Browse

You are looking at 1 - 10 of 81 items for :

  • Adolescent/young adult x
Clear All
Open access

Raku Son, Masahiko Nagahama, Fumiaki Tanemoto, Yugo Ito, Fumika Taki, Ryosuke Tsugitomi and Masaaki Nakayama

Summary

The etiology of hyponatremia is assessed based on urine osmolality and sodium. We herein describe a 35-year-old Asian man with pulmonary tuberculosis and perforated duodenal ulcer who presented with hyponatremia with hourly fluctuating urine osmolality ranging from 100 to 600 mosmol/kg, which resembled urine osmolality observed in typical polydipsia and SIADH simultaneously. Further review revealed correlation of body temperature and urine osmolality. Since fever is a known non-osmotic stimulus of ADH secretion, we theorized that hyponatremia in this patient was due to transient ADH secretion due to fever. In our case, empiric exogenous glucocorticoid suppressed transient non-osmotic ADH secretion and urine osmolality showed highly variable concentrations. Transient ADH secretion-related hyponatremia may be underrecognized due to occasional empiric glucocorticoid administration in patients with critical illnesses. Repeatedly monitoring of urine chemistries and interpretation of urine chemistries with careful review of non-osmotic stimuli of ADH including fever is crucial in recognition of this etiology.

Learning points:

  • Hourly fluctuations in urine osmolality can be observed in patients with fever, which is a non-osmotic stimulant of ADH secretion.
  • Repeated monitoring of urine chemistries aids in the diagnosis of the etiology underlying hyponatremia, including fever, in patients with transient ADH secretion.
  • Glucocorticoid administration suppresses ADH secretion and improves hyponatremia even in the absence of adrenal insufficiency; the etiology of hyponatremia should be determined carefully in these patients.
Open access

Sara Lomelino-Pinheiro, Bastos Margarida and Adriana de Sousa Lages

Summary

Familial hypomagnesemia with secondary hypocalcemia (FHSH) is a rare autosomal recessive disorder (OMIM# 602014) characterized by profound hypomagnesemia associated with hypocalcemia. It is caused by mutations in the gene encoding transient receptor potential cation channel member 6 (TRPM6). It usually presents with neurological symptoms in the first months of life. We report a case of a neonate presenting with recurrent seizures and severe hypomagnesemia. The genetic testing revealed a novel variant in the TRPM6 gene. The patient has been treated with high-dose magnesium supplementation, remaining asymptomatic and without neurological sequelae until adulthood. Early diagnosis and treatment are important to prevent irreversible neurological damage.

Learning points:

  • Loss-of-function mutations of TRPM6 are associated with FHSH.
  • FHSH should be considered in any child with refractory hypocalcemic seizures, especially in cases with serum magnesium levels as low as 0.2 mM.
  • Normocalcemia and relief of clinical symptoms can be assured by administration of high doses of magnesium.
  • Untreated, the disorder may be fatal or may result in irreversible neurological damage.
Open access

Baris Akinci, Rasimcan Meral, Diana Rus, Rita Hench, Adam H Neidert, Frank DiPaola, Maria Westerhoff, Simeon I Taylor and Elif A Oral

Summary

A patient with atypical partial lipodystrophy who had a transient initial response to metreleptin experienced acute worsening of her metabolic state when neutralizing antibodies against metreleptin appeared. Because her metabolic status continued to deteriorate, a therapeutic trial with melanocortin-4 receptor agonist setmelanotide, that is believed to function downstream from leptin receptor in the leptin signaling system, was undertaken in an effort to improve her metabolic status for the first time in a patient with lipodystrophy. To achieve this, a compassionate use (investigational new drug application; IND) was initiated (NCT03262610). Glucose control, body fat by dual-energy X-ray absorptiometry and MRI, and liver fat by proton density fat fraction were monitored. Daily hunger scores were assessed by patient filled questionnaires. Although there was a slight decrease in hunger scales and visceral fat, stimulating melanocortin-4 receptor by setmelanotide did not result in any other metabolic benefit such as improvement of hypertriglyceridemia or diabetes control as desired. Targeting melanocortin-4 receptor to regulate energy metabolism in this setting was not sufficient to obtain a significant metabolic benefit. However, complex features of our case make it difficult to generalize these observations to all cases of lipodystrophy. It is still possible that melanocortin-4 receptor agonistic action may offer some therapeutic benefits in leptin-deficient patients.

Learning points:

  • A patient with atypical lipodystrophy with an initial benefit with metreleptin therapy developed neutralizing antibodies to metreleptin (Nab-leptin), which led to substantial worsening in metabolic control. The neutralizing activity in her serum persisted for longer than 3 years.
  • Whether the worsening in her metabolic state was truly caused by the development of Nab-leptin cannot be fully ascertained, but there was a temporal relationship. The experience noted in our patient at least raises the possibility for concern for substantial metabolic worsening upon emergence and persistence of Nab-leptin. Further studies of cases where Nab-leptin is detected and better assay systems to detect and characterize Nab-leptin are needed.
  • The use of setmelanotide, a selective MC4R agonist targeting specific neurons downstream from the leptin receptor activation, was not effective in restoring metabolic control in this complex patient with presumed diminished leptin action due to Nab-leptin.
  • Although stimulating the MC4R pathway was not sufficient to obtain a significant metabolic benefit in lowering triglycerides and helping with her insulin resistance as was noted with metreleptin earlier, there was a mild reduction in reported food intake and appetite.
  • Complex features of our case make it difficult to generalize our observation to all leptin-deficient patients. It is possible that some leptin-deficient patients (especially those who need primarily control of food intake) may still theoretically benefit from MC4R agonistic action, and further studies in carefully selected patients may help to tease out the differential pathways of metabolic regulation by the complex network of leptin signaling system.
Open access

Janani Devaraja, Charlotte Elder and Adrian Scott

Summary

This case report describes a family pedigree of a mother and her children with an E227K mutation in the KCNJ11 gene. People with this particular gene mutation typically present with transient neonatal diabetes; with more than half the cohort relapsing into permanent diabetes in adolescence or early adulthood. However, the mother developed diabetes as an adolescent and thus was initially diagnosed as having Type 1 Diabetes. All her children have inherited the same genetic mutation but with differing presentations. Her second, third and fourth child presented with transient neonatal diabetes which remitted at varying times. Her first child is 16 years old but had not developed diabetes at the time of writing. The KCNJ11 gene codes for the KIR6.2 subunit of the KATP channels of the pancreatic beta cells. Mutations in this gene limit insulin release from beta cells despite high blood glucose concentrations. Most people with diabetes caused by this genetic mutation can be successfully managed with glibenclamide. Learning of the genetic mutation changed the therapeutic approach to the mother’s diabetes and enabled rapid diagnosis for her children. Through this family, we identified that an identical genetic mutation does not necessarily lead to the same diabetic phenotype. We recommend clinicians to consider screening for this gene in their patients whom MODY is suspected; especially in those presenting before the age of 25 who remain C-peptide positive.

Learning points:

  • KATP channel closure in pancreatic beta cells is a critical step in stimulating insulin release. Mutations in the KIR6.2 subunit can result in the KATP channels remaining open, limiting insulin release.
  • People with KCNJ11 mutations may not present with neonatal diabetes as the age of presentation of diabetes can be highly variable.
  • Most affected individuals can be treated successfully with glibenclamide, which closes the KATP channels via an independent mechanism.
  • All first degree relatives of the index case should be offered genetic testing, including asymptomatic individuals. Offspring of affected individuals should be monitored for neonatal diabetes from birth.
  • Affected individuals will require long-term follow-up as there is a high risk of recurrence in later life.
Open access