Aldosterone Synthase Deficiency Type 2

Abstract Context Isolated congenital hypoaldosteronism presents in early infancy with symptoms including vomiting, severe dehydration, salt wasting, and failure to thrive. The main causes of this rare autosomal recessive disorder is pathogenic variants of the CYP11B2 gene leading to aldosterone synthase deficiency. Objective To investigate the presence of CYP11B2 pathogenic variants in a cohort of patients with a clinical, biochemical, and hormonal profile suggestive of aldosterone synthase deficiency. Design Clinical and molecular study. Setting Tertiary academic Children’s Hospital, Center for Rare Pediatric Endocrine Diseases. Patients and Methods Sixty-two patients (56 unrelated patients and 6 siblings), with hypoaldosteronism and their parents, underwent CYP11B2 gene sequencing after its selective amplification against the highly homologous CYP11B1 gene. In silico analysis of the identified novel variants was carried out to evaluate protein stability and potential pathogenicity. Results CYP11B2 gene sequencing revealed that 62 patients carried a total of 12 different pathogenic CYP11B2 gene variants, 6 of which are novel. Importantly, 96% of the 56 patients carried the previously reported p.T185I variant either in homozygosity or in compound heterozygosity with another variant. The 6 novel variants detected were: p.M1I, p.V129M, p.R141Q, p.A165T, p.R448C, and the donor splice site variant of intron 8, c.1398 + 1G > A. Conclusion Molecular diagnosis was achieved in 62 patients with aldosterone synthase deficiency, the largest cohort thus far reported. Six novel genetic variants were identified as possibly pathogenic, extending the spectrum of reported molecular defects of the CYP11B2 gene.

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Iron Deficiency and Obesity – Are we Diagnosing with Appropriate Indicators?

Acta Médica Portuguesa ◽

10.20344/amp.8916 ◽

2018 ◽

Vol 31 (9) ◽

pp. 478 ◽

Cited By ~ 2

Author(s):

Ana Margarida Monteiro ◽

Vera Fernandes ◽

Cláudia Matta-Coelho ◽

Sílvia Paredes ◽

Maria Lopes Pereira ◽

...

Keyword(s):

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Body Mass Index ◽

Iron Deficiency ◽

Body Mass ◽

Obese Patients ◽

Exclusion Criteria ◽

Multidisciplinary Consultation ◽

Deficiency Type

Introduction: We aim to define the iron deficiency prevalence and eventual differences between obese patients with and without metabolic syndrome.Material and Methods: Analysis of patients evaluated at multidisciplinary consultation of obesity in our institution between 2013 and 2015 (n = 260). Iron deficiency: ferritin levels < 15 ng/mL. Exclusion criteria: prior bariatric surgery; lack of ferritin or hemoglobin determinations.Results: We analyzed data from 215 patients (84.2% female) with a mean age of 42.0 ± 10.3 years. The median body mass index was 42.5 (40.0 - 46.8) kg/m2 and 52.1% had metabolic syndrome. Iron deficiency was present in 7.0%, with no differences between genders or between patients with or without metabolic syndrome. Hypertension was associated with lower prevalence of iron deficiency. Type 2 diabetes and hypertension patients had higher levels of ferritin. The multivariate analysis showed that metabolic syndrome and increasing body mass index were predictive of higher risk of iron deficiency while hypertension predicted lower odds of iron deficiency.Discussion: The prevalence of iron deficiency was similar in other published studies. Iron deficiency may be underdiagnosed if based only on ferritin concentrations. In our study, diabetes and hypertension appear to contribute to the increase in ferritin levels described in obesity.Conclusion: Ferritin may not be a reliable index for evaluating iron stores in obese patients, particularly when associated with comorbidities such as type 2 diabetes and hypertension. Further studies are needed to guide the diagnosis and iron supplementation in these patients.

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Molecular genetic verification of isolated mineralocorticoid deficiency due to aldosterone synthase deficiency

Problems of Endocrinology ◽

10.14341/probl200955128-30 ◽

2009 ◽

Vol 55 (1) ◽

pp. 28-30

Author(s):

N Yu Kalinchenko ◽

N A Zubkova ◽

A N Tyulpakov

Keyword(s):

Autosomal Recessive ◽

Molecular Genetic ◽

Autosomal Recessive Disorder ◽

Adrenal Hyperplasia ◽

Genetic Studies ◽

Aldosterone Synthase ◽

Salt Wasting ◽

History Of ◽

17 Hydroxyprogesterone ◽

Aldosterone Synthase Deficiency

Isolated mineralocorticoid deficiency is a rare hereditary autosomal recessive disorder that is characterized by salt wasting and that has the severest manifestations in infants. This paper is the first in the Russian literature to describe cases of isolated aldosterone deficiency. In both cases, the patients were monitored and treated for misdiagnosed congenital adrenal hyperplasia; however, the permanently low level of 17-hydroxyprogesterone could put in doubt the diagnosis and suspect isolated mineralocorticoid deficiency, by keeping in mind a history of salt wasting. By using the presented cases as an example, the authors give an algorithm for the examination and differential diagnosis of this condition and other diseases that have the similar clinical picture. Aldosterone synthase deficiency in patients was verified by molecular genetic studies - there were mutations in the CYP112 gene.

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