Delayed puberty is defined as the absence of physical signs of puberty 2 to 2.5 standard deviations above the mean age and affects approximately 2% of adolescents. Causes of delayed puberty are broadly divided into two categories: hypergonadotropic hypogonadism and hypogonadotropic hypogonadism. One exception to this classification system is constitutional delay of growth and puberty, the most common cause of delayed puberty. For the general pediatrician, knowledge of the different causes and initial steps to evaluation is crucial when a patient with delayed puberty presents. [Pediatr Ann. 2018;47(1):e16-e22.].

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Background: Multisystem inflammatory syndrome in children (MIS-C) is a serious inflammatory response to a prior coronavirus disease of 2019 (COVID-19), characterized by fever, inflammation, and multiorgan dysfunction. Current literature does not indicate a relationship between pediatric diabetes and risk of developing MIS-C. Here, we report a case of pediatric type 2 diabetes (T2D) with diabetic ketoacidosis (DKA) and severe multi-organ dysfunction with SARS-CoV-2 serology positivity. Clinical Case: A 13-year-old African American female with obesity (Body Mass Index >99th %) and poorly controlled T2D (HbA1c 12.8%) presented to the emergency department for one week of sore throat, headache, and abdominal pain. SARS-CoV-2 positivity was confirmed by PCR. The next day, she was found unconscious at home. She was diagnosed with DKA and was directly admitted to the pediatric intensive care unit. IV insulin and aggressive fluid resuscitation were initiated and her DKA resolved over the next 72 hrs. However, she exhibited continued altered mental status with slurred speech and significant respiratory distress requiring respiratory support. Due to the severe presentation and multi-organ involvement, a multi-disciplinary care team was formed. Further workup confirmed acute respiratory distress syndrome with pneumonia; severe acute kidney injury (AKI, creatinine of 4.56 mg/dL); presumed myocarditis (ST elevation on EKG, troponin 4.47 ng/mL, BNP 129.8 pg/mL); punctuate intraparenchymal hemorrhage in the splenium of the corpus callosum; transaminitis (AST 188 u/L, ALT 100 u/L); pancreatitis (amylase 651 u/L, lipase >9500 u/L); thrombocytopenia with consumptive coagulopathy (platelet 81 X 103/µL, d-dimer 5.91 mcg FEU/mL), increased inflammatory markers (ESR 53 mm/hr, ferritin 127 ng/mL), and positive SARS-CoV-2 serology. A presumed diagnosis of MIS-C was made per the Centers for Disease Control and Prevention definition and she was started on dexamethasone and intravenous immunoglobulin (IVIG). While consideration was given to the possibility of acute COVID-19 infection in combination with DKA, she was not a candidate for remdesivir due to AKI. On day 12, she developed new dysarthria, dyspraxia and behavioral changes. Encephalopathy workup was negative (CSF Encephalopathy autoimmune panel negative, NMDA receptor negative) and she was restarted on dexamethasone and IVIG. She was discharged on day 28. Conclusion: There is a paucity of literature of MIS-C associated with COVID-19 in the pediatric diabetes. Our case highlights several novel aspects of MIS-C with concurrent poorly controlled diabetes and DKA, including severe central nervous system manifestations and prolonged hospitalization. Further studies are warranted to elucidate an association between pediatric diabetes and MIS-C and to develop guidelines for management of MIS-C in poorly controlled pediatric diabetes.

Background: Allan-Herndon-Dudley (AHD) is a rare X-linked disorder with neurological manifestations secondary to a mutation in monocarboxylate transporter 8, a protein that transports T3 into nerve cells in the brain. AHD is characterized by increased serum free T3, decreased serum free T4 and normal serum TSH levels as well as the severe neurological manifestations including global developmental delay, hypotonia, and joint contractures (1). A phase 2 trial using triodyothyroacetic acid has shown promise in treating this disorder (2). We report on three children who were diagnosed by whole exome sequencing after presenting with neurological manifestations. Clinical Cases: Patient 1 presented at 4 months to the neurology clinic for seizures. He had a normal newborn screen. Worsening developmental delays and central hypotonia prompted a brain MRI that revealed delayed myelination for age. At 6 months a chromosomal microarray and metabolic work-up were performed and were nondiagnostic. Whole exome sequencing was obtained at the age of 4.5 years revealing a mutation in the SLC16A2 gene (p.Ser210Tyr). Thyroid studies were consistent with the diagnosis. Patient 2 presented to neurology at 9 months for developmental delay. A brain MRI was obtained which was within normal limits. At 14 months an acylcarnitine profile was obtained which indicated a possible CPT1 deficiency, which did not fit his clinical picture. Chromosomal microarray as well as work-up for inborn errors of metabolism were performed and were nondiagnostic. Thyroid studies were obtained which showed low free T4 with normal TSH. Whole exome sequencing was obtained at the age of 2.5 years, which revealed a mutation in SLC16A2 (p.R371C). Patient 3 presented as sibling of patient 2 with known AHD syndrome. Testing for SLC16A2 was performed at the age of 5 months and returned positive for same mutation as sibling (p.R371C). Conclusion: Allan-Herndon-Dudley syndrome is a rare neurological disease secondary to a mutation in the T3 transporter protein to nervous tissue. A high index of suspicion as well as thyroid studies should be obtained in patients presenting with central hypotonia and global developmental delay with normal newborn screens, particularly in states that use TSH as a screening test. This is especially important as treatments are becoming available that may help prevent neurological devastation seen in these patients. References: 1. Dumitrescu AM, Fu J, Dempsey MA, Refetoff S. MCT8-Specific Thyroid Hormone Cell-Membrane Transporter Deficiency. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993 2. Groeneweg S, Peeters RP, Moran C, et al. Effectiveness and safety of the tri-iodothyronine analogue Triac in children and adults with MCT8 deficiency: an international, single-arm, open-label, phase 2 trial. Lancet Diabetes Endocrinol. 2019;7(9):695-706.