SFEIES24 Poster Presentations Adrenal & Cardiovascular (40 abstracts)
Adrenal insufficiency associated with mutations in haem biosynthesis genes, is it a coincidence?
Ahmed Al-Salihi 1 , Chris Smith 1 , Adam Jackson 2 , Andreas Janecke 3 , Elisabeth Steichen 3 , Denise Darby 2 , Liezel Griffin 4 , Siddharth Banka 2 , Solaf Elsayed 5 , Neila Talbi 6 , Laurent Gouya 6 , Brigitte Delemer 7 , Li Chan 1 & Louise Metherell 1
1Queen Mary University of London, London, United Kingdom; 2University of Manchester, Manchester, United Kingdom; 3University Hospital of Innsbruck, Innsbruck, Austria; 4Dermatology Centre, Salford Royal Hospital, Manchester, United Kingdom; 5Medical Genetics Department, Ain Shams University, Cairo, Egypt; 6The National Institute of Health and Medical Research (INSERM), Paris, France; 7Centre Hospitalier Universitaire De Reims, Reims, France
Primary adrenal insufficiency (PAI) is associated with mutations in more than 25 genes, in our cohort, most commonly the melanocortin receptor gene (MC2R), its accessory protein (MRAP), steroidogenic enzymes (STAR and CYP11A1), and a gene involved in mitochondrial anti-oxidant defence (NNT). While mutations in haem biosynthesis genes have only ever been implicated as pathogenic in a group of diseases known as porphyria, over the years, tantalising case reports have linked the two conditions. We found 7 families (11 individuals) with defects in haem biosynthetic enzymes that have flagrant AI with or without porphyria; 1) a kindred (n = 4) from Egypt with biallelic mutations in the protoporphyrinogen oxidase (PPOX) gene p.(Glu339Lys), who have a spectrum of symptoms ranging from failure to thrive, focal neurology, cutaneous lesions of variegate porphyria along with severe AI. 2) Three kindreds with mutations in coproporphyrinogen oxidase (CPOX), (i) a preterm female of Asian descent homozygous for p.(Pro367Ala) mutation, who presented with anaemia, jaundice, focal neurology and cutaneous manifestations of Hereditary Coproporphyria (HCP) along with AI, (ii) siblings of Kurdish descent homozygous for p.(Ser28*) mutation, the boy had HCP along with AI and Disorder of Sex Development, while the girl has no clinical manifestations of HCP but has severe AI, and (iii) a patient with HCP from France who presented with AI aged 64, this patient had a urinary steroid metabolome that showed elevated levels of 11-deoxycorticosterone and 11-deoxycortisol. 3) Three adult patients with mutations in Hydroxymethylbilane Synthase (HMBS) gene who presented with AI during acute hepatic porphyria attacks. The evidence linking mutations in porphyria genes with PAI is ever-growing suggesting that testing adrenal function might be beneficial for these patients and that the causal genes should be considered for inclusion in gene panels for AI.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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