Natural History of Apparent Mineralocorticoid Excess Syndrome

Apparent Mineralocorticoid Excess Syndrome Natural History Clinical Protocol

Apparent mineralocorticoid excess (AME) is a rare inherited disease that can cause severe high blood pressure and low blood potassium in children and adults. It is caused by abnormal hormone metabolism and can be fatal. This study will focus on the genetic basis, natural history, disease progression, and survival of people with AME.

Study Overview

• Status: Completed
• Conditions: Apparent Mineralocorticoid Excess Syndrome

Detailed Description

AME is a rare genetic disorder that is caused by a mutated HSD11B2 gene, which encodes the metabolic enzyme 11BHSD2. The altered gene interferes with the ability of 11BHSD2 to inactivate the hormone cortisol. Above-normal cortisol activity then leads to a rise in blood pressure and a reduction of potassium in the blood. It also leads to low levels of the enzyme renin and the hormone aldosterone, both of which are involved in the regulation of long-term blood pressure. Long-term high blood pressure and metabolic defects start at an early age in children with severe AME. In others, AME may start later in life and cause less serious side effects. Symptoms can include poor growth in childhood, delayed puberty, muscle weakness, heart rate irregularity, frequent urination, and thirst. If left untreated, AME can cause serious damage to the eyes, kidneys, heart, and other organs.

Current treatment with the synthetic steroid spironolactone usually improves symptoms; however, despite treatment, some individuals with AME still experience disease progression and even death within years of being diagnosed with AME. Understanding more about AME, how it progresses, and how it affects people differently may help to improve treatment options. The purpose of this study is to examine the genetic basis, natural history, disease progression, and outcome of children and adults with AME. The study will also examine the family members of study participants with AME for any genetic abnormalities and possible mild forms of AME.

This study will last 2 to 7 years. Participants and their family members will attend yearly study visits that will include interviews about medical history, symptoms, and hospital stays; a physical exam; blood pressure testing; and blood and urine collection. Interim reviews of medical records will occur as necessary. Children will undergo an x-ray of the left hand. During the initial study visit, participants will be asked questions about family members and birth size.

• Study Type: Observational
• Enrollment (Actual): 130

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 01060-970
    • University of Sao Paulo
• France
  • Lyon, France, 69322
    • University of Lyon
• United States
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Individuals with apparent mineralocorticoid excess plus their family members

Description

Inclusion Criteria for Participants with AME:

• High blood pressure characterized by low plasma renin and serum aldosterone levels
• Elevated urinary cortisol/cortisone metabolite ratio ([THF + 5aTHF]/THE)
• Molecular genetic diagnosis of AME with two mutations of the HSD11B2 gene

Inclusion Criteria for Family Members without Genetic Diagnosis of AME:

• Carrier of the HSD11B2 mutation that the AME participant has

Exclusion Criteria for All Participants:

• Any other illness or condition that might interfere with study participation

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Rare Diseases Clinical Research Network; Office of Rare Diseases (ORD)
• Investigators: Principal Investigator: Maria I. New, MD, Icahn School of Medicine at Mount Sinai

Publications and helpful links

General Publications

• New MI, Geller DS, Fallo F, Wilson RC. Monogenic low renin hypertension. Trends Endocrinol Metab. 2005 Apr;16(3):92-7. doi: 10.1016/j.tem.2005.02.011.
• Palermo M, Quinkler M, Stewart PM. Apparent mineralocorticoid excess syndrome: an overview. Arq Bras Endocrinol Metabol. 2004 Oct;48(5):687-96. doi: 10.1590/s0004-27302004000500015. Epub 2005 Mar 7.
• Quinkler M, Bappal B, Draper N, Atterbury AJ, Lavery GG, Walker EA, DeSilva V, Taylor NF, Hala S, Rajendra N, Stewart PM. Molecular basis for the apparent mineralocorticoid excess syndrome in the Oman population. Mol Cell Endocrinol. 2004 Mar 31;217(1-2):143-9. doi: 10.1016/j.mce.2003.10.019.

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: May 16, 2007
• First Submitted That Met QC Criteria: May 16, 2007
• First Posted (Estimate): May 17, 2007

Study Record Updates

• Last Update Posted (Estimate): December 11, 2015
• Last Update Submitted That Met QC Criteria: December 10, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Hypertension; Hypokalemia; Metabolic Alkalosis
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Endocrine System Diseases; Disease; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Steroid Metabolism, Inborn Errors; Syndrome; Hyperaldosteronism; Mineralocorticoid Excess Syndrome, Apparent
• Other Study ID Numbers: GCO 04-0474; U54HD064382 (U.S. NIH Grant/Contract); RDCRN 5601 (Other Identifier: Office of Rare Diseases (ORD))