Acta Diabetologica

, Volume 50, Issue 6, pp 951–957 | Cite as

Six cases with severe insulin resistance (SIR) associated with mutations of insulin receptor: Is a Bartter-like syndrome a feature of congenital SIR?

  • Valeria Grasso
  • Carlo Colombo
  • Valeria Favalli
  • Alfonso Galderisi
  • Ivana Rabbone
  • Sara Gombos
  • Enzo Bonora
  • Ornella Massa
  • Franco Meschi
  • Franco Cerutti
  • Dario Iafusco
  • Riccardo Bonfanti
  • Carla Monciotti
  • Fabrizio Barbetti
Original Article

Abstract

Biallelic insulin receptor (INSR) gene mutations cause congenital syndromes of severe insulin resistance (SIR) known as Donohue syndrome (DS) and Rabson–Mendenhall syndrome (RMS). At presentation, DS and RMS are difficult to differentiate since they share many clinical features; however, while patients with DS usually die within 1 year of birth, individuals classified as RMS can reach adult age. INSR mutations can be also found in pubertal females with hyperinsulinism, hyperandrogenism, and acanthosis nigricans (type A SIR). We studied the INSR gene in five subjects with congenital SIR and in a patient with type A SIR. Nine biallelic INSR gene mutations (eight novels, including an in-frame deletion of INSR signal peptide) were identified in patients with congenital SIR; a heterozygous, spontaneous INSR mutation was detected in the patient with type A SIR. Two probands, presenting severe hirsutism at birth, died at the age of 3 months and were classified as DS, while other 2, currently 2 and 3 years old, were diagnosed with RMS (patients 3 and 4). The fifth patient with congenital SIR died when 14 months old. Nephrocalcinosis, hyperaldosteronism, hyperreninemia, and hypokalemia, in the absence of hypertension, were discovered in patients 3 and 5 when 24 and 4 months old, respectively. Patient 3, now 3 years/3 months old, still shows hyperreninemic hyperaldosteronism requiring potassium supplementation. We conclude that renal abnormalities resembling antenatal Bartter’s syndrome type II, recently reported also by others, is a common observation in patients with congenital SIR.

Keywords

Extreme insulin resistance Insulin receptor Mutation Bartter’s syndrome 

Notes

Acknowledgments

We thank the patients’ parents and relatives who participated in this study.

Conflict of interest

None.

Supplementary material

592_2013_490_MOESM1_ESM.xls (24 kb)
Supplementary material 1 (XLS 24 kb)

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Copyright information

© Springer-Verlag Italia 2013

Authors and Affiliations

  • Valeria Grasso
    • 1
  • Carlo Colombo
    • 2
  • Valeria Favalli
    • 3
  • Alfonso Galderisi
    • 4
  • Ivana Rabbone
    • 5
  • Sara Gombos
    • 6
  • Enzo Bonora
    • 7
  • Ornella Massa
    • 1
  • Franco Meschi
    • 3
  • Franco Cerutti
    • 5
  • Dario Iafusco
    • 8
  • Riccardo Bonfanti
    • 3
  • Carla Monciotti
    • 4
  • Fabrizio Barbetti
    • 1
    • 2
  1. 1.Laboratory of Mendelian DiabetesBambino Gesù Childrens’ HospitalRomeItaly
  2. 2.Department of Experimental Medicine and SurgeryUniversity of Tor VergataRomeItaly
  3. 3.Diabetes Unit, Pediatric ClinicH S Raffaele Scientific InstituteMilanItaly
  4. 4.Department of Women and Children’s HealthUniversity of PaduaPaduaItaly
  5. 5.Department of PediatricsUniversity of TurinTurinItaly
  6. 6.Neonatology and Neonatal Intensive Care Unit, Department of EmergencySantobono Pausillipon HospitalNaplesItaly
  7. 7.Division of Endocrinology, Diabetes and Metabolic DiseasesUniversity and Hospital Trust of VeronaVeronaItaly
  8. 8.Department of PediatricsSecond University of NaplesNaplesItaly

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