Long-Term Follow-up of a Case with Proprotein Convertase 1/3 Deficiency: Transient Diabetes Mellitus with Intervening Diabetic Ketoacidosis During Growth Hormone Therapy

Overview

Journal J Clin Res Pediatr Endocrinol

Specialties Endocrinology
Pediatrics

Date 2017 Jun 8

PMID 28588004

Citations 6

Authors

E Nazli Gonc

Alev Ozon

Ayfer Alikasifoglu

Nurgun Kandemir

Affiliations

Soon will be listed here.

Abstract

Proprotein convertase 1/3 (PC1/3) deficiency is a very rare disease characterized by severe intractable diarrhea in the first years of life, followed by obesity and several hormonal deficiencies later. Diabetes mellitus requiring insulin treatment and diabetic ketoacidosis have not been reported in this disorder. We herein present a girl with PC1/3 deficiency who has been followed from birth to 17 years of age. She developed deficiencies of all pituitary hormones over time as well as diabetes mellitus while receiving growth hormone (GH) therapy. She was complicated with diabetic ketoacidosis during dietary management of diabetes mellitus, thus insulin treatment was initiated. Insulin requirement to regulate hyperglycemia was short-lived. Repeat oral glucose tolerance test five years later was normal. The findings of this patient show that diabetes mellitus can develop at any time during follow-up of cases with proportein convertase 1/3 deficiency especially under GH therapy.

Citing Articles

PROPROTEIN CONVERTASE 1/3 DEFICIENCY WITH PELVIC EWING SARCOMA.

Oral H, Guven D, Ozdemir D, Usubutun A, Gonc N, Arik Z Acta Endocrinol (Buchar). 2023; 18(4):508-511.

PMID: 37152885 PMC: 10162823. DOI: 10.4183/aeb.2022.508.

Modulation of PC1/3 activity by a rare double-site homozygous mutation.

Ni Y, Chen X, Sun Y, Pan J, Tang C, Yuan T Front Pediatr. 2022; 10:1026707.

PMID: 36389395 PMC: 9659753. DOI: 10.3389/fped.2022.1026707.

Rare Heterozygous Variants in Human Obesity: The Contribution of the p.Y181H Variant and a Literature Review.

Van Dijck E, Beckers S, Diels S, Huybrechts T, Verrijken A, Van Hoorenbeeck K Genes (Basel). 2022; 13(10).

PMID: 36292633 PMC: 9601648. DOI: 10.3390/genes13101746.

Islet MC4R Regulates PC1/3 to Improve Insulin Secretion in T2DM Mice via the cAMP and β-arrestin-1 Pathways.

Ni Z, Wang Y, Shi C, Zhang X, Gong H, Dong Y Appl Biochem Biotechnol. 2022; 194(12):6164-6178.

PMID: 35900711 DOI: 10.1007/s12010-022-04089-y.

A case of prohormone convertase deficiency diagnosed with type 2 diabetes.

Karacan Kucukali G, Savas Erdeve S, Cetinkaya S, Keskin M, Bulus A, Aycan Z Turk Arch Pediatr. 2021; 56(1):81-84.

PMID: 34013237 PMC: 8114606. DOI: 10.14744/TurkPediatriArs.2020.36459.

References

Bandsma R, Sokollik C, Chami R, Cutz E, Brubaker P, Hamilton J . From diarrhea to obesity in prohormone convertase 1/3 deficiency: age-dependent clinical, pathologic, and enteroendocrine characteristics. J Clin Gastroenterol. 2013; 47(10):834-43. PMC: 3842618. DOI: 10.1097/MCG.0b013e3182a89fc8. View

Wilschanski M, Abbasi M, Blanco E, Lindberg I, Yourshaw M, Zangen D . A novel familial mutation in the PCSK1 gene that alters the oxyanion hole residue of proprotein convertase 1/3 and impairs its enzymatic activity. PLoS One. 2014; 9(10):e108878. PMC: 4182778. DOI: 10.1371/journal.pone.0108878. View

Seidah N . The proprotein convertases, 20 years later. Methods Mol Biol. 2011; 768:23-57. DOI: 10.1007/978-1-61779-204-5_3. View

Dosi R, Patell R, Shah P, Joshi H . Diabetic ketoacidosis: an unusual presentation of acromegaly. BMJ Case Rep. 2013; 2013. PMC: 3702944. DOI: 10.1136/bcr-2013-010198. View

ORahilly S, Gray H, Humphreys P, Krook A, Polonsky K, White A . Brief report: impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function. N Engl J Med. 1995; 333(21):1386-90. DOI: 10.1056/NEJM199511233332104. View

Martin M, Lindberg I, Solorzano-Vargas R, Wang J, Avitzur Y, Bandsma R . Congenital proprotein convertase 1/3 deficiency causes malabsorptive diarrhea and other endocrinopathies in a pediatric cohort. Gastroenterology. 2013; 145(1):138-148. PMC: 3719133. DOI: 10.1053/j.gastro.2013.03.048. View

Palakawong P, Arakaki R . Diabetic Ketoacidosis in Acromegaly: A Case Report. Endocr Pract. 2012; :1-15. DOI: 10.4158/EP12189.CR. View

Yigit S, Estrada E, Bucci K, Hyams J, Rosengren S . Diabetic ketoacidosis secondary to growth hormone treatment in a boy with Prader-Willi syndrome and steatohepatitis. J Pediatr Endocrinol Metab. 2004; 17(3):361-4. DOI: 10.1515/jpem.2004.17.3.361. View

Jackson R, Creemers J, Ohagi S, Raffin-Sanson M, Sanders L, Montague C . Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet. 1997; 16(3):303-6. DOI: 10.1038/ng0797-303. View

10.

Farooqi I, Volders K, Stanhope R, Heuschkel R, White A, Lank E . Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3. J Clin Endocrinol Metab. 2007; 92(9):3369-73. DOI: 10.1210/jc.2007-0687. View

11.

Schaner P, Todd R, Seidah N, Nillni E . Processing of prothyrotropin-releasing hormone by the family of prohormone convertases. J Biol Chem. 1997; 272(32):19958-68. DOI: 10.1074/jbc.272.32.19958. View

12.

Fathallah N, Slim R, Larif S, Hmouda H, Ben Salem C . Drug-Induced Hyperglycaemia and Diabetes. Drug Saf. 2015; 38(12):1153-68. DOI: 10.1007/s40264-015-0339-z. View

13.

Frank G, Fox J, Candela N, Jovanovic Z, Bochukova E, Levine J . Severe obesity and diabetes insipidus in a patient with PCSK1 deficiency. Mol Genet Metab. 2013; 110(1-2):191-4. PMC: 3759845. DOI: 10.1016/j.ymgme.2013.04.005. View

14.

Erem C, Ersoz H, Ukinc K, Avunduk A, Hacihasanoglu A, Kocak M . Acromegaly presenting with diabetic ketoacidosis, associated with retinitis pigmentosa and octreotide-induced bradycardia: a case report and a review of the literature. Endocrine. 2006; 30(1):145-9. DOI: 10.1385/ENDO:30:1:145. View

15.

Gonc E, Kandemir N, Kinik S . Significance of low-dose and standard-dose ACTH tests compared to overnight metyrapone test in the diagnosis of adrenal insufficiency in childhood. Horm Res. 2003; 60(4):191-7. DOI: 10.1159/000073232. View