Primary adrenal insufficiency in a patient with biallelic QRSL1 mutations

Dursun, Fatma; Genç, Hülya Maraş; Yılmaz, Ayşe Mine; Taş, İbrahim; Eser, Mehmet; Pehlivanoğlu, Cemile; Yılmaz, Baran; Güran, Tülay

doi:10.1530/eje-22-0233

Cited by 3 publications

(5 citation statements)

References 9 publications

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“…Nine reports link adrenal insufficiency with point mutations that impair ETC complex activity ( Table 1 ) [ 4 , 63 , 64 , 65 ]. The age of adrenal insufficiency varied (7 days to 16 years) and it was always part of a syndromic picture dominated by other organ-system derangement [ 64 ].…”

Section: Literature Review Resultsmentioning

confidence: 99%

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Adrenal Dysfunction in Mitochondrial Diseases

Corkery-Hayward

Metherell

2023

IJMS

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Cortisol is central to several homeostatic mechanisms including the stress and immune response. Adrenal insufficiency and impaired cortisol production leads to severe, potentially fatal disorders. Several fundamental stages of steroidogenesis occur within the mitochondria. These dynamic organelles not only contribute ATP for steroidogenesis, but also detoxify harmful by-products generated during cortisol synthesis (reactive oxygen species). Mutations in nuclear or mitochondrial DNA that impair mitochondrial function lead to debilitating multi-system diseases. Recently, genetic variants that impair mitochondrial function have been identified in people with isolated cortisol insufficiency. This review aimed to clarify the association between mitochondrial diseases and adrenal insufficiency to produce cortisol. Mitochondrial diseases are rare and mitochondrial diseases that feature adrenal insufficiency are even rarer. We identified only 14 cases of adrenal insufficiency in people with confirmed mitochondrial diseases globally. In line with previous reviews, adrenal dysfunction was most prevalent in mitochondrial deletion syndromes (particularly Pearson syndrome and Kearns–Sayre syndrome) and with point mutations that compromised oxidative phosphorylation. Although adrenal insufficiency has been reported with mitochondrial diseases, the incidence reflects that expected in the general population. Thus, it is unlikely that mitochondrial mutations alone are responsible for an insufficiency to produce cortisol. More research is needed into the pathogenesis of adrenal disease in these individuals.

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Section: Literature Review Resultsmentioning

confidence: 99%

“…Similarly, Endres et al uncovered a MT-ND4 variant that led to ETC complex 1 subunit malformation [ 47 ]. Dursun et al uncovered a novel biallelic QRSL1 mutation that decreased the activity of ETC Complexes I, II, IV, and V [ 65 ]. The increased oxidative stress and mitochondrial damage may have resulted in their patient’s severe PAI.…”

Section: Discussionmentioning

confidence: 99%

Adrenal Dysfunction in Mitochondrial Diseases

Corkery-Hayward

Metherell

2023

IJMS

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Section: Resultsmentioning

confidence: 99%

“…61 The case of an 8-year-old boy with AD and multiple somatic complications represents the longest survival with QRSL1 mutation underlying mitochondrial combined oxidative phosphorylation deficiency-40; Dursun et al reported a novel biallelic mutation -c.300T>A;Y100* and c.610G>A;G204R. 62 One family with 3 brothers carrying a novel NNT (nicotinamide nucleotide transhydrogenase) mutation (biallelic pathogenic variant, homozygous for c.1575dup) was reported with AD in the oldest brothers. 63 Also, we mention here a large study on patients with Down syndrome (N = 6078 versus 30,326 controls) over a 28-year period of time that evaluated 21 endocrine conditions, including AD which was found with a higher prevalence based on OR of 1.68 (95% CI: 1.18-2.4).…”

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confidence: 99%

Addison’s Disease: Diagnosis and Management Strategies

Cârșote¹,

Nistor²

2023

IJGM

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We aim to overview Addison’s disease (AD) with regard to current diagnosis and management. This is a narrative review of full-length articles published in English between January 2022 and December 2022 (including online ahead of print versions) in PubMed-indexed journals. We included original studies in living humans regardless of the level of statistical significance starting from the key search terms “Addison’s disease” or “primary adrenal insufficiency” in title or abstract. We excluded articles with secondary adrenal insufficiency. Briefly, 199 and 355 papers, respectively were identified; we manually checked each of them, excluded the duplicates, and then selected 129 based on their clinical relevance in order to address our 1-year analysis. We organized the data in different subsections covering all published aspects on the subject of AD. To our knowledge, this is the largest AD retrospective from 2022 on published data. A massive role of genetic diagnosis especially in pediatric cases is highlighted; the importance of both pediatric and adult awareness remains since unusual presentations continue to be described. COVID-19 infection is a strong player amid this third year of pandemic although we still not do have large cohorts in this particular matter as seen, for instance, in thyroid anomalies. In our opinion, the most important topic for research is immune checkpoint inhibitors, which cause a large panel of endocrine side effects, AD being one of them.

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“…The QRSL1 product enables glutaminyl-tRNA synthase (glutamine-hydrolyzing) activity in the mitochondria. Missense mutations in the human QRSL1 locus have been associated with defects in mitochondrial respiratory chain complex and oxidative phosphorylation ( 45, 46 ). The resulting oxidative stress enhances lipogenesis ( 47, 48 ).…”

Section: Supplementary Informationmentioning

confidence: 99%

Cryptococcosis, tuberculosis, and a kidney cancer fail to fit the atherosclerosis paradigm for foam cell lipid content

Guerrini

Prideaux

Khan

et al. 2023

Preprint

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Foam cells are dysfunctional, lipid-laden macrophages associated with chronic inflammation of infectious and non-infectious origin. For decades, the paradigm of foam cell biology has been atherogenesis, in which macrophages accumulate cholesteryl esters. Our previous work showed that foam cells in tuberculous lung lesions are surprisingly triglyceride-rich, suggesting multiple modalities of foam cell biogenesis. In the present study, we used matrix-assisted laser desorption/ionization mass spectrometry imaging to assess the spatial distribution of storage lipids relative to foam-cell-rich areas in murine lungs infected with the fungal pathogen Cryptococcus neoformans and in human papillary renal cell carcinoma resection tissues. We also analyzed neutral lipid content and the transcriptional program of lipid-laden macrophages generated under corresponding in vitro conditions. The in vivo data were consistent with in vitro findings showing that C. neoformans-infected macrophages accumulated triglycerides, while macrophages exposed to human renal cell carcinoma-conditioned medium accumulated both triglycerides and cholesteryl esters. Moreover, macrophage transcriptome analyses provided evidence for condition-specific metabolic remodeling. The in vitro data also showed that although both Mycobacterium tuberculosis and C. neoformans infections induced triglyceride accumulation in macrophages, they did so by different molecular mechanisms, as evidenced by different sensitivity of lipid accumulation to the drug rapamycin and the characteristics of macrophage transcriptome remodeling. Collectively, these data demonstrate that the mechanisms of foam cell formation are specific to the disease microenvironment. Since foam cells have been regarded as targets of pharmacological intervention in several diseases, recognizing that their formation is disease-specific opens new research directions of biomedical significance.

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Primary adrenal insufficiency in a patient with biallelic QRSL1 mutations

Cited by 3 publications

References 9 publications

Adrenal Dysfunction in Mitochondrial Diseases

Adrenal Dysfunction in Mitochondrial Diseases

Addison’s Disease: Diagnosis and Management Strategies

Cryptococcosis, tuberculosis, and a kidney cancer fail to fit the atherosclerosis paradigm for foam cell lipid content

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