Apparent mineralocorticoid excess

Wilson, Robert; Nimkarn, Saroj; New, Maria I.

doi:10.1016/s1043-2760(00)00356-8

Cited by 61 publications

(38 citation statements)

References 75 publications

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“…In general there are few cases of AME reported worldwide, since this is a very rare autosomal recessive disorder (25,27). The boy described in the present paper was clinically diagnosed with AME and molecular fi ndings confi rmed the phenotype.…”

Section: Discussionsupporting

confidence: 64%

“…To date, over 30 different mutations on HSD11B2 gene have been reported worldwide and in many ethnic groups, including Caucasians, Africans, Asians, and American Indians (25)(26)(27)(28). Consanguinity, endogamy or a founder effect for AME have been considered in several families, especially those from ethnics in whom recurrence of certain HSD11B2 mutations is observed (25).…”

Section: Discussionmentioning

confidence: 99%

“…Consanguinity, endogamy or a founder effect for AME have been considered in several families, especially those from ethnics in whom recurrence of certain HSD11B2 mutations is observed (25). The Brazilian family described here is formed by a consanguineous marriage and both father and mother …”

Section: Discussionmentioning

confidence: 99%

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Apparent mineralocorticoid excess syndrome in a Brazilian boy caused by the homozygous missense mutation p.R186C in the HSD11B2 gene

Coeli

Ferraz

Lemos-Marini

et al. 2008

Arq Bras Endocrinol Metab

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The apparent mineralocorticoid excess syndrome (AME) is a rare autosomal recessive disorder due to the defi ciency of 11β-hydroxysteroid dehydrogenase type 2 enzyme (11beta-HSD2). The 11beta-HSD2 enzyme, encoded by HSD11B2 gene, metabolizes active cortisol in cortisone. Mutations on HSD11B2 gene affect the enzyme activity by leading to an excess of cortisol, which causes its inappropriate access to mineralocorticoid receptor. Therefore, cortisol will bind mineralocorticoid receptor. The human HSD11B2 gene maps to chromosome 16q22 and consists of fi ve exons encoding a protein of 405 amino acids. We present here clinical and molecular studies on a Brazilian boy who was born pre-term after an oligodramnious pregnancy. He was diagnosed as having AME at the age of 26 months. His parents are second cousins. Molecular characterization of the HSD11B2 gene revealed the homozygous mutation p.R186C. The patient described here is the second case of HDS11B2 gene mutation reported in Brazilian patients with AME. RESUMO Síndrome de Excesso Aparente de Mineralocorticóide em um Menino Brasileiro Causada pela Mutação p.R186C em Homozigose no Gene HSD11B2.A síndrome de excesso aparente de mineralocorticóide (AME) é uma doença autossômica recessiva rara devido à defi ciência da enzima 11β-hidroxiesteróide desidrogenase tipo 2 (11beta-HSD2). A enzima 11beta-HSD2 metaboliza o cortisol ativo a cortisona. As mutações no gene HSD11B2, que codifi ca a enzima, afetam sua atividade levando a um excesso de cortisol, que terá acesso inapropriado ao receptor de mineralocorticóide, competindo com a ligação da aldosterona. O gene HDS11B2 humano está localizado no cromossomo 16q22 e é formado por 5 éxons que codifi cam uma proteína de 405 aminoáci-dos. Este relato apresenta os estudos clínicos e moleculares de um paciente brasileiro do sexo masculino que nasceu prematuro depois de uma gestação sob oligodrâmnio. Recebeu o diagnóstico de AME com 26 meses de idade.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

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Apparent mineralocorticoid excess syndrome in a Brazilian boy caused by the homozygous missense mutation p.R186C in the HSD11B2 gene

Coeli

Ferraz

Lemos-Marini

et al. 2008

Arq Bras Endocrinol Metab

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“…Most type I AME patients are homozygous for HSD11B2 mutations causing full, or partial loss of activity. It is most commonly found in consanguineous families (3,28,30,31).…”

Section: Cortisol Metabolismmentioning

confidence: 99%

“…It can be classified on the basis of whether it is congenital or acquired, but the two forms share the same pathophysiology: AME is the outcome of defective 11 -hydroxysteroid dehydrogenase type 2 (11 -HSD2) (2,3). This enzyme is predominantly expressed, together with the mineralocorticoid receptor (MR), in the renal distal tubules and collecting ducts (4), in the distal colon, in the salivary glands and also in the placenta where it protects the fetus from an excessive amount of maternal cortisol (F) (5,6) (figure 1).…”

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confidence: 99%

Apparent mineralocorticoid excess syndrome: an overview

Palermo

Quinkler

Stewart

2004

Arq Bras Endocrinol Metab

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Apparent mineralocorticoid excess (AME) syndrome results from defective 11 -hydroxysteroid dehydrogenase type 2 (11 -HSD2). This enzyme is co-expressed with the mineralocorticoid receptor (MR) in the kidney and converts cortisol (F) to its inactive metabolite cortisone (E). Its deficiency allows the unmetabolized cortisol to bind to the MR inducing sodium retention, hypokalemia, suppression of PRA and hypertension. Mutations in the gene encoding 11 -HSD2 account for the inherited form, but a similar clinical picture to AME occurs following the ingestion of bioflavonoids, licorice and carbenoxolone, which are competitive inhibitors of 11 -HSD2. Reduced 11 -HSD2 activity may explain the increased sodium retention in preeclampsia, renal disease and liver cirrhosis. Relative deficiency of 11 -HSD2 activity can occur in Cushing's syndrome due to saturation of the enzyme and explains the mineralocorticoid excess state that characterizes ectopic ACTH syndrome. Reduced placental 11 -HSD2 expression might explain the link between reduced birth weight and adult hypertension. Polymorphic variability in the HSD11B2 gene in part determines salt sensitivity, a forerunner for adult hypertension onset. AME represents a spectrum of mineralocorticoid hypertension with severity reflecting the underlying genetic defect in the 11 -HSD2; although AME is a genetic disorder, several exogenous compounds can bring about the symptoms by inhibiting 11 -HSD2 enzyme. Substrate excess as seen in Cushing's syndrome and ACTH ectopic production can overwhelm the capacity of 11 -HSD2 to convert F to E, leading up to an acquired form of AME. A síndrome do excesso aparente de mineralocorticóides (SEAM) resulta de defeito na 11 -hidroxisteróide desidrogenase tipo 2 (11 -HSD2). Esta enzima é co-expressa com o receptor mineralocorticóide (RM) nos rins e converte cortisol (F) em cortisona (E), seu metabólito inativo. Deficiência desta enzima permite que o cortisol não metabolizado se ligue ao RM, induzindo retenção de sódio, hipocalemia, supressão da APR e hipertensão. Mutações no gene que codifica a 11 -HSD2 são responsáveis pela forma herdada, mas um quadro clínico semelhante de SEAM ocorre durante ingestão dos bioflavonóides, alcaçuz e carbenoxolona, que são inibidores competitivos da 11 -HSD2. Redução na atividade da 11 -HSD2 pode explicar o aumento da retenção de sódio na pré-eclâmpsia, na doença renal e na cirrose hepática. Deficiência relativa de atividade da 11 -HSD2 pode ocorrer na síndrome de Cushing devido à saturação da enzima e explicar o estado de excesso mineralocorticóide que caracteriza a síndrome do ACTH ectópico. Redução da expressão placentária da 11 -HSD2 poderia justificar a ligação entre baixo peso ao nascer e hipertensão no adulto. Variabili-

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Endocrinology, Molecular

Bolander

2006

Encyclopedia of Molecular Cell Biology and Molecular Medicine

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Apparent mineralocorticoid excess

Cited by 61 publications

References 75 publications

Apparent mineralocorticoid excess syndrome in a Brazilian boy caused by the homozygous missense mutation p.R186C in the HSD11B2 gene

Apparent mineralocorticoid excess syndrome in a Brazilian boy caused by the homozygous missense mutation p.R186C in the HSD11B2 gene

Apparent mineralocorticoid excess syndrome: an overview

Endocrinology, Molecular

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