Familial hyperaldosteronism type III

Title

Other Names:

FH III; Familial hyperaldosteronism type 3; FH-III; FH III; Familial hyperaldosteronism type 3; FH-III; FH3 See More

Categories:

Congenital and Genetic Diseases; Endocrine Diseases

This disease is grouped under:

Primary hyperaldosteronism

Summary Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.

Orpha Number: 251274

Definition

Familial hyperaldosteronism type III (FH-III) is a rare heritable form of primary aldosteronism (PA) that is characterized by early-onset severe hypertension, non glucocorticoid-remediable hyperaldosteronism, overproduction of 18-oxocortisol and 18-hydroxycortisol, and profound hypokalemia.

Epidemiology

Seven families with FH-III have been reported to date.

Clinical description

Severe hypertension associated with profound hypokalemia generally manifests during early childhood. It can be accompanied with polydipsia, polyuria, nausea, vomiting and headaches. Marked bilateral adrenal hyperplasia has been described. In exceptional cases, a mild form of FH-III, resembling to FH type II (see this term) has been reported, with normal appearing adrenals and treatable with medical therapy.

Etiology

FH-III is due to heterozygous missense mutations of the KCNJ5 gene (11q24), encoding the G-protein-activated inward rectifier potassium channel GIRK-4. These mutations result in loss of channel selectivity, membrane depolarization of the zona glomerulosa cells of the adrenal cortex, opening of voltage-activated calcium channels, and activation of the calcium signaling pathway that trigger saldosterone biosynthesis. There is a genotype-phenotype correlation, with the mild phenotype observed in patients with the p.G151E and p.Y152C mutations.

Diagnostic methods

Blood and urinary tests show profound hypokalemia, an abnormal aldosterone/renin ratio with increased aldosterone levels not suppressible by dexamethasone, suppressed plasma renin activity, and elevated levels of the hybrid steroids 18-oxo- and 18-hydroxycortisol. Diagnosis is confirmed by genetic testing.

Differential diagnosis

The clinical presentation resembles that of the other familial forms of hyperaldosteronism (FH-I, FH-II) (see these terms).

Genetic counseling

Transmission is autosomal dominant.

Management and treatment

FH-III does not respond to glucocorticoid treatment. Severe cases require bilateral adrenalectomy to normalize blood pressure and hypokalemia, whereas mild cases are treated with medical therapy with aldosterone antagonists and/or other antihypertensive drugs if required.

Prognosis

In severe cases treated with bilateral adrenalectomy, life-long glucocorticoid and mineralocorticoid replacement therapy is required. In mild cases, prognosis is good with medical treatment.

Visit the Orphanet disease page for more resources.

Last updated: 6/1/2014

Symptoms Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 21 |

Medical Terms	Other Names	Learn More: HPO ID
100% of people have these symptoms
Abnormal circulating renin	Abnormal plasma renin	0040084
Hypertension		0000822
80%-99% of people have these symptoms
Adrenal hyperplasia	Enlarged adrenal glands	0008221
Glucocortocoid-insensitive primary hyperaldosteronism		0011740
Hypokalemia	Low blood potassium levels	0002900
5%-29% of people have these symptoms
Epistaxis	Bloody nose Frequent nosebleeds Nose bleed Nose bleeding Nosebleed [ more ]	0000421
Headache	Headaches	0002315
Hypercalciuria	Elevated urine calcium levels	0002150
Intracranial hemorrhage	Bleeding within the skull	0002170
Left ventricular hypertrophy		0001712
Metabolic acidosis		0001942
Metabolic alkalosis		0200114
Muscle weakness	Muscular weakness	0001324
Nausea		0002018
Polydipsia	Extreme thirst	0001959
Polyuria	Increased urine output	0000103
Prolonged QT interval		0001657
Tinnitus	Ringing in ears Ringing in the ears [ more ]	0000360
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance		0000006
Decreased circulating renin level		0003351
Hyperaldosteronism	Elevated plasma aldosterone Increased aldosterone Increased aldosterone production [ more ]	0000859

Showing of 21 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2021

Do you have updated information on this disease? We want to hear from you.

Diagnosis Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from MedlinePlus Genetics.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Primary Aldosteronism Foundation
3533 E Ahwatukee CT
Phoenix, AZ 85044
Telephone: (602) 726-0665
E-mail: info@primaryaldosteronism.org
Website: https://www.primaryaldosteronism.org/

Do you know of an organization? We want to hear from you.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Familial hyperaldosteronism type III . Click on the link to view a sample search on this topic.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

You can help advance
rare disease research! You can help advance rare disease research!