Prevalence and risk factors associated with low bone mineral density in Asian adolescents with anorexia nervosa and atypical anorexia nervosa.

OBJECTIVE: This retrospective study aimed to evaluate the prevalence and risk factors for low bone mineral density (BMD) at diagnosis in Asian adolescent females with anorexia nervosa (AN) and atypical AN. METHOD: We analyzed the BMD results for 213 patients between 10 and 18 years of age, with AN and atypical AN receiving care at a pediatric hospital in Singapore. We used linear regression analyses to determine if type of eating disorder, premorbid weight, and duration of amenorrhea were risk factors for low BMD. For a subset of patients with repeat BMD evaluation, we used paired t-tests to assess the impact of weight or menstrual restoration on the change in BMD. RESULTS: The prevalence of BMD height-for-age Z-scores <-2 at presentation was higher in patients with AN (13.0%) than atypical AN (2.3%) (p = .034). In multivariate regression, a diagnosis of atypical AN was protective against low BMD at the lumbar spine (B = 0.394, p = .009) and total body less head (B = 0.774, p = .010). Duration of amenorrhea was not associated with BMD across all sites. For those with repeat BMD measures, there was significantly less deterioration in the BMD Z-scores for patients with weight or menstrual restoration (R = -0.22 ± 0.59, NR = -0.69 ± 0.43, p = .029). CONCLUSIONS: Duration of amenorrhea was not associated with BMD in this sample. A diagnosis of AN was correlated with lower BMD than atypical AN. Further research is needed to better understand the relationship between amenorrhea, weight status, and bone health in Asian adolescents with eating disorders. PUBLIC SIGNIFICANCE: In this sample, 13% of Asian adolescents with AN and 2.3% of Asian adolescents with atypical AN have low BMD. In our study population, duration of amenorrhea was not correlated with BMD. Among adolescents with AN, a history of being underweight at the highest pre-morbid BMI, is correlated with low BMD. It is important for physicians to take a thorough weight history in evaluating bone health in this population.

Early Puberty Trend during the COVID-19 Pandemic in Singapore: A Retrospective Review in a Single Tertiary Centre.

Objectives: We aimed to study the trend of referrals for precocious puberty during the COVID-19 pandemic compared to pre-COVID years, explore the differences in the demographic and clinical features, and evaluate the contributing factors. Methodology: The cases referred for assessment of PP from 2018-2021 to our endocrine centre were grouped into pre-COVID (2018-2019) and COVID (2020-2021) years. Cases fulfilling the diagnosis of PP included the onset of thelarche <8 years in females and 4 ml testicular volume <9 years in males. The PP was further differentiated as Isolated Thelarche (IST) and Central Precocious Puberty (CPP). Early menarche was defined as menarche <10 years old. Results: There were more referrals for PP and more diagnosed as CPP during the COVID-19 pandemic, predominantly among females. There were more endocrine tests done and more cases received treatment. None of the abnormal magnetic resonance imaging (MRI) pituitary findings required surgical intervention. The body mass index (BMI) was found to be positively associated with the risk of getting CPP with a crude-odd ratio (COR) of 1.8, P <0.001, and early menarche (COR 2.1, P <0.001). Conclusion: We found a significant increase in the referrals of PP and diagnosis of CPP during the COVID-19 pandemic. Higher BMI was found to be associated with CPP and early menarche.

Paediatric Obesity Evaluation for Metabolic Susceptibility (POEMS).

INTRODUCTION: Our aim was to determine whether there are risk factors which increase the risk of developing dysglycemia in a child who has increased body mass index (BMI) (overweight/obese). RESEARCH DESIGN AND METHODS: This was a retrospective cohort study of 715 children who had increased BMI (overweight/obese). They presented to tertiary care at KK Women's and Children's Hospital, Singapore, for metabolic risk assessment. Subjects who had more than one oral glucose tolerance test were included in order to track and analyze risk factors associated with worsening glycemic status from a previously normal glucose tolerance, impaired fasting glucose, or impaired glucose tolerance (IGT) state. Demographic characteristics, birth history, family history of metabolic syndrome, metabolic comorbidities, and interventions received were recorded. Statistical analysis was performed to determine odds ratio (OR) of worsening glycemic status progression in association with an analyzed variable, adjusted for intervention received. RESULTS: Risk factors of developing dysglycemia can be present right from birth, as participants who were born preterm had increased odds of IGT (OR: 3.49 (1.10 to 11.03)), and a greater proportion of large-for-gestational-age (LGA)/small-for-gestational-age (SGA) babies had dysglycemia (SGA-IGT: 8.8%, SGA-diabetes mellitus (DM): 5.9%, LGA-IGT: 10.6%, LGA-DM: 11.8%) even at baseline. Being born preterm (OR: 3.49 (1.10 to 11.03)), with comorbidities of hypertension (OR: 1.61 (1.01 to 2.57)), hyperlipidemia (OR: 1.80 (1.19 to 2.72)), and fatty liver disease (OR: 2.08 (1.39 to 3.13)), was significantly associated with an increased OR of developing IGT. Risk factors for developing a worsening glycemic status, either to IGT or DM, included age >10 years (OR 4.94 (1.21 to 20.25)), BMI rise (OR 1.71 (1.17 to 2.49)), BMI increase >1.08 kg/m2 (OR 1.71 (1.16 to 2.51)), comorbidities of hyperlipidemia (OR 1.67 (1.12 to 2.50)), and fatty liver disease (OR 2.11 (1.43 to 3.12)). CONCLUSIONS: A child who has increased BMI (overweight/obese) and possesses risk factors for worsening glycemic status, if intervened with routine lifestyle modification advice, may still have increased risk of developing dysglycemia and type 2 DM. Therefore, understanding their risk profile provides opportunities to have a tiered and individualized approach.

Evaluation of risk factors associated with fragility fractures and recommendations to optimise bone health in children with long-term neurological condition.

Introduction: The growing years are paramount for bone growth and mineral accrual. Children with long-term neurological condition (LTNC) have multiple risk factors for poor bone health and fragility fractures. In Singapore, this has not been studied systematically. Therefore, we aimed to evaluate the risk factors associated with fragility fractures in children with LTNC. Methods: In this study, the search for fragility fractures was done by a retrospective review of patients with LTNC on follow-up in the paediatric neurology clinic and patients who presented with fracture to the paediatric orthopaedic clinic. Information on patients' demographics, medical history, intervention, biochemical bone markers and fracture history was collected. Results: In a tertiary clinic population of 136 patients with LTNC, 65% were dependent on mobility (Gross Motor Function Classification System [GMFCS] V), 60% were underweight and 60% were fed via gastrostomy or nasogastric tube, or were on oral pureed diet. Furthermore, 60% were on anticonvulsants. The fracture rate was 3% in this population and was associated with low-impact activities such as transfer and dressing. Only 7.4% and 33% of the patients had undergone measurements of vitamin D and calcium levels, respectively. Conclusion: The local prevalence of fragility fractures in children with LTNC on follow-up at the neurology clinic was found to be 3%. Risk factors identified were limited ambulation and compromised nutritional status associated with feeding difficulty. Recommendations to optimise bone health in children with LTNC were made. These include promoting weight-bearing activities, looking out for underweight children, avoiding vitamin D deficiency and ensuring adequate calcium intake.

Patent ductus arteriosus in a late preterm neonate: think congenital hypopituitarism.

A late preterm female neonate presented with initial respiratory distress and heart murmur attributed to a haemodynamically significant patent ductus arteriosus (hsPDA) not responding to two courses of ibuprofen. Thyroid function performed for prolonged neonatal jaundice at 3 weeks of life suggested central hypothyroidism. Subsequent adrenocorticotropic hormone stimulation test showing hypocortisolism and MRI revealing adenohypophysis hypoplasia confirmed the diagnosis of congenital hypopituitarism (CH). Commencement of hydrocortisone followed by thyroxine replacement coincided with clinical closure of the hsPDA within 72 hours of treatment. Hypothyroidism and hypocortisolism may have contributed to persistent hsPDA. Thyroid hormone increases cytochrome P450 activity, endothelin-1 and fibronectin expression. Hydrocortisone decreases sensitivity of ductus arteriosus to PGE2 These mechanisms have been postulated to cause ductal constriction and closure. Our case supports this association. hsPDA in a term and near-term neonate with a protracted disease course or associated midline defects should prompt the clinician to suspect CH (hypothyroidism and/or hypocortisolism).

MIRAGE Syndrome Caused by a De Novo c.3406G>C (p. Glu1136Gln) Mutation in the SAMD9 Gene Presenting With Neonatal Adrenal Insufficiency and Recurrent Intussusception: A Case Report.

Introduction: Primary adrenal insufficiency (PAI) presenting in the neonatal period can be life threatening and requires early recognition, diagnosis, and management. PAI due to adrenal hypoplasia (syndromic/non-syndromic) is a rare disorder. MIRAGE is a recently described syndrome with PAI and multisystem involvement. Case Presentation: A preterm female neonate presenting with PAI and persistent severe thrombocytopenia was diagnosed to have MIRAGE syndrome due to a de novo pathogenic variant c.3406G>C (p. Glu1136Gln) in the SAMD9 gene. In the first year of life, she had recurrent respiratory and gastrointestinal infection causing failure to thrive. At 17 months, she suffered recurrent intussusception requiring treatment with parenteral nutrition and high-dose steroids. Subsequently, she established oral feeds with hydrolysed formula and demonstrated good weight gain. Conclusion: In neonates presenting with PAI and associated multisystem involvement, a thoughtful approach and genetic testing is valuable in discerning an etiological diagnosis. This case of MIRAGE adds to the spectrum of reported cases and is the first to report on recurrent intussusception and its management with high-dose steroids.

Further delineation of CDC45-related Meier-Gorlin syndrome with craniosynostosis and review of literature.

Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by the triad of short stature, microtia and absent or small patellae. We report on a patient with MGS secondary to biallelic mutations in CDC45 detected on whole exome sequencing (WES). Patients with MGS caused by mutations in CDC45 display a distinct phenotype characterized by craniosynostosis and anorectal malformation. Our patient had craniosynostosis, anorectal malformation and short stature, but did not have the microtia or patella hypoplasia. Our report also highlights the value of WES in aiding diagnosis of patients with rare genetic diseases. In conclusion, our case report and review of the literature illustrates the unique features of CDC45-related MGS as well as the benefits of WES in reducing the diagnostic odyssey for patients with rare genetic disorders.

A novel Ser40Trp variant in IFITM5 in a family with osteogenesis imperfecta and review of the literature.

Osteogenesis imperfecta, is a genetically and clinically heterogeneous connective tissue disorder that disrupts bone architecture, making it fragile and more prone to fractures. While more than 85% of cases are due to variants in COL1A1 and COL1A2, variants in noncollagen genes have been identified in the remaining cases. The recurring heterozygous variant in IFITM5 (c.-14C>T) leads to osteogenesis imperfecta type V, a second missense variant in IFITM5 (c.119C>T, p.Ser40Leu) leads to phenotype resembling osteogenesis imperfecta type VI. In this report, we describe the first patient with Ser40Trp variant in IFITM5, who presented with multiple fractures in the prenatal period. She remained fracture free after birth (except for trauma-related fractures during puberty) with normal bone mineral densitometry. Her mother, who did not have a history of fracture, was noted to have somatogonadal mosaicism for this variant and became pregnant with a second child with multiple prenatal fractures, found to have the same variant. To our knowledge, this is the first case of somatogonadal mosaicism in IFITM5. In addition, we have summarized the literature on patients presenting with variant in codon 40 (serine) of IFTIM5 protein.

Ultrasound-guided measurement of skin and subcutaneous tissue thickness in children with diabetes and recommendations for giving insulin injections.

AIM: To measure skin thickness (ST) and skin + subcutaneous layer thickness (SCT) by ultrasound and estimate the risk of intramuscular injection (IM) with different needle lengths across injection sites according to age group. METHOD: Children recruited between 1 and 18 years with type 1 and 2 diabetes on insulin injections and divided into three age groups: 1-6 years, 7-12 years and 13-18 years. A portable ultrasound was used to measure ST and SCT at four injection sites on the abdomen, arm, thigh and buttock. RESULTS: Total 153 children enrolled for the study. The mean (SD) measurement of ST & SCT at four sites on abdomen, arm, thigh & buttocks were as follows; 4.33 mm (±2.22), 5.55 mm (±2.26), 5.83 mm (±3.12), 6.48 mm (±3.47) in 1-6 years old; 7.11 mm (±3.68), 7.79 mm (±4.54), 7.17 mm (±3.62), 8.51 mm (±3.65) in 7-12 years old; 8.94 mm (±4.50), 8.42 mm (±5.00), 8.61 mm (±4.76), 9.76 mm (±4.38) in 13-18 years old. Young children, 1-6 years have the highest risk of IM injection with all needle lengths, i.e. 4, 5, 6, 8 & 12.7 mm, while older children 7-12 & 13-18 years have a lower risk with shorter needles (4, 5 and 6 mm) as compared to longer needles (8 and 12.7 mm). CONCLUSIONS: Children with diabetes on insulin therapy should be advised on the appropriate needle length accordingly to their age and BMI.

Primary osteoporosis in children.

Osteoporosis in childhood is uncommon, and it may be secondary to a spectrum of diverse conditions. Idiopathic juvenile osteoporosis is a primary osteoporosis of unknown aetiology present in previously well children and is a diagnosis of exclusion. We describe a 10-year-old prepubertal boy who presented with back pain of 1-week duration. His spinal X-ray showed generalised loss of vertebral body heights in keeping with osteoporosis. Endocrine and haematological work-up were normal. He was treated with vitamin D supplement and intravenous pamidronate. This case illustrates the general work-up and causes for paediatric osteoporosis, and the management for idiopathic juvenile osteoporosis.