Dataset Information

A Novel Mutation of the CYP11B2 in a Saudi Infant with Primary Hypoaldosteronism.

ABSTRACT: Isolated hypoaldosteronism is a rare autosomal recessive disease presenting with severe salt wasting and failure to thrive in infancy. A 6-month-old Saudi girl born to consanguineous parents was referred from primary health care for failure to thrive and developmental delay. Laboratory tests revealed hyponatremia, hyperkalemia, and metabolic acidosis with high renin and low aldosterone. Blood samples were collected for endocrine and genetic studies. Sequence analysis of the CYP11B2 revealed a T to A transition at position 1398 + 2 in exon 8 of the gene in a homozygous state (c.1398+T>A). This result was confirmed by sequencing an independent PCR product. Given the position of the transition at a highly conserved nucleotide and the predictions of different bioinformatic algorithms, it is likely that the mutation is the pathogenic cause of this condition. This result was compared with the reference NM_000498.3. Here, we report a novel homozygous mutation resulting in aldosterone synthase deficiency. To the best of our knowledge, this mutation has not been described in the literature or in any database thus far. The mutation manifested as a rare inherited disease in an infant exhibiting critical salt loss. An adequate replacement treatment will give a good long-term prognosis.

SUBMITTER: Alfaraidi L

PROVIDER: S-EPMC5672603 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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A Novel Mutation of the <i>CYP11B2</i> in a Saudi Infant with Primary Hypoaldosteronism.

Alfaraidi Lama L Alfaifi Abrar A Alquaiz Rawan R Almijmaj Faten F Mawlawi Horia H

Case reports in endocrinology 20171023

Isolated hypoaldosteronism is a rare autosomal recessive disease presenting with severe salt wasting and failure to thrive in infancy. A 6-month-old Saudi girl born to consanguineous parents was referred from primary health care for failure to thrive and developmental delay. Laboratory tests revealed hyponatremia, hyperkalemia, and metabolic acidosis with high renin and low aldosterone. Blood samples were collected for endocrine and genetic studies. Sequence analysis of the <i>CYP11B2</i> reveal ...[more]

PMID: 29201470

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Project description: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.

Dataset Information

A Novel Mutation of the CYP11B2 in a Saudi Infant with Primary Hypoaldosteronism.

Publications

A Novel Mutation of the <i>CYP11B2</i> in a Saudi Infant with Primary Hypoaldosteronism.

Similar Datasets

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