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.

Risk Factors and Clinical Characteristics of Metabolic Bone Disease of Prematurity.

OBJECTIVE: The study aimed to analyze the risk factors and clinical features of metabolic bone disease of prematurity (MBDP) in premature infants compared with infants of similar gestational age and birth weight without MBDP. STUDY DESIGN: This retrospective case-control study was performed by comparing 81 cases of MBDP with 63 controls to identify potential risk factors. Premature infants with a gestational age ≤33 weeks and birth weight <1,500 g were included. Medical records were examined in terms of maternal conditions, potential risk factors, and clinical characteristics. RESULTS: Bone fractures and invasive ventilator dependence were the most common clinical features of MBDP. Duration of invasive ventilation and total mechanical ventilation days, necrotizing enterocolitis, corticosteroid use, anticonvulsive drug use, duration of dexamethasone and caffeine use, total parenteral nutrition, and length of hospitalization were significantly higher in neonates with MBDP (p < 0.05). Breastfed neonates and those receiving human milk fortifier had a lower incidence of MBDP than those premature formula or mixed feeding (p < 0.05). Anticonvulsive drug use (odds ratio: 2.935; 95% confidence interval: 1.265-6.810) was identified as a risk factor for MBDP at multiple regression analysis. CONCLUSION: Our results show that anticonvulsive drug use is a significant risk factor for the development of MBDP. If long-term use is not required, anticonvulsive drugs should be stopped as soon as possible. Further studies involving patients with MBDP are required to determine the risk factors and clinical features. KEY POINTS: · MBDP is a multifactorial disorder.. · Anticonvulsive drug use is an important risk factor for the development of MBDP.. · Bone fractures and invasive ventilator dependence are the most common clinical features of MBDP..

Successful therapeutic plasma exchange in a case with extremely severe hypertriglyceridemia secondary to diabetic ketoacidosis concomitant with type IX glycogen storage disease.

Herein, we aimed to present a child with extremely severe hypertriglyceridemia (ESHTG) secondary to diabetic ketoacidosis concomitant with type IX glycogen storage disease (GSD). Extremely severe hypertriglyceridemia (10 700 mg/dL) was detected through the apparent lipemic appearance of the sampled blood in a 17-year-old male patient with severe diabetic ketoacidosis. In spite of insulin infusion, the patient's clinical condition deteriorated to acute pancreatitis. Single sessions of therapeutic plasma exchange (TPE) along with insulin treatment have successfully intercepted the progression of the state of acute pancreatitis. The patient was also diagnosed with type IX GSD on the basis of the genetic analyses performed for the potential underlying metabolic diseases. In conclusion, underlying metabolic diseases, such as glycogen storage disease, should be investigated in patients with diabetic ketoacidosis accompanied by severe hypertriglyceridemia. If ESHTG does not relieve despite insulin infusion, and/or acute pancreatitis occurs as a complication, TPE should be kept in mind.

Clinical, sonographical, and pathological findings of pediatric thyroid nodules.

Thyroid nodules are less frequent in children than in adults. A higher rate of malignancy is highlighted in this group. We aimed to analyze the clinical, laboratory, and ultrasound (US) findings of children and adolescents with benign and malignant thyroid nodules. This was a retrospective review of children and adolescents evaluated at a tertiary pediatric institution between 2007 and 2019. Patients with autonomously functioning nodules, autoimmune thyroid diseases, and a history of oncohematological disorders were excluded. A total of 102 patients with 131 nodules were identified. The study population included 57 females (55.9%); the average age was 10.6 ±4 years. Thirty-five nodules (26.7%) ranging 4.5-36 mm had a fine-needle aspiration (FNA) done: 45.7% (n = 16) were benign, 11.4% (n = 4) were classified as atypia, and 8.5% (n = 3) were consistent with papillary carcinoma. Fourteen patients (13.7%) underwent surgery. Five (4.9%) were finally diagnosed with papillary thyroid cancer. Of the 6 patients with benign FNAs, all except one, which was initially reported as atypia by an earlier FNA but was later diagnosed with papillary carcinoma, had a colloid nodular goiter. Of the 3 patients with atypia FNAs, one was found to be papillary carcinoma. One hundred twenty-five benign nodules (21 based on cytology and/or histology, 104 on clinical and imaging follow-up) were diagnosed. Nodule size, microcalcifications, solid parenchyma, and pathologic lymph node alterations were associated with malignancy, but nodule growth was not.Conclusion: Diagnostic approach and management of children with thyroid nodules should be based on a stepwise evaluation including clinical, laboratory, and US findings. Of the 102 patients identified, 4.9% had thyroid carcinoma below the range described in previous literature. What is Known: • Thyroid nodules are less frequent in children than in adults but more frequently malignant. Research on factors associated with malignancy have mostly been conducted in adults; further studies in pediatric thyroid nodules are warranted. What is New: • Microcalcifications, pathologic lymph node alterations, solid parenchyma, and larger nodule size are associated with malignant nodules, but nodule growth is not always suggestive of thyroid malignancy. The incidence of thyroid malignancy in this population was below the reported worldwide incidence in children with thyroid nodules.

Amitriptyline Intoxication in Children: Twenty Years' Experience in a Tertiary Care Center in Turkey.

BACKGROUND: Amitriptyline ingestion is an important cause of poisoning morbidity and mortality in Turkey and other countries. In contrast to adults, data concerning amitriptyline intoxication in children are limited. The purpose of this study was to investigate amitriptyline intoxication findings in the pediatric population, based on age groups and reported dosages. METHODS: The medical records of 192 patients admitted to the Karadeniz Technical University Medical Faculty Farabi Hospital Pediatric Emergency Department, Turkey, due to amitriptyline intoxication in 1997-2017 were examined retrospectively. Patients were divided into 6 groups based on amitriptyline doses and 4 groups based on age. Complete blood count, blood glucose, serum electrolytes, renal and liver function tests, coagulation tests (prothrombin time and partial thromboplastin time), and blood gas analysis were studied in all patients. Electrocardiography was performed on all children, and chest radiography and electroencephalography on those with respiratory or central nervous system symptoms. RESULTS: Amitriptyline intoxication was most frequently observed between the ages of 1 and 4 years. The most common signs and symptoms observed at time of hospital admission were lethargy and drowsiness (45.3%), sinus tachycardia (19.2%), and nausea and vomiting (13%). The most common laboratory finding was hyperglycemia (17.7). Six patients were intubated because of respiratory failure, and mechanical ventilation was initiated in these cases. One patient with amitriptyline overdose had persistent supraventricular tachycardia. Four children died due to amitriptyline intoxication. CONCLUSIONS: Tricyclic antidepressant intoxication is a leading cause of mortality and morbidity in children. It is therefore particularly important to identify the clinical and laboratory findings that develop with high-dose consumption.

Acute liver failure associated with metabolic diseases: A 10-year single-center experience.

BACKGROUND: Acute liver failure (ALF) is a rare multisystemic disease occurring in individuals with no history of liver disease, characterized by coagulopathy and / or hepatic encephalopathy secondary to acute liver injury. It is mostly caused by viral infections, drug intoxication, and metabolic diseases (MD), and can also have an indeterminate etiology. In this study, we aimed to evaluate the demographic and clinical characteristics and clinical outcomes of the patients that presented to our clinic with MD-associated ALF. METHODS: This retrospective study reviewed age, gender, parental consanguinity, family history, presence of encephalopathy, laboratory parameters, and clinical outcomes of the patients that presented to our clinic between January 2009 and January 2019. Patients with MD-associated ALF were compared with patients in whom ALF was associated with other etiologies. RESULTS: The study included 39 patients (53.8% boys; mean age + SD 6.13 ± 1.43 years). The total and direct bilirubin, international normalized ratio, and ammoniac levels were significantly higher in patients with MD than in the others (P < 0.05). Moreover, the incidences of hypoglycemia, death of a sibling and / or a family history of liver disease were also higher in patients with MD than in the others (P < 0.05). On the other hand, alanine aminotransferase (ALT) levels were significantly higher in patients with other etiologies. CONCLUSIONS: Metabolic diseases should be kept in mind in patients with a history of parental consanguinity and a positive family history of liver disease along with less increased alanine aminotransferase than expected, and increased bilirubin, international normalized ratio, and ammoniac levels and hypoglycemia. As the number of these parameters increases, the chance of diagnosis increases.

Seasonal vitamin D status of healthy schoolchildren and predictors of low vitamin D status.

OBJECTIVES: The aim of the study was to assess seasonal prevalence of vitamin D deficiency according to sex and to determine the relations between serum levels of 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) and sociodemographic characteristics in otherwise healthy schoolchildren during spring and autumn. METHODS: In a cross-sectional study, 746 healthy students aged between 11 and 18 years were recruited during spring (n = 375) and autumn (n = 371). Sociodemographic data were collected by a questionnaire. Serum 25(OH)D, PTH, calcium, phosphate, and alkaline phosphatase were measured. Serum 25(OH)D levels were categorized as <50 nmol/L (vitamin D deficiency) and <25 nmol/L (severe deficiency). RESULTS: Mean ± standard deviation 25(OH)D levels were 22.3 ± 10.5 nmol/L in girls and 28.5 ± 17.0 nmol/L in boys during spring (P < 0.001) and 36.5 ± 20.3 nmol/L in girls and 45.0 ± 18.5 nmol/L in boys during autumn (P < 0.001). The prevalence of vitamin D deficiency was 93% during spring and 71% during autumn. There was a negative correlation between 25(OH)D and PTH levels (P < 0.01). We determined a cutoff point of serum 25(OH)D in which the mean serum PTH concentration began to increase as 35.8 nmol/L (P < 0.0001). The age, sex, and calcium level were found to be independent predictors for vitamin D deficiency. CONCLUSIONS: Vitamin D deficiency is prevalent among healthy schoolchildren. It is noteworthy that 25(OH)D levels were significantly lower in girls and during autumn. We recommend vitamin D supplementation for children in addition to more time spent for outdoor activities for sensible sunlight exposure.

Role of ERα and Aromatase in Juvenile Gigantomastia.

CONTEXT: Approximately 150 patients with juvenile gigantomastia have been reported in the literature but the underlying biologic mechanisms remain unknown. OBJECTIVE: To conduct extensive clinical, biochemical, immunochemical, and genetic studies in 3 patients with juvenile gigantomastia to determine causative biologic factors. METHODS: We examined clinical effects of estrogen by blockading estrogen synthesis or its action. Breast tissue aromatase expression and activity were quantitated in 1 patient and 5 controls. Other biochemical markers, including estrogen receptor α (ERα), cyclin D1 and E, p-RB, p-MAPK, p-AKT, BCL-2, EGF-R, IGF-IR ß, and p-EGFR were assayed by Western blot. Immunohistochemical analyses for aromatase, ERα and ß, PgR, Ki67, sulfotransferase, estrone sulfatase, and 17ßHD were performed in all 3 patients. The entire genomes of the mother, father, and patient in the 3 families were sequenced. RESULTS: Blockade of estrogen synthesis or action in patients resulted in demonstrable clinical effects. Biochemical studies on fresh frozen tissue revealed no differences between patients and controls, presumably due to tissue dilution from the large proportion of stroma. However, immunohistochemical analysis of ductal breast cells in the 3 patients revealed a high percent of ERα (64.1% ± 7.8% vs reference women 9.6%, range 2.3-15%); aromatase score of 4 (76%-100% of cells positive vs 30.4% ± 5.6%); PgR (69.5% ± 15.2% vs 6.0%, range 2.7%-11.9%) and Ki67 (23.7% ± 0.54% vs 4.2%). Genetic studies were inconclusive although some intriguing variants were identified. CONCLUSION: The data implicate an important biologic role for ERα to increase tissue sensitivity to estrogen and aromatase to enhance local tissue production as biologic factors involved in juvenile gigantomastia.

A novel DAX-1 mutation presented with precocious puberty and hypogonadotropic hypogonadism in different members of a large pedigree.

Patients with DAX-1 gene mutations on chromosome Xp21 usually present with adrenal hypoplasia congenita and hypogonadotropic hypogonadism. Yet, neither correlation between the type of mutation and the age of onset of the disease nor mechanism of the mutation on puberty is fully understood. Here, we report a novel non-sense p.Gln208X mutation in the amino terminal domain of the DAX-1 gene observed in a large family with three boys presenting with adrenal manifestations at different ages. Furthermore, two boys developed spontaneous puberty that failed to progress at similar ages, whereas the other boy developed precocious puberty at 10 month of age. The unique structure of the DAX-1 gene may explain this phenotypic variability. However, more studies are needed to understand the role of the DAX-1 gene on development of the adrenal gland and hypothalamus-pituitary-gonadal axis.

De novo Pure Partial Trisomy 6p Associated with Facial Dysmorphism, Developmental Delay, Brain Anomalies, and Primary Congenital Hypothyroidism.

Introduction: Partial trisomy 6p is a rare chromosomal anomaly, characterized by low birth weight, developmental delay, craniofacial abnormalities, feeding difficulties, congenital heart defects, and renal abnormalities. Some of the partial trisomy 6p cases reported in the literature included partial monosomy of another chromosome. This is often due to the fact that one of the parents is a balanced translocation carrier, thereby making it difficult to determine the genotype-phenotype relationship. Pure partial trisomy 6p cases are even rarer and may occur as a result of a marker chromosome, tandem or inverted duplication, and interchromosomal insertion. Case Presentation: In this study, we evaluated the physical characteristics and genetic data of a 2-year-old girl with developmental delay and facial dysmorphic features. Dysmorphology assessment revealed the presence of a prominent forehead, short and narrow palpebral fissures, blepharoptosis, convex nasal ridge, hemangioma on the left eyelid, high-arched palate, retromicrognathia, and low-set ears. The patient‧s G-banded karyotype was 46,XX,der(2)t(2;6)(q37.3;p22.1). Upon SNP-array analysis, aimed to determine the origin of the extra chromosomal material detected in chromosome 2 of the patient, there was a de novo 27.5-Mb duplication at 6p, arr[GRCh37] 6p25.3p22.1(204,909_27,835,272)×3, interpreted to be pathogenic. Conclusion: We present this case report to clarify the clinical findings of a rare chromosomal anomaly, discuss the genes that may be related to the phenotype and contribute to the literature in terms of knowledge regarding genotype-phenotype correlation.

Intrathyroidal ectopic thymus: an important entity in the differential diagnosis of thyroid nodules.

BACKGROUND: Intrathyroidal ectopic thymus (IET), a benign lesion due to aberrant thymic migration during embryogenesis, is often discovered incidentally. We aimed to present the ultrasound (US) features, diagnostic methods, and follow-up of IET in children and adolescents. METHODS: We searched our database of patients with a nodular thyroid lesion detected by US, between January 2007 and December 2019. In 30/255 (11.7%), IET was diagnosed. RESULTS: The study included 30 patients (20 males/10 females), mean age 5 years (0.1-12.2, median 5.6) with 34 lesions diagnosed by US as `incidentalomas.` None of the patients had palpable nodules. On US, IET appeared as a hypoechoic lesion, with multiple punctuate internal echoes. 29/34 of lesions had well-defined margins. The most common location of IET was in the middle part (27/34) of the left lobe (19/34). The mean longest diameter at diagnosis was 6.4 mm (2.5-21, median 4.5). Sonographic follow-up was available in 25 patients with 27 lesions. The mean time of observation was 2.7 years (0.3-7.5, median 2.1). While 13/27 cases showed decreased size or regression during follow-up, the other 13 increased in size, and there was no change in size in one. Pubertal progression was associated with both increment and decrease in size of IET. Fine needle aspiration (FNA) was performed in 5 patients and surgery in one. CONCLUSIONS: IET should be considered in the differential diagnosis of pediatric thyroid nodules as a cause of FNA and/or surgery. Regular US monitoring can be used safely in the follow-up of this lesion. We present one of the largest series in the literature with long-term follow-up and description of patients` pubertal status. IET prevalence was 11.7% among children and adolescents with a nodular thyroid lesion, higher than that stated in the literature.

A Long-Term Comparison of Presenting Characteristics of Children with Newly Diagnosed Type 1 Diabetes Before and During the COVID-19 Pandemic

Objective: Diabetic ketoacidosis (DKA) - a potentially preventable complication of type 1 diabetes mellitus (T1D) - is one of the most common chronic childhood diseases, and is associated with a significant risk of morbidity and mortality. The limited use of healthcare services due to fear of Coronavirus disease-2019 (COVID-19) transmission during the pandemic has raised concerns of delays in T1D diagnosis, among other diseases. This study investigated the presenting characteristics of newly diagnosed T1D patients assessed in a single clinic during the pandemic and compares them with the pre-pandemic period. Methods: For the purpose of this study, the first year of the pandemic is referred to as the "pandemic period", and the previous three years as the "pre-pandemic period". Patient files were reviewed retrospectively, the demographic and clinical characteristics and laboratory findings of the patients were recorded, and the findings from both periods were compared. Results: The number of patients diagnosed with T1D in the pandemic period was 44, and in the pre-pandemic period 39 in 2017, 22 in 2018 and 18 in 2019. The two groups had similar age, sex, pubertal stage and anthropometric characteristics (p>0.05). Regarding the type of presentation, the frequency of DKA was significantly higher in the pandemic period (68.2%) than in the pre-pandemic period (40.5%) (p=0.006), and this difference was also observed in the comparison by years (p=0.016). The duration of symptoms (16.5±10.7 vs. 23.5±17.6 days) and the length of hospital stay (10±3.9 vs. 15.2±5.5 days) were significantly shorter in the pandemic period (p=0.032, and p<0.001, respectively). There was no difference in the frequency of severe DKA between the pandemic (46.7%) and the pre-pandemic (37.5%) periods (p>0.05). However, pH (7.17±0.16 vs. 7.26±0.14) and bicarbonate (12.8±6.3 vs. 16.6±6.3) levels were significantly lower in the pandemic period (p<0.005). Additional signs of infection on admission were less frequent in the pandemic period (9.1%) than in the pre-pandemic period (27.8%) (p=0.027). The groups did not differ in terms of hemoglobin A1c, C-peptide, concurrent thyroid autoantibodies and tissue transglutaminase antibodies (p>0.05). The rate of anti-glutamic acid decarboxylase positivity was higher in the pandemic period (73.8% vs. 39.2%) (p=0.001) while the frequency of other diabetes-associated autoantibodies was similar between the groups (p>0.05). The polymerase chain reaction test for COVID-19 was negative in six patients with a history of contact. Conclusion: There was an increased frequency and severity of DKA in children with newly diagnosed T1D in the pandemic period, and these findings justify concerns related to the diagnosis of other diseases during the pandemic. Studies to raise awareness of diabetes symptoms during the pandemic should be continued regularly to reach all segments of society. Our study provides an additional contribution to the literature in its coverage of the one-year period during the pandemic and its comparison with the previous three years.

Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked Syndrome in Two Siblings: Same Mutation But Different Clinical Manifestations at Onset

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is an early onset systemic autoimmune genetic disorder caused by mutation of the forkhead box protein 3 (FOXP3) gene. Enteropathy, endocrinopathy and skin manifestations are considered the classic triad of IPEX syndrome. However, patients with IPEX syndrome display a variety of phenotypes including life threatening multi-organ autoimmunity. Here, we present the case of two siblings with IPEX syndrome with the same hemizygous mutation, but with different types of symptomology at onset of the disease.

Increased Severe Cases and New-Onset Type 1 Diabetes Among Children Presenting With Diabetic Ketoacidosis During First Year of COVID-19 Pandemic in Turkey.

Introduction: There have been some significant changes regarding healthcare utilization during the COVID-19 pandemic. Majority of the reports about the impact of the COVID-19 pandemic on diabetes care are from the first wave of the pandemic. We aim to evaluate the potential effects of the COVID-19 pandemic on the severity of diabetic ketoacidosis (DKA) and new onset Type 1 diabetes presenting with DKA, and also evaluate children with DKA and acute COVID-19 infection. Methods: This is a retrospective multi-center study among 997 children and adolescents with type 1 diabetes who were admitted with DKA to 27 pediatric intensive care units in Turkey between the first year of pandemic and pre-pandemic year. Results: The percentage of children with new-onset Type 1 diabetes presenting with DKA was higher during the COVID-19 pandemic (p < 0.0001). The incidence of severe DKA was also higher during the COVID-19 pandemic (p < 0.0001) and also higher among children with new onset Type 1 diabetes (p < 0.0001). HbA1c levels, duration of insulin infusion, and length of PICU stay were significantly higher/longer during the pandemic period. Eleven patients tested positive for SARS-CoV-2, eight were positive for new onset Type 1 diabetes, and nine tested positive for severe DKA at admission. Discussion: The frequency of new onset of Type 1 diabetes and severe cases among children with DKA during the first year of the COVID-19 pandemic. Furthermore, the cause of the increased severe presentation might be related to restrictions related to the pandemic; however, need to evaluate the potential effects of SARS-CoV-2 on the increased percentage of new onset Type 1 diabetes.

The effects of antiepileptic drugs on the relationships between leptin levels and bone turnover in prepubertal children with epilepsy.

Antiepileptic drugs (AED) had an effect on bone metabolism in children. This study was conducted in order to determine the relationships between serum leptin levels, bone mineral density (BMD) and bone turnover markers in epileptic children. Fifty-three patients were treated with valproic acid (VPA) and 23 with carbamazepine (CBZ) monotherapy; 50 healthy children were included in the study as controls. Serum alkaline phosphatase (ALP) and cross-linked C-telopeptide (CTx) levels were statistically significantly higher in the CBZ group than in the VPA group and the control group (p < 0.0001, p < 0.010, respectively). Serum osteocalcin and ALP levels were significantly lower in the VPA group than in the control group (P < 0.012, P < 0.030, respectively). Although we found slightly higher serum leptin levels in both the CBZ and VPA groups, they were not significantly different from the control group (P > 0.05). We demonstrated that the markers of bone formation and resorption increased with CBZ and decreased with VPA treatment without affecting BMD and vitamin D levels in prepubertal epileptic children.

Two sisters with Bardet-Biedl syndrome: brain abnormalities and unusual facial findings.

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with a wide spectrum of clinical manifestations. BBS is predominantly characterized by dysmorphic distal extremities, obesity, structural abnormalities or functional impairment of the kidney, rod cone dystrophy, and varying degrees of mental retardation. Hypogenitalism is also present, only in males, and in all cases, facial similarities. We present herein two sisters with BBS, one of whom also had cerebellar vermis hypoplasia and cerebral and cerebellar atrophy, and both of whom had ocular abnormalities in the form of epicanthus and telecanthus and metabolic syndrome. It should also be emphasized that the occurrence of cerebellar involvement such as cerebellar vermis hypoplasia and cerebellar atrophy in BBS is very unusual. The association of abnormalities in brain development and other facial features in children with BBS is not seen frequently; thus, these abnormalities should be searched carefully.

Partial remission in children and adolescents with type 1 diabetes: an analysis based on the insulin dose-adjusted hemoglobin A1c.

OBJECTIVES: Most patients with type 1 diabetes (T1D) experience a transient phase of partial remission (PR). This study aimed to identify the demographic and clinical factors associated with PR. METHODS: This was a longitudinal retrospective cohort study of 133 children and adolescents with T1D. PR was defined by the gold standard insulin dose-adjusted hemoglobin A1c (HbA1c) (IDAA1c) of ≤9. RESULTS: Remission was observed in 77 (57.9%) patients. At diagnosis, remitters had significantly higher pH (7.3 ± 0.12 vs. 7.23 ± 0.15, p=0.003), higher C-peptide levels (0.45 ± 0.31 ng/mL vs. 0.3 ± 0.22, p=0.003), and they were significantly older (9.3 ± 3.6 years vs. 7.3 ± 4.2, p=0.008) compared with non-remitters. PR developed more frequently in patients without diabetic ketoacidosis (DKA) (p=0.026) and with disease onset after age 5 (p=0.001). Patients using multiple daily insulin regimen were more likely to experience PR than those treated with a twice daily regimen (63.9 vs. 32%, p=0.004). Only age at onset was an independent predictor of PR (OR: 1.12, 95% CI: 1-1.25; p=0.044). Remitters had lower HbA1c levels and daily insulin requirement from diagnosis until one year after diagnosis (p<0.001). PR recurred in 7 (9%) patients. The daily insulin requirement at three months was lower in remitters with PR recurrence compared to those without (0.23 ± 0.14 vs. 0.4 ± 0.17 U/kg/day, p=0.014). CONCLUSIONS: Addressing factors associated with the occurrence of PR could provide a better comprehension of metabolic control in T1D. The lack of DKA and higher C-peptide levels may influence PR, but the main factor associated with PR presence was older age at onset. PR may recur in a small proportion of patients.

Corticosteroid-induced sinus bradycardia in a young boy with adrenal insufficiency and sepsis. / Bradicardia sinusal inducida por corticoesteroides en un niño con insuficiencia suprarrenal y septicemia.

The literature does not commonly describe cardiac rhythm disturbances, including bradycardia, in patients who are receiving corticosteroids, and the exact mechanism of such disturbances remains unknown. Herein, we present a case of sinus bradycardia associated with stress-dose corticosteroid therapy. A nine-year-old boy with a history of panhypopituitarism was admitted with gastroenteritis and pneumonia and developed septic shock on the day of admission. Management using intravenous fluids, stress doses of hydrocortisone, and antibiotics resulted in full recovery. However, within 24 hours following treatment, sinus bradycardia was documented, with a heart rate of 45 beats per minute (BPM). The bradycardia resolved after the dose of hydrocortisone was decreased gradually. Corticosteroidinduced sinus bradycardia is an adverse effect that usually resolves after corticosteroid treatment is discontinued. During stress-dose corticosteroid therapy, hemodynamic monitoring should be considered. To our knowledge, this is the first report of sinus bradycardia following the use of hydrocortisone in children who have adrenal insufficiency.

La bibliografía no incluye frecuentemente alteraciones en el ritmo cardíaco de los pacientes que reciben corticoesteroides; se desconoce su mecanismo exacto. En este artículo, presentamos el caso de un paciente con bradicardia sinusal asociada con una dosis de estrés de corticoesteroides. Se ingresó a un niño de 9 años con antecedentes de panhipopituitarismo con gastroenteritis y neumonía y presentó choque septicémico el día de la hospitalización. El tratamiento con líquidos intravenosos, dosis de estrés de hidrocortisona y antibióticos permitió la recuperación. Sin embargo, luego se documentó bradicardia sinusal con una frecuencia cardíaca de 45 latidos por minuto. Esta se resolvió después de reducir gradualmente la hidrocortisona. La bradicardia sinusal inducida por corticoesteroides es un efecto adverso que suele resolverse tras interrumpir el tratamiento. Se debe considerar el monitoreo hemodinámico en estos casos. Este es el primer informe de bradicardia sinusal posterior al uso de hidrocortisona en niños con insuficiencia suprarrenal.