Natural history of ENPP1 deficiency: Nationwide Turkish Cohort Study of autosomal-recessive hypophosphataemic rickets type 2.

OBJECTIVE: Autosomal-recessive hypophosphataemic rickets type 2 (ARHR2) is a rare disease that is reported in survivors of generalized arterial calcification of infancy (GACI). DESIGN, PATIENTS AND MEASUREMENT: The objective of this study was to characterize a multicenter paediatric cohort with ARHR2 due to ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1) deficiency and with a diagnosis of GACI or GACI-related findings. The clinical, biochemical and genetic characteristics of the patients were retrospectively retrieved. RESULTS: We identified 18 patients from 13 families diagnosed with ARHR2. Fifteen of the patients had an ENPP1 variation confirmed with genetic analyses, and three were siblings of one of these patients, who had clinically diagnosed hypophosphataemic rickets (HRs) with the same presentation. From nine centres, 18 patients, of whom 12 (66.7%) were females, were included in the study. The mean age at diagnosis was 4.2 ± 2.2 (1.6-9) years. The most frequently reported clinical findings on admission were limb deformities (66.6%) and short stature (44.4%). At diagnosis, the mean height SD was -2.2 ± 1.3. Five of the patients were diagnosed with GACI in the neonatal period and treated with bisphosphonates. Other patients were initially diagnosed with ARHR2, but after the detection of a biallelic variant in the ENPP1 gene, it was understood that they previously had clinical findings associated with GACI. Three patients had hearing loss, and two had cervical fusion. After the treatment of HRs, one patient developed calcification, and one developed intimal proliferation. CONCLUSION: ARHR2 represents one manifestation of ENPP1 deficiency that usually manifests later in life than GACI. The history of calcifications or comorbidities that might be associated with GACI will facilitate the diagnosis in patients with ARHR2, and patients receiving calcitriol and phosphate medication should be carefully monitored for signs of calcification or intimal proliferation.

Schwartz-Jampel Syndrome Type-1: Compound Heterozygosity of Two Novel Variants.

Schwartz-Jampel Syndrome (SJS) type-1 (OMIM; #255800), a rare cause of skeletal dysplasia, is characterized by myotonic myopathy, chondrodystrophy, short stature, facial and eye abnormalities. SJS Type-1 develops due to variations in the HSPG2 gene which produces the "perlecan" molecule, one of the main proteoglycans of the basement membrane. A 6-year-old girl presented with short stature, a mask face, shrunken lips, narrow palpebral opening due to blepharospasm, stiffness of facial muscles, micrognathia, overlapping teeth, a short neck, and a bell-shaped thorax due to myotonic myopathy. She was diagnosed with SJS type-1 due to compound heterozygosity of two novel variations in the HSPG2 gene. In patients with short stature and an accompanying myotonic myopathy SJS should be considered. Compound heterozygosity may cause typical clinical findings of SJS. In case of suspicion creatinine kinase levels can be measured, and the determination of myotonia may require evaluation with electromyography. Once the diagnosis is made, patients should be carefully monitored in terms of growth, neuromuscular disorders, joints problems and bone health.

Effects of applications manual pressure and shotblocker to reduce needle-related pain and fear in children with type 1 diabetes mellitus.

BACKGROUND: Pain and fear associated with insulin injections can cause children with type 1 diabetes mellitus to avoid insulin injections and skip doses. OBJECTIVE: To evaluate and compare pain and fear levels in children aged 6-12 years receiving subcutaneous insulin injection using the manual pressure and ShotBlocker methods. METHODS: A randomized controlled study was conducted with 90 children with type 1 diabetes who were allocated using block randomization to the manual pressure, ShotBlocker, and control groups (n = 30 in each group). Fear and pain levels were rated by the children, their parents, and a member of the study team immediately before and after insulin injection using the Children's Fear Scale and Wong-Baker Faces Pain Rating Scale, respectively. RESULTS: All groups had similar self-, parent-, and researcher-reported levels of preprocedural pain and fear (p > 0.05). However, pain and fear scores were lower in the manual pressure and ShotBlocker groups than in the control group after injection (p = 0.0001). There was no significant difference in pain and fear scores between the two intervention groups (p > 0.05). CONCLUSION: Manual pressure and the ShotBlocker both reduced fear and pain associated with insulin injection in 6- to 12-year-old children with type 1 diabetes. IMPLICATIONS FOR PRACTICE: Both the manual pressure and ShotBlocker methods can easily be applied in children receiving insulin injections. As manual pressure is completely cost- and equipment-free, it is a useful option to reduce pain and fear related to insulin injection. CLINICAL TRIAL REGISTRATION NUMBER: National Institutes of Health (NIH), ClinicalTrials.gov, NCT05789810.

Diagnostic Pitfalls of a Newborn with Congenital Nephrogenic Diabetes Insipidus.

Congenital nephrogenic diabetes insipidus (NDI) is a rare cause of hypernatremia in newborns. Central diabetes insipidus (CDI) is the main differential diagnosis of NDI. NDI responds poorly to desmopressin acetate (DDAVP) treatment while this is the mainstay of CDI management. Therefore, an early and correct diagnosis of NDI is crucial to avoid the complications of inappropriate therapy. Here, we report a newborn with hypernatremia and hypotonic polyuria. The patient was initially responsive but subsequently unresponsive to intranasal DDAVP treatment in regard to urine output and serum sodium levels. A novel hemizygous missense mutation (c.632T>C, p.L211P) in the AVPR2 gene was found both in the baby and his mother, and the diagnosis of congenital NDI was established. After hydrochlorothiazide treatment and hypo-osmolar formula were given, urine volume was decreased, and serum sodium levels were normalized. Early recognition and appropriate management of NDI can prevent complications of hypernatremic dehydration in young infants.

Human chorionic gonadotrophin secreting adrenocortical neoplasm presenting with peripheral precocious puberty in an infant.

Adrenocortical tumor (ACT) is a rare malignant tumor which usually present with Cushing syndrome and virilization. Paraneoplastic syndromes (PNS) due to neoplasms can occur with peptides or cytokines secreted by the tumor. Here, we report a 13-month-old-male presented with severe masculinization. He had signs of precocious puberty with enlarged testicles, very high testosterone levels but low levels of gonadotrophins, and elevated ß-hCG. He underwent a left nephrectomy. The histopathological evaluation revealed a diagnosis of adrenocortical neoplasm. The levels of androgens and ß-hCG normalized after the resection of tumor, and the clinical findings improved within few months. We report the first pediatric patient with peripheral precocious puberty due to an ACT that secretes ß-hCG as PNS. A ß-hCG secreting ACT can cause severe virilization due to increased gonadal androgens stimulated by ß-hCG as well as due to increased adrenal androgens from the tumor.

The effects of the covid-19 pandemic on puberty: a cross-sectional, multicenter study from Turkey.

BACKGROUNDS: During the Coronavirus-19 disease (Covid-19) pandemic it was observed that the number of girls presenting with early puberty had increased. The aim of this study was to carry out a retrospective evaluation of the characteristics of girls who had been referred for evaluation of precocious puberty in five different pediatric endocrinology units, before and during the pandemic. METHODS: The study participants comprised 359 girls who were assigned into 2 groups a pre-pandemic group (n:214) and a pandemic group (n:145). Those participants (n:99) who had medical records in the follow-up period were classified into 3 subgroups according to the time of presentation and follow-up visits (group-1: first admission and follow-up visit before the pandemic, group-2: first admission before the pandemic, the follow-up visit during the pandemic, group-3: first admission and follow-up visit during the pandemic). RESULTS: The age at presentation and age at pubertal onset were both significantly lower in the pandemic group than those in the pre-pandemic group(8.1 vs 8.6, p: < 0.001,7.7 vs 7.9,p:0.013, respectively). There was no significant difference between the body mass index standard deviation scores (BMI-SDS) values of the groups (0.57 vs 0.51, p:0.430). The initiation rate of pubertal suppression therapy at the time of presentation was significantly higher in the pandemic group compared to that of the pre-pandemic group (7.7%vs 27.5%), and in groups-2 & 3 compared to group-1, during follow-up (20%&44%vs 8%). CONCLUSION: Our research showed that the onset of puberty occurred earlier in the pandemic period compared to the previous year, and the need for pubertal suppression therapy increased during the pandemic.

Psychometric Properties of the Turkish Version of the Diabetes Strengths and Resilience Measure for Adolescents with Type 1 Diabetes

Objective: Resilience in diabetes refers to the capacity overcome diabetes-related challenges to achieve favorable psychosocial and health outcomes. Despite the known benefits of resilience in adolescents with type 1 diabetes mellitus (T1DM), there tends to be more emphasis on risk factors in research and practice. This study evaluated the psychometric properties of the Diabetes Strengths and Resilience Measure for Adolescents with Type 1 Diabetes (DSTAR-Teen) in Turkey. Methods: This descriptive, methodological study was conducted between October 2020 and May 2021. The Turkish DSTAR-Teen was administered to 120 adolescents with T1DM, and the data were evaluated using Cronbach's alpha coefficients, factor analyses, test-retest correlation, and item-total score correlations. Results: The Turkish DSTAR-Teen has 12 items in two factors that explained 50.64% of the total variance. Confirmatory factor analysis revealed goodness-of-fit and comparative fit indices of 0.92 and 0.95, respectively. The total Cronbach's alpha value of the scale was 0.85. Item-total score correlations ranged from 0.49 to 0.74 (p<0.001). Conclusion: Our analyses showed that the Turkish DSTAR-Teen is a valid and reliable instrument in Turkish adolescents with T1DM. The Turkish DSTAR-Teen can be used to evaluate strengths and resilience associated with diabetes management in adolescents with T1DM in Turkey.

Familial early-onset obesity in Turkish children: variants and polymorphisms in the melanocortin-4 receptor (MC4R) gene.

OBJECTIVES: Genetic factors have a key role in childhood obesity with higher rates in children than adults. Among the monogenic types of non-syndromic obesity, melanocortin-4 receptor (MC4R) deficiency is the most frequent cause. Beside pathogenic variants, single-nucleotide polymorphisms in MC4R gene are also associated with lower energy expenditure. The aim of this study was to estimate the frequency of MC4R variants and polymorphisms in a cohort of Turkish children and adolescents with severe early-onset obesity, and to understand the clinical features of patients. METHODS: Patients, 1-17 years of age, with the onset of obesity before 10 years of age and a body mass index (BMI) standard deviation score (SDS) of >2.3, and who had a family history of early-onset obesity in at least one of their first-degree relatives were included in the study. Beside routine blood tests genetic analyses for MC4R gene were performed. RESULTS: Analyses of MC4R revealed previously known variations in three (3.5%) patients, and pathogenic polymorphisms related with obesity in four (4.7%) patients. BMI SDS values were between 2.8 and 5.5 SDS in the pathogenic variant carrier group, and 2.8-4.9 SDS in the polymorphism group. Mean BMI SDS in variant-negative group was 3.4 ± 0.82. CONCLUSIONS: Investigation of the MC4R in individuals with early-onset obesity and presence of obesity first-degree relatives is important. Hypertension is a rare comorbidity compared to other causes. Contrary to studies reporting that insulin resistance was absent or very rare, we found it as a frequent finding in both pathogenic variants and polymorphisms of MC4R.

Sacroiliac joint involvement in children with inflammatory bowel diseases.

Objective: Sacroiliitis (SI), an inflammatory arthropathy, may accompany pediatric inflammatory bowel diseases (IBDs), present with non- specific back pain, hence might be unnoticed. The aims of this study were to assess the frequency of the SI in children with IBD and determine the characteristics of the association of SI with the clinical hallmarks of the IBD. Methods: In this prospective, cross sectional study, twenty-seven children with IBD, 7-18 years of age were evaluated. Patients with low back pain or stiffness, alternating buttock pain, or hip pain were examined for the presence of SI. The radiologic manifestations on X-ray suggesting sacroilitis were confirmed with Magnetic resonance imaging (MRI). Results: Twenty-seven children (16 girls, female/male=1.45), with mean age of 12.55±3.6 years, of which 52% had ulcerative colitis (UC), 41% had Crohn's disease (CD), and two had indeterminate colitis (IC). The median time from IBD diagnosis was 6.0 (18.0) months for patients with SI and 12.0 (13.5) months for patients without SI. Low back pain or stiffness was observed in 13 patients (48%). SI was present in eight (30%) of the children with IBD. The patients with CD were more prone to SI (45% of CD vs. 21% of UC patients). All patients with SI were negative for HLA-B27 genotyping. The disease activity and gender were not associated with increased risk for SI. MRI was remarkable for bone marrow edema in all of the patient, followed by erosions in six of them (75%), synovial enhancement observed in five (63%), and erosion associated enthesitis of the pelvic region was observed in two (25%) of the patients. Conclusion: SI may remain obscured in children with IBD. Children with CD are more prone to SI than those with UC. Pediatric rheumatology-pediatric gastroenterology collaboration might augment screening in at-risk patients.

Steroid Hormone Profiles and Molecular Diagnostic Tools in Pediatric Patients With non-CAH Primary Adrenal Insufficiency.

CONTEXT: There is a significant challenge of attributing specific diagnoses to patients with primary adrenal insufficiency of unknown etiology other than congenital adrenal hyperplasia (non-CAH PAI). Specific diagnoses per se may guide personalized treatment or may illuminate pathophysiology. OBJECTIVE: This work aimed to investigate the efficacy of steroid hormone profiles and high-throughput sequencing methods in establishing the etiology in non-CAH PAI of unknown origin. METHODS: Pediatric patients with non-CAH PAI whose etiology could not be established by clinical and biochemical characteristics were enrolled. Genetic analysis was performed using targeted-gene panel sequencing (TPS) and whole-exome sequencing (WES). Plasma adrenal steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls. This study comprised 18 pediatric endocrinology clinics with 41 patients (17 girls, median age: 3 mo, range: 0-8 y) with non-CAH PAI of unknown etiology. RESULTS: A genetic diagnosis was obtained in 29 (70.7%) patients by TPS. Further molecular diagnosis could not be achieved by WES. Compared to a healthy control group, patients showed lower steroid concentrations, most statistically significantly in cortisone, cortisol, and corticosterone (P < .0001, area under the receiver operating characteristic curve: .96, .88, and .87, respectively). Plasma cortisol of less than 4 ng/mL, cortisone of less than 11 ng/mL, and corticosterone of less than 0.11 ng/mL had a greater than 95% specificity to ensure the diagnosis of non-CAH PAI of unknown etiology. CONCLUSION: Steroid hormone profiles are highly sensitive for the diagnosis of non-CAH PAI of unknown etiology, but they are unlikely to point to a specific molecular diagnosis. TPS is an optimal approach in the molecular diagnosis of these patients with high efficacy, whereas little additional benefit is expected from WES.

Evaluation of metabolic parameters and aortic elasticity in normotensive children with premature adrenarche.

OBJECTIVES: Premature adrenarche may be associated with an intrauterine programmed metabolic syndrome which should be considered as a warning sign for coronary heart disease due to accelerated atherosclerosis, hypertension, type 2 diabetes mellitus (DM), and polycystic ovary syndrome. METHODS: Seventy-three patients with premature adrenarche were evaluated for metabolic parameters and aortic elasticity to evaluate the susceptibility to atherosclerosis and compared with a control group. The patients were examined in two groups as overweight and nonoverweight, and metabolic and cardiac parameters were also compared among these groups. Strain, distensibility, and stiffness index parameters were used to evaluate aortic elasticity. RESULTS: Biochemical parameters and cardiac measurements were not statistically different between patients and controls. They also did not differ between patients with normal weight and overweight groups. Atherogenic index and insulin resistance were closely related and a positive correlation between cholesterol and triglyceride, and ascending aortic stiffness was found. CONCLUSIONS: The results may suggest that cholesterol and triglyceride-related arterial involvement is more involved in the pathogenesis of arterial stiffness. It can be considered that 'being overweight' or 'having metabolic profile characterized by insulin resistance and dyslipidemia' are the major coexisting factors influencing the vascular structure, rather than increased androgens and premature adrenarche itself.

Significant improvement in bone mineral density in pediatric celiac disease: even at six months with gluten-free diet.

OBJECTIVES: Patients with celiac disease had significantly decreased bone mineral density even in patients with no gastrointestinal symptoms. Only few bone studies are available on pediatric patients with celiac disease. METHODS: Forty-six patients underwent measurement of areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) before the initiation of gluten-free diet. Anthropometric, laboratory and DXA measurements at baseline and at sixth month of the treatment were compared. RESULTS: The frequency of low aBMD Z-score (≤-1 SDS) in both or any site was found to be 78.2% in this study. Of 16 patients with an aBMD Z-score of <-2 SDS five gained more than 1 SDS, and one gained more than 2 SDS. Nine of 20 patients with an aBMD Z-score of <-1 SDS completely normalized. CONCLUSIONS: The results of the study showed that low BMD is common in children with celiac disease at the time of diagnosis and could improve in a short period of six months with a strict gluten-free diet and adequate supplementation of calcium and vitamin D.

Ocular surface evaluation in pediatric Hashimoto's thyroiditis without thyroid-associated ophthalmopathy / Avaliação da superfície ocular na tireoidite de Hashimoto pediátrica sem oftalmopatia associada à tireoide

ABSTRACT Purpose: We aimed to assess ocular surface characteristics in children with Hashimoto's thyroiditis without thyroid-associated ophthalmopathy and compare the results with those of healthy children. Methods: Twenty-two children with Hashimoto's thyroiditis (Group 1) and 20 healthy children without any ocular and/or systemic disorder (Group 2) were enrolled in the study. Ocular Surface Disease Index questionnaire, tear film osmolarity measurement (TearLab Osmolarity System, San Diego, CA, USA), Schirmer and tear film breakup time tests, meibography, and conjunctival brush cytology were performed and compared the results between the groups. Results: The study group included 19 girls and 3 boys in Group 1 and 12 girls and 8 boys in Group 2 (p=0.081). Thyroid-associated ophthalmopathy was not identified in any of the patients. Mean tear film osmolarity was 310.23 ± 11.98 mOsm/l in Group 1 and 313.60 ± 15.03 mOsm/l in Group 2 (p=0.424). Mean Schirmer test score was lower in Group 1 (14.91 ± 6.27) compared with Group 2 (23.60 ± 5.63) (p=0.001). Mean tear film breakup time was lower in Group 1 (11.78 ± 4.07) compared with Group 2 (15.1 ± 1.6) (p=0.013). Moreover, mean meibomian gland area loss was 25.01% ± 10.04% in Group 1 and 16.54% ± 6.02% in Group 2 (p=0.002). Conjunctival cytologic analysis in Group 1 revealed grade 0 changes in 6 patients (27.3%), grade 1 changes in 14 patients (63.6%), and grade 2 changes in 2 patients (9.1%), whereas 18 patients (90%) had grade 0 changes and 2 patients (10%) had grade 1 changes (p=0.001) in Group 2. Conclusions: The study demonstrates several ocular surface changes in children with Hashimoto's thyroiditis. These findings may indicate a tendency for dry eye in pediatric Hashimoto's thyroiditis patients without clinical evidence of thyroid-associated ophthalmopathy.

RESUMO Objetivo: Avaliar as características da superfície ocular em crianças com tireoidite de Hashimoto sem oftalmopatia associada à tireoide e comparar os resultados com aqueles de crianças saudáveis. Métodos: Vinte e duas crianças com tireoidite de Hashimoto (Grupo 1) e 20 crianças saudáveis sem qualquer distúrbio ocular e/ou sistêmico (Grupo 2) participaram do estudo. Utilizou-se o questionário Índice da Doença da Superfície Ocular, medida de osmolaridade do filme lacrimal (Tearlab Osmolarity System, San Diego, CA, EUA), teste de Schirmer e tempo de ruptura do filme lacrimal, meibografia e citologia do raspado conjuntival e comparação dos resultados entre os grupos. Resultados: O grupo de estudo incluiu 19 meninas e 3 meninos no Grupo 1 e 12 meninas e 8 meninos no Grupo 2 (p=0,081). A oftalmopatia associada à tireoide não foi identificada em nenhum dos pacientes. A média da osmolari­dade do filme lacrimal foi 310,23 ± 11,98 mOsm/l no Grupo 1 e 313,60 ± 15,03 mOsm/l no Grupo 2 (p=0,424). A média do escore do teste de Schirmer foi menor no Grupo 1 (14,91 ± 6,27) do que no Grupo 2 (23,60 ± 5,63) (p=0,001). A média do tempo de ruptura do filme lacrimal foi menor no Grupo 1 (11,78 ± 4,07) em comparação com o Grupo 2 (15,1 ± 1,6) (p=0,013). Além disso, a média da perda de área da glândula meibomiana foi 25,01% ± 10,04% no Grupo 1 e 16,54% ± 6,02% no Grupo 2 (p=0,002). A análise da citologia conjuntival no Grupo 1 revelou alterações de grau 0 em 6 pacientes (27,3%), alterações de grau 1 em 14 pacientes (63,6%) e alterações de grau 2 em 2 pacientes (9,1%), enquanto 18 pacientes (90%) com alteração de grau 0 e 2 pacientes (10%) com alteração de grau 1 (p=0,001) no Grupo 2. Conclusões: O estudo demonstra várias alterações da superfície ocular em crianças com tireoidite de Hashimoto. Esses achados podem indicar uma tendência para olho seco em pacientes pediátricos com tireoidite de Hashimoto, sem evidências clínicas de oftalmopatia associada à tireoide.

The relationship between vitamin D level and hepatosteatosis in obese children.

OBJECTIVE: The increasing incidence of obesity in children is a significant risk factor for nonalcoholic fatty liver disease and obesity-associated morbidity. In the present study, we aimed to explore the correlation between Vitamin D level and hepatosteatosis in obese children. METHODS: A total of 110 children aged 10-16 years who presented to pediatric endocrinology outpatient clinic for obesity were enrolled. The study was completed in a single season between September and November. Hepatosteatosis was diagnosed by ultrasonography. The patients were grouped into two groups: Group 1 comprised patients with hepatosteatosis and Group 2 consisted of patients without hepatosteatosis. 25 hydroxy (25-OH) Vitamin D levels were compared between patients with and without hepatosteatosis. RESULTS: No statistically significant difference was observed between 25-OH Vitamin D levels of patients with and without hepatosteatosis. When the effects of age and sex were kept constant, there was no significant correlation between Vitamin D level and aspartate aminotransferase, alanine aminotransferase, and body mass index values. CONCLUSION: Unlike the results of the previous studies, we were unable to detect any significant difference between Vitamin D levels of obese patients with and without hepatosteatosis. We think that obesity, rather than Vitamin D status, that is, in fact, independently associated with nonalcoholic fatty liver disease. Larger studies are needed to investigate the impact of Vitamin D in children with obesity with hepatosteatosis.

Obesity-related thyroiditis in childhood: relationship with insulin resistance.

Background Thyroid dysfunction is the most common hormonal abnormality in obesity. It should actually be considered as an adaptation response to fat excess. However, little has been reported on the morphology of the thyroid gland, and no data regarding the relationship between thyroid gland changes and metabolic parameters are available in obese adolescents. Objective The study aimed to evaluate the frequency of non-autoimmune thyroiditis in obese adolescents and compare the metabolic status of patients with or without thyroiditis. Methods A total of 218 obese children and 49 age-matched control healthy children were included. Thyroid ultrasonography (USG) was performed in all participants, as well as thyroid hormone levels, thyroid antibodies (Abs), lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (HsCRP) were determined. Obese children were divided into three groups according to the presence of thyroid autoantibodies and USG findings of thyroiditis (Group-1: Abs [-], normal thyroid morphology/Group-2: Abs [+], abnormal thyroid morphology/Group-3: Abs [-], abnormal thyroid morphology). The relationship between body mass index, metabolic parameters and thyroid gland status was analyzed. Results Seventy-two of 218 obese patients (33%) had non-autoimmune thyroiditis (Group-3). The rate of insulin resistance was significantly higher in Group-3 than in Group-1 (p = 0.024). Similarly, the frequency of metabolic syndrome (MS) was higher in Group-3 (44.3%) than in Group-1 (27.1%) (p = 0.014). Conclusions Obese adolescents with non-autoimmune thyroiditis had a higher incidence of insulin resistance. This finding supported the hypothesis that insulin resistance may have an effect on thyroid morphology. Further randomized trials investigating this relationship are required.

Ocular surface evaluation in pediatric Hashimoto's thyroiditis without thyroid-associated ophthalmopathy.

PURPOSE: We aimed to assess ocular surface characteristics in children with Hashimoto's thyroiditis without thyroid-associated ophthalmopathy and compare the results with those of healthy children. METHODS: Twenty-two children with Hashimoto's thyroiditis (Group 1) and 20 healthy children without any ocular and/or systemic disorder (Group 2) were enrolled in the study. Ocular Surface Disease Index questionnaire, tear film osmolarity measurement (TearLab Osmolarity System, San Diego, CA, USA), Schirmer and tear film breakup time tests, meibography, and conjunctival brush cytology were performed and compared the results between the groups. RESULTS: The study group included 19 girls and 3 boys in Group 1 and 12 girls and 8 boys in Group 2 (p=0.081). Thyroid-associated ophthalmopathy was not identified in any of the patients. Mean tear film osmolarity was 310.23 ± 11.98 mOsm/l in Group 1 and 313.60 ± 15.03 mOsm/l in Group 2 (p=0.424). Mean Schirmer test score was lower in Group 1 (14.91 ± 6.27) compared with Group 2 (23.60 ± 5.63) (p=0.001). Mean tear film breakup time was lower in Group 1 (11.78 ± 4.07) compared with Group 2 (15.1 ± 1.6) (p=0.013). Moreover, mean meibomian gland area loss was 25.01% ± 10.04% in Group 1 and 16.54% ± 6.02% in Group 2 (p=0.002). Conjunctival cytologic analysis in Group 1 revealed grade 0 changes in 6 patients (27.3%), grade 1 changes in 14 patients (63.6%), and grade 2 changes in 2 patients (9.1%), whereas 18 patients (90%) had grade 0 changes and 2 patients (10%) had grade 1 changes (p=0.001) in Group 2. CONCLUSIONS: The study demonstrates several ocular surface changes in children with Hashimoto's thyroiditis. These findings may indicate a tendency for dry eye in pediatric Hashimoto's thyroiditis patients without clinical evidence of thyroid-associated ophthalmopathy.

Hepatopathies in children and adolescents with type 1 diabetes.

Background Diabetes and hepatosteatosis are dramatically increasing in childhood. Non-alcoholic fatty liver disease (NAFLD) is defined as a common disorder in adulthood, especially with type-2 diabetes and metabolic syndrome, while very few studies are available on liver health in children with type-1 diabetes. Patients and methods One hundred and ten (52 males and 58 females) patients with type-1 diabetes aged between 8 and 18 years were examined. The lipid profile, liver enzymes and hepatobiliary ultrasound findings of patients were investigated in terms of hepatopathies. Patients diagnosed with fatty liver were evaluated by pediatric gastroenterology specialists for the differential diagnosis and exclusion of other etiologies. The relationships between hepatopathy and age, pubertal status, the duration of diabetes and glycemic control were evaluated. Results Hepatopathy was found in 17 (15.5%) patients. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were normal and did not correlate with the ultrasonography (USG) findings. Hyperechogenicity detected by USG, whether it is true fat or glycogen hepatopathy, was found to be associated with "poor glycemic control" independently of age, puberty status and the duration of diabetes. Conclusions This study contributes to the literature in terms of the relationship between liver health and glycemic control in pediatric type-1 diabetes. Hepatopathies were releated with poor glycemic control independently of the duration of diabetes. This suggested that liver disorders should be considered as one of the subacute complications of diabetes. It was concluded that routine screening for comorbidities and complications in type-1 diabetes should also include hepatobiliary USG, as liver enzymes alone are inadequate for detecting hepatopathies.

Magnesium and Anti-phosphate Treatment with Bisphosphonates for Generalised Arterial Calcification of Infancy: A Case Report

Generalized arterial calcification of infancy (GACI) is a rare autosomal-recessive disorder, characterized by calcification of the internal elastic lamina, fibrotic myointimal proliferation of muscular arteries and resultant arterial stenosis. Treatment with bisphosphonates has been proposed as a means of reducing arterial calcifications in GACI patients, although there is no formalized treatment approach. The case reported here was a patient with severe GACI diagnosed at three months of age who had no response to bisphosphonate treatment, but clinically improved after the initiation of magnesium and anti-phosphate (using calcium carbonate) treatments. In patients unresponsive to bisphosphonate, magnesium and anti-phosphate treatment may be attempted.

Genetic and Clinical Characteristics of Patients with Vitamin D Dependent Rickets Type 1A

Objective: Vitamin D dependent rickets type 1A (VDDR1A) is an autosomal recessive disorder caused by mutations in the 1α-hydroxylase gene (CYB27B1). As it may be confused with nutritional rickets and hypophosphatemic rickets, genetic analysis is important for making a correct diagnosis. Methods: We analysed genomic DNA from 11 patients from eight different Turkish families. The patients were recruited for our studies if they presented with a diagnosis of VDDR. Results: The mean ± standard deviation age at diagnosis was 13.1±7.4 months. Seven patients had mild hypocalcemia at presentation while four patients had normal calcium concentrations. All patients underwent CYP27B1 gene analysis. The most prevalent mutation was the c.195 + 2T>G splice donor site mutation, affecting five out of 11 patients with VDDR1A. Two patients from the fourth family were compound heterozygous for c.195 + 2T>G and c.195 + 2 T>A in intron-1. Two patients, from different families, were homozygous for a previously reported duplication mutation in exon 8 (1319_1325dupCCCACCC, Phe443Profs*24). One patient had a homozygous splice site mutation in intron 7 (c.1215 + 2 T>A) and one patient had a homozygous mutation in exon 9 (c.1474 C>T). Conclusion: Intron-1 mutation was the most common mutation, as previously reported. All patients carrying that mutation were from same city of origin suggesting a "founder" or a "common ancestor" effect. VDDR1A should definitely be considered when a patient with signs of rickets has a normal 25-OHD level or when there is unresponsiveness to vitamin D treatment.

A case series of benign transient hyperphosphatasemia from a pediatric endocrinology reference health facility in Turkey.

INTRODUCTION: Benign transient hyperphosphatasemia (BTH), even a known condition, is not very well managed by primary care physicians. The diagnostic criteria for BTH were alkaline phosphatase (ALP) levels above 3-5 times greater than the age adjusted upper limit of normal among children under 5 years with no evidence of liver or bone disease whose ALP values resolved within 4 months. METHODS: This study involved 15 patients aged 0-5 years, who were referred to the pediatric endocrinology clinic for elevated ALP levels. They were diagnosed with BTH. We examined demographic and biochemical parameters including ALP and ALP isoenzymes, liver enzymes, calcium, phosphate, and parathormone (PTH) levels to rule out liver or bone disease as a cause for hyperphosphatasaemia. RESULTS: Of 15 patients 7 were male and 8 were female. Mean age was 2.45 ± 1.09 (range 1.2-4.6) years. Mean serum ALP level was 2315 ± 1028 IU/L (1102-4662), while liver enzymes, calcium, phosphate, PTH and vitamin D3 levels were in normal ranges. The mean normalization period of ALP was 2.4 ± 1.1 (0.5-4) months, and all were normal at the end of 4 months without any treatment. CONCLUSION: This study and literature knowledge related to BTH has shown that being aware of BTH is very important for a primary care physician. Paediatricians can conveniently manage the differential diagnosis and follow up this period of elevated ALP.