years and it was not significantly different between girls (9.0±4.1 years) and boys (9.4±4.4 years) (p=0.052). The crude mean incidence was 8.99/100.000 confidence interval (CI) (95% CI: 8.58-9.42). Although mean incidence was similar between boys [8.98/100.000 (CI: 8.40 to 9.58)] and girls [9.01/100.000 (CI: 8.42 to 9.63)], there was male predominance in all groups except for 5-9 year age group. The standardized mean incidence was 9.02/100.000 according to the World Health Organization standard population. The mean incidence for the 0-4, 5-9, 10-14 and 15-17 age groups was 6.13, 11.68, 11.7 and 5.04/100.000 respectively. The incidence of T1DM was similar over the course of three years (p=0.95). A significant increase in the proportion of cases diagnosed was observed in the autumn-winter seasons. Conclusion: The northwest region of Turkey experienced an intermediate incidence of T1DM over the period of the study.

Klinefelter Syndrome in Childhood: Variability in Clinical and Molecular Findings

OBJECTIVE: Klinefelter syndrome (KS) is the most common (1/500­1/1000) chromosomal disorder in males, but only 10% of cases are identified in childhood. This study aimed to review the data of children with KS to assess the age and presenting symptoms for diagnosis, clinical and laboratory findings, together with the presence of comorbidities. METHODS: Twenty-three KS patients were analyzed retrospectively. Age at admission, presenting symptoms, comorbid problems, height, weight, pubertal status, biochemical findings, hormone profiles, bone mineral density and karyotype were evaluated. Molecular analysis was also conducted in patients with ambiguous genitalia. RESULTS: The median age of patients at presentation was 3.0 (0.04-16.3) years. Most of the cases were diagnosed prenatally (n=15, 65.2%). Other reasons for admission were scrotal hypospadias (n=3, 14.3%), undescended testis (n=2, 9.5%), short stature (n=1, 4.8%), isolated micropenis (n=1, 4.8%) and a speech disorder (n=1, 4.8%). The most frequent clinical findings were neurocognitive disorders, speech impairment, social and behavioral problems and undescended testes. All except two patients were prepubertal at admission. Most of the patients (n=20, 86.9%) showed the classic 47,XXY karyotype. Steroid 5 alpha-reductase 2 gene and androgen receptor gene mutations were detected in two of the three cases with genital ambiguity. CONCLUSION: Given the large number of underdiagnosed KS patients before adolescence, pediatricians need to be aware of the phenotypic variability of KS in childhood. Genetic analysis in KS patients may reveal mutations associated with other forms of disorders of sex development besides KS.

A Novel TBX19 Gene Mutation in a Case of Congenital Isolated Adrenocorticotropic Hormone Deficiency Presenting with Recurrent Respiratory Tract Infections.

INTRODUCTION: Congenital isolated adrenocorticotropic hormone deficiency (CIAD) is a rare disease characterized by low adrenocorticotropic hormone (ACTH) and cortisol levels. To date, recurrent pulmonary infections in infancy have not been reported as an accompanying symptom of CIAD. CASE PRESENTATION: A 7-year-old boy was hospitalized nine times for recurrent lower respiratory tract infections. The results of all tests for the possible causes of wheezing were within the normal limits. His ACTH and cortisol levels were persistently low. All other pituitary hormone levels, and adrenal ultrasound and pituitary magnetic resonance imaging results, were normal. Molecular analyses confirmed the diagnosis of CIAD by identifying compound heterozygosity for two mutations in the TBX19 gene. The first was a novel frameshift c.665delG variant in exon 4 of the TBX19 gene, leading to premature termination that was predicted to result in a non-functional truncated protein. The second was a nonsense C-to-T transition in exon 6 of the TBX19 gene, resulting in an arg286-to-ter mutation (dbSNP: rs74315376). Both parents were heterozygous for one of the mutations. CONCLUSION: Here, we presented a new mutation in the TBX19 gene in a patient with CIAD who presented with recurrent respiratory tract infections. This expands the mutation spectrum in this disorder. To conclude, adrenal insufficiency should be considered in patients with unexplained recurrent infections to prevent a delay in diagnosis.

A rare cause of upper airway obstruction: isolated demyelinating brainstem lesion.

Acute upper airway obstruction derived from any cause can be a life-threatening emergency in pediatric patients. The major causes are infection, foreign body aspiration, and trauma. However, acute neurological disorders occasionally may manifest as severe airway obstruction.In our case, we report a 10-year-old patient presenting with prominent upper airway obstruction requiring intubation and respiratory support. He also had fever, encephalopathy, and involvement of multiple cranial nerves. Cranial magnetic resonance imaging showed a hyperintense lesion covering all of the medulla oblongata on T2-weighted images and a lesion that was hypointense on T1-weighted images with no enhancement. Diffusion maps were normal. High-dose steroids and then intravenous immunoglobulin were given because these findings were mostly consistent with an inflammatory demyelinating process in the brainstem. A dramatic improvement was observed, and he was extubated on the 10th day. He completely recovered within 3 weeks without any neurological deficit.We emphasize that emergency physicians should be familiar with the airway manifestations of acute neurological disorders. Although rare, acute demyelinating brainstem disorders should be considered a part of the differential diagnosis of upper airway obstruction in children. Prompt recognition of this entity in light of additional neurological findings, neuroimaging, and other laboratory test results is critical. Early immunomodulatory treatment of these patients can be lifesaving.