Two novel mutations of the CYP11B2 gene in a Japanese patient with aldosterone deficiency type 1

Kondo, Eisuke; Nakamura, Akie; Homma, Keiko; Hasegawa, Tomonobu; Yamaguchi, Takeshi; Narugami, Masahiko; Hattori, Tetsuo; Aoyagi, Hayato; Ishizu, Katsura; Tajima, Toshihiro

doi:10.1507/endocrj.ej12-0248

Cited by 11 publications

(15 citation statements)

References 14 publications

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“…Cases of aldosterone synthase deficiency have been reported in various ethnic groups, including Europeans, North Americans, and Asians (9,10,11,12). One previous case of aldosterone synthase deficiency in a patient of Turkish origin was reported from Japan (4).…”

Section: Discussionmentioning

confidence: 99%

Corticosterone Methyl Oxidase Deficiency Type 1 with Normokalemia in an Infant

Üstyol¹,

Atabek²,

Taylor³

et al. 2016

Jcrpe

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Isolated aldosterone synthase deficiency may result in life-threatening salt-wasting and failure to thrive. The condition involves hyperkalemia accompanying hyponatremia. Two types of aldosterone synthase deficiency may be observed depending on hormone levels: corticosterone methyl oxidase type 1 (CMO 1) and CMO 2. Herein, we describe a Turkish infant patient with aldosterone synthase deficiency who presented with failure to thrive and salt wasting but with normal potassium levels. Urinary steroid characteristics were compatible with CMO I deficiency. Diagnosis of aldosterone synthase deficiency was confirmed by mutational analysis of the CYP11B2 gene which identified the patient as homozygous for two mutations: c.788T>A (p.Ile263Asn) and c.1157T>C (p.Val386Ala). Family genetic study revealed that the mother was heterozygous for c.788T>A and homozygous for c.1157T>C and the father was heterozygous for both c.788T>A and c.1157T>C. To the best of our knowledge, this is only the second Turkish case with a confirmed molecular basis of type 1 aldosterone synthase deficiency. This case is also significant in showing that spot urinary steroid analysis can assist with the diagnosis and that hyperkalemia is not necessarily part of the disease.

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Section: Discussionmentioning

confidence: 99%

Corticosterone Methyl Oxidase Deficiency Type 1 with Normokalemia in an Infant

Üstyol¹,

Atabek²,

Taylor³

et al. 2016

Jcrpe

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show abstract

“…Typically, the disease manifests in the first weeks of life with nausea, vomiting, feeding problems and failure to thrive in the neonatal period. Isolated aldosterone deficiency is associated with neonatal salt-wasting syndrome resulting in hyponatremia, hyperkalaemia, metabolic acidosis and marked elevated renin with low or unappropriated normal aldosterone levels (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Usually, clinical severity improves with age and patients are frequently asymptomatic during adulthood despite not having mineralocorticoid therapy (16).…”

Section: Introductionmentioning

confidence: 99%

“…Most of the cases reported in the literature are from Iranian Jewish patients (5,16,17), but cases from Turkey (14,18) , Japan (7,8) and Israel (9,19) have also been described. To our knowledge, there has been no previous report of Portuguese cases of AS deficiency, especially with confirmed genetic analysis.…”

Section: Introductionmentioning

confidence: 99%

Congenital hyperreninemic hypoaldosteronism due to aldosterone synthase deficiency type I in a Portuguese patient – Case report and review of literature

Lages¹,

Vale²,

Oliveira³

et al. 2019

Archives of Endocrinology and Metabolism

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Hyperreninemic hypoaldosteronism due to aldosterone synthase (AS) deficiency is a rare condition typically presenting as salt-wasting syndrome in the neonatal period. A one-month-old Portuguese boy born to non-consanguineous parents was examined for feeding difficulties and poor weight gain. A laboratory workup revealed severe hyponatremia, hyperkaliaemia and high plasma renin with unappropriated normal plasma aldosterone levels, raising the suspicion of AS deficiency. Genetic analysis showed double homozygous of two different mutations in the CYP11B2 gene: p.Glu198Asp in exon 3 and p.Val386Ala in exon 7. The patient maintains regular follow-up visits in endocrinology clinics and has demonstrated a favourable clinical and laboratory response to mineralocorticoid therapy. To our knowledge, this is the first Portuguese case of AS deficiency reported with confirmed genetic analysis.

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“…Compound heterozygosity has been reported when phenotypically unaffected parents contribute to each allele with a heterozygous mutation, rendering phenotypes of ASD type 1 in the affected offspring [6,10]. Our current case inherited one of the heterozygous mutations c.977C > A (p.Thr326Lys) maternally, and the other c.523_525delAAG (p.Lys175del) paternally.…”

Section: Discussionmentioning

confidence: 71%

“…Cases of aldosterone synthase deficiency (ASD) have been identified in Iranian Jews, Europeans and North Americans [4]. In Asians, it has been reported in Thai, Japanese and Indian individuals [5,6]. To our knowledge, there has been no report of Chinese cases with confirmed genetic analysis.…”

Section: Introductionmentioning

confidence: 99%

The clinical significance of aldosterone synthase deficiency: report of a novel mutation in the CYP11B2 gene

et al. 2014

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BackgroundAldosterone synthase (CYP11B2) deficiency is a rare autosomal recessive disorder, usually presenting with severe salt-wasting in infancy or stress-induced hyperkalaemia and postural hypotension in adulthood. Neonatal screening for congenital adrenal hyperplasia, another cause of salt wasting, using 17-hydroxyprogesterone measurement would fail to detect aldosterone synthase deficiency, a diagnosis which may be missed until the patient presents with salt-wasting crisis. Due to this potential life-threatening risk, comprehensive hormonal investigation followed by genetic confirmation for suspected patients would facilitate clinical management of the patient and assessment of the genetic implication in their offspring.Case presentationWe describe a 33-year old Chinese man who presented in infancy with life-threatening hyponatraemia and failure to thrive, but remained asymptomatic on fludrocortisone since. Chromosomal analysis confirmed a normal male karyotype of 46, XY. Plasma steroid profile showed high plasma renin activity, low aldosterone level, and elevated 18-hydroxycorticosterone, compatible with type 2 aldosterone synthase deficiency. The patient was heterozygous for a novel CYP11B2 mutation: c.977C > A (p.Thr326Lys) in exon 3. He also carried a heterozygous mutation c.523_525delAAG (p.Lys175del) in exon 6, a known pathogenic mutation causing aldosterone synthase deficiency. Sequencing of CYP11B2 in his parents demonstrated that the mother was heterozygous for c.977C > A, and the father was heterozygous for c.523_525delAAG.ConclusionAlthough a rare cause of hyperreninaemic hypoaldosteronism, aldosterone synthase deficiency should be suspected and the diagnosis sought in patients who present with life-threatening salt-wasting in infancy, as it has a good long-term prognosis when adequate fludrocortisone replacement is instituted. To our knowledge, this is the first Chinese patient in which the molecular basis of aldosterone synthase deficiency has been identified.

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Two novel mutations of the CYP11B2 gene in a Japanese patient with aldosterone deficiency type 1

Cited by 11 publications

References 14 publications

Corticosterone Methyl Oxidase Deficiency Type 1 with Normokalemia in an Infant

Corticosterone Methyl Oxidase Deficiency Type 1 with Normokalemia in an Infant

Congenital hyperreninemic hypoaldosteronism due to aldosterone synthase deficiency type I in a Portuguese patient – Case report and review of literature

The clinical significance of aldosterone synthase deficiency: report of a novel mutation in the CYP11B2 gene

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