Startseite Sirolimus therapy in a patient with severe hyperinsulinaemic hypoglycaemia due to a compound heterozygous ABCC8 gene mutation
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Sirolimus therapy in a patient with severe hyperinsulinaemic hypoglycaemia due to a compound heterozygous ABCC8 gene mutation

  • Pratik Shah , Ved Bhushan Arya , Sarah E. Flanagan , Kate Morgan , Sian Ellard , Senthil Senniappan und Khalid Hussain EMAIL logo
Veröffentlicht/Copyright: 17. Dezember 2014
Journal of Pediatric Endocrinology and Metabolism
Aus der Zeitschrift Journal of Pediatric Endocrinology and Metabolism Band 28 Heft 5-6

Abstract

Introduction: Hyperinsulinaemic hypoglycaemia (HH) is the most common cause of severe and persistent hypoglycaemia in neonates. The treatment of severe diazoxide unresponsive HH involves near total pancreatectomy. Mammalian target of rapamycin (mTOR) is a protein kinase that regulates cellular proliferation. mTOR inhibitors are used in cancer patients and recently found to be effective in the treatment of insulinoma and HH patients.

Case: A 36 weeks large for gestational age neonate presented with severe hypoglycaemia on day 1 of life. The hypoglycaemia screen confirmed HH and genetic testing revealed compound heterozygous ABCC8 mutation, confirming diffuse disease. He was unresponsive to the maximal dose of diazoxide (15 mg/kg/day), hence needed treatment with higher concentration of intravenous glucose (25 mg/kg/min), intravenous glucagon and subcutaneous octreotide (30 μg/kg/day) infusions to maintain normoglycaemia. Sirolimus, a mTOR inhibitor, was commenced at 9 weeks of age following which he showed a marked improvement in his glycaemic control. After 4 weeks of sirolimus therapy, he was discharged home on subcutaneous octreotide injection (20 μg/kg/day) and oral sirolimus, thereby avoiding the need for a near total pancreatectomy.

Conclusion: We report the first case of compound heterozygous ABCC8 mutation causing severe diffuse HH that responded to therapy with a mTOR inhibitor.

Keywords: hyperinsulinaemic hypoglycaemia; mTOR; sirolimus
Corresponding author: Khalid Hussain, Developmental Endocrinology Research Group, Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, UK, Phone: +44-(0)20-7-905-2128, Fax: +44-(0)20-7-404-6191, E-mail:
aESPE membership: Khalid Hussain

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Received: 2014-8-31
Accepted: 2014-10-22
Published Online: 2014-12-17
Published in Print: 2015-5-1

©2015 by De Gruyter

Artikel in diesem Heft

  1. Frontmatter
  2. Highlight: Obesity
  3. Childhood obesity at the crossroads
  4. Obesogenic environments: environmental approaches to obesity prevention
  5. Childhood obesity and eating behaviour
  6. Hypothalamic obesity in children: pathophysiology to clinical management
  7. The reliability of body mass index in the diagnosis of obesity and metabolic risk in children
  8. Determining abdominal obesity cut-offs and relevant risk factors for anthropometric indices in Turkish children and adolescents
  9. The effect of body mass index on blood pressure varies by race among obese children
  10. Insulin secretion response during oral glucose tolerance test is related to low cardiorespiratory fitness in obese adolescents
  11. Is there a relationship between cardiovascular risk factors and dehydroepiandrosterone sulfate levels in childhood obesity?
  12. The effect of lifestyle change and metformin therapy on serum arylesterase and paraoxonase activity in obese children
  13. Childhood obesity, thyroid function, and insulin resistance – is there a link? A longitudinal study
  14. Associations between IGF-I, IGF-binding proteins and bone turnover markers in prepubertal obese children
  15. Osteocalcin is inversely associated with adiposity and leptin in adolescent boys
  16. Association between cardiovascular risk factors and carotid intima-media thickness in prepubertal Brazilian children
  17. Insulin resistance and cardiometabolic risk factors in obese children and adolescents: a hierarchical approach
  18. The role of apolipoprotein E polymorphism in improving dyslipidemia in obese adolescents following physical exercise and National Cholesterol Education Program Step II intervention
  19. Review article
  20. Is ultrasound useful in the diagnosis of adolescents with polycystic ovary syndrome?
  21. Original articles
  22. IGF-II expression and methylation in small for gestational age infants
  23. Early screening of FTO and MC4R variants in newborns of Greek origin
  24. Pitfalls in hormonal diagnosis of 17-beta hydroxysteroid dehydrogenase III deficiency
  25. The prevalence of vitamin D deficiency among schoolchildren: a cohort study from Xinxiang, China
  26. Management of testosterone therapy in adolescents and young men with hypogonadism: are we following adult clinical practice guidelines?
  27. Vitamin D status and its associations with components of metabolic syndrome in healthy children
  28. Metformin treatment improves weight and dyslipidemia in children with metabolic syndrome
  29. Patient reports
  30. Hypothyroidism caused by the combination of two heterozygous mutations: one in the TSH receptor gene the other in the DUOX2 gene
  31. Ovarian carcinoma in a 14-year-old with classical salt-wasting congenital adrenal hyperplasia and bilateral adrenalectomy
  32. An asymptomatic mother diagnosed with 3-methylcrotonyl-CoA carboxylase deficiency after newborn screening
  33. A new missense mutation in the BCKDHB gene causes the classic form of maple syrup urine disease (MSUD)
  34. Ovotesticular disorder of sex development with unusual karyotype: patient report
  35. First case report of medium-chain acyl-coenzyme A dehydrogenase deficiency in China
  36. Virilizing adrenal oncocytoma in a 9-year-old girl: rare neoplasm with an intriguing postoperative course
  37. Unexpected clinical features in a female patient with proopiomelanocortin (POMC) deficiency
  38. Sirolimus therapy in a patient with severe hyperinsulinaemic hypoglycaemia due to a compound heterozygous ABCC8 gene mutation
  39. Cross-reactivity of adrenal steroids with aldosterone may prevent the accurate diagnosis of congenital adrenal hyperplasia
  40. Hyperthyroidism hidden by congenital central hypoventilation syndrome
  41. The use of pamidronate for acute vitamin D intoxication, clinical experience with three cases
  42. Chondrocalcinosis related to familial hypomagnesemia with hypercalciuria and nephrocalcinosis
  43. Cushing syndrome related to leukemic infiltration of the central nervous system
  44. Hashimoto’s encephalopathy: a rare pediatric brain disease
  45. Short communication
  46. A novel ABCD1 gene mutation in a Chinese patient with X-linked adrenoleukodystrophy
https://doi.org/10.1515/jpem-2014-0371
Schlagwörter für diesen Artikel
hyperinsulinaemic hypoglycaemia; mTOR; sirolimus

Artikel in diesem Heft

  1. Frontmatter
  2. Highlight: Obesity
  3. Childhood obesity at the crossroads
  4. Obesogenic environments: environmental approaches to obesity prevention
  5. Childhood obesity and eating behaviour
  6. Hypothalamic obesity in children: pathophysiology to clinical management
  7. The reliability of body mass index in the diagnosis of obesity and metabolic risk in children
  8. Determining abdominal obesity cut-offs and relevant risk factors for anthropometric indices in Turkish children and adolescents
  9. The effect of body mass index on blood pressure varies by race among obese children
  10. Insulin secretion response during oral glucose tolerance test is related to low cardiorespiratory fitness in obese adolescents
  11. Is there a relationship between cardiovascular risk factors and dehydroepiandrosterone sulfate levels in childhood obesity?
  12. The effect of lifestyle change and metformin therapy on serum arylesterase and paraoxonase activity in obese children
  13. Childhood obesity, thyroid function, and insulin resistance – is there a link? A longitudinal study
  14. Associations between IGF-I, IGF-binding proteins and bone turnover markers in prepubertal obese children
  15. Osteocalcin is inversely associated with adiposity and leptin in adolescent boys
  16. Association between cardiovascular risk factors and carotid intima-media thickness in prepubertal Brazilian children
  17. Insulin resistance and cardiometabolic risk factors in obese children and adolescents: a hierarchical approach
  18. The role of apolipoprotein E polymorphism in improving dyslipidemia in obese adolescents following physical exercise and National Cholesterol Education Program Step II intervention
  19. Review article
  20. Is ultrasound useful in the diagnosis of adolescents with polycystic ovary syndrome?
  21. Original articles
  22. IGF-II expression and methylation in small for gestational age infants
  23. Early screening of FTO and MC4R variants in newborns of Greek origin
  24. Pitfalls in hormonal diagnosis of 17-beta hydroxysteroid dehydrogenase III deficiency
  25. The prevalence of vitamin D deficiency among schoolchildren: a cohort study from Xinxiang, China
  26. Management of testosterone therapy in adolescents and young men with hypogonadism: are we following adult clinical practice guidelines?
  27. Vitamin D status and its associations with components of metabolic syndrome in healthy children
  28. Metformin treatment improves weight and dyslipidemia in children with metabolic syndrome
  29. Patient reports
  30. Hypothyroidism caused by the combination of two heterozygous mutations: one in the TSH receptor gene the other in the DUOX2 gene
  31. Ovarian carcinoma in a 14-year-old with classical salt-wasting congenital adrenal hyperplasia and bilateral adrenalectomy
  32. An asymptomatic mother diagnosed with 3-methylcrotonyl-CoA carboxylase deficiency after newborn screening
  33. A new missense mutation in the BCKDHB gene causes the classic form of maple syrup urine disease (MSUD)
  34. Ovotesticular disorder of sex development with unusual karyotype: patient report
  35. First case report of medium-chain acyl-coenzyme A dehydrogenase deficiency in China
  36. Virilizing adrenal oncocytoma in a 9-year-old girl: rare neoplasm with an intriguing postoperative course
  37. Unexpected clinical features in a female patient with proopiomelanocortin (POMC) deficiency
  38. Sirolimus therapy in a patient with severe hyperinsulinaemic hypoglycaemia due to a compound heterozygous ABCC8 gene mutation
  39. Cross-reactivity of adrenal steroids with aldosterone may prevent the accurate diagnosis of congenital adrenal hyperplasia
  40. Hyperthyroidism hidden by congenital central hypoventilation syndrome
  41. The use of pamidronate for acute vitamin D intoxication, clinical experience with three cases
  42. Chondrocalcinosis related to familial hypomagnesemia with hypercalciuria and nephrocalcinosis
  43. Cushing syndrome related to leukemic infiltration of the central nervous system
  44. Hashimoto’s encephalopathy: a rare pediatric brain disease
  45. Short communication
  46. A novel ABCD1 gene mutation in a Chinese patient with X-linked adrenoleukodystrophy
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