Leucine-sensitive hyperinsulinaemic hypoglycaemia in patients with loss of function mutations in 3-Hydroxyacyl-CoA Dehydrogenase.

Orphanet Journal of Rare Diseases
Amanda J HeslegraveK Hussain

Abstract

Loss of function mutations in 3-Hydroxyacyl-CoA Dehydrogenase (HADH) cause protein sensitive hyperinsulinaemic hypoglycaemia (HH). HADH encodes short chain 3-hydroxacyl-CoA dehydrogenase, an enzyme that catalyses the penultimate reaction in mitochondrial β-oxidation of fatty acids. Mutations in GLUD1 encoding glutamate dehydrogenase, also cause protein sensitive HH (due to leucine sensitivity). Reports suggest a protein-protein interaction between HADH and GDH. This study was undertaken in order to understand the mechanism of protein sensitivity in patients with HADH mutations. An oral leucine tolerance test was conducted in controls and nine patients with HADH mutations. Basal GDH activity and the effect of GTP were determined in lymphoblast homogenates from 4 patients and 3 controls. Immunoprecipitation was conducted in patient and control lymphoblasts to investigate protein interactions. Patients demonstrated severe HH (glucose range 1.7-3.2 mmol/l; insulin range 4.8-63.8 mU/l) in response to the oral leucine load, this HH was not observed in control patients subjected to the same leucine load. Basal GDH activity and half maximal inhibitory concentration of GTP was similar in patients and controls. HADH protein could be co-i...Continue Reading

References

Aug 15, 2001·The Journal of Clinical Endocrinology and Metabolism·A KellyC A Stanley
May 5, 2005·The Journal of Pediatrics·Khalid HussainSimon Eaton
Nov 27, 2007·Biochemical and Biophysical Research Communications·Charlotta FillingUdo Oppermann
Mar 25, 2010·American Journal of Physiology. Endocrinology and Metabolism·Jason R TrebergJohn T Brosnan

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Citations

Jan 1, 2013·The Journal of Clinical Endocrinology and Metabolism·K E SniderA Ganguly
Apr 12, 2016·Frontiers in Endocrinology·Azizun NessaKhalid Hussain
Mar 4, 2015·Journal of Molecular Endocrinology·Sofia A RahmanKhalid Hussain
Apr 29, 2015·Journal of Pediatric Endocrinology & Metabolism : JPEM·Omer BabikerSenthil Senniappan
Sep 1, 2017·International Journal of Pediatric Endocrinology·Huseyin DemirbilekKhalid Hussain
May 12, 2018·Current Opinion in Pediatrics·Mary Ellen Vajravelu, Diva D De León
Sep 22, 2021·Journal of Pediatric Endocrinology & Metabolism : JPEM·Dinesh GiriSenthil Senniappan

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Methods Mentioned

BETA
deamination
electrophoresis

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