Rare Pulmonology News

Disease Profile

Familial hyperaldosteronism type III

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

ageofonset-infancy.svg

ICD-10

E26.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

rnn-autosomaldominant.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

no.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

FH III; Familial hyperaldosteronism type 3; FH-III;

Categories

Congenital and Genetic Diseases; Endocrine Diseases

Summary

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

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 Gprotein-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 genotypephenotype 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-oxoand 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.

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.

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

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.

    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

      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.