O hiperaldosteronismo familiar (FH) é a forma hereditária de aldosteronismo primário (PA), que compreende três subtipos identificados até o momento: FH tipo I (FH-I) caracterizado por hipertensão de início precoce, hiperaldosteronismo dependente do hormônio adrenocorticotrófico remediável por glicocorticóide (ACTH), hipocalemia variável e superprodução de 18-oxocortisol e 18-hidroxicortisol; HF tipo II (HF-II) caracterizada por hipertensão de gravidade variável e hiperaldosteronismo não suprimível pela dexametasona; e FH tipo III (FH-III) caracterizada por hipocalemia profunda, hipertensão grave de início precoce, hiperaldosteronismo não remediável com glicocorticóides e superprodução de 18-oxocortisol e 18-hidroxicortisol.
Introdução
O que você precisa saber de cara
O hiperaldosteronismo familiar (FH) é a forma hereditária de aldosteronismo primário (PA), que compreende três subtipos identificados até o momento: FH tipo I (FH-I) caracterizado por hipertensão de início precoce, hiperaldosteronismo dependente do hormônio adrenocorticotrófico remediável por glicocorticóide (ACTH), hipocalemia variável e superprodução de 18-oxocortisol e 18-hidroxicortisol; HF tipo II (HF-II) caracterizada por hipertensão de gravidade variável e hiperaldosteronismo não suprimível pela dexametasona; e FH tipo III (FH-III) caracterizada por hipocalemia profunda, hipertensão grave de início precoce, hiperaldosteronismo não remediável com glicocorticóides e superprodução de 18-oxocortisol e 18-hidroxicortisol.
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 18 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 49 características clínicas mais associadas, ordenadas por frequência.
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
6 genes identificados com associação a esta condição.
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkyla
Membrane
Sinoatrial node dysfunction and deafness
A disease characterized by congenital severe to profound deafness without vestibular dysfunction, associated with episodic syncope due to intermittent pronounced bradycardia.
A cytochrome P450 monooxygenase that catalyzes the biosynthesis of aldosterone, the main mineralocorticoid in the human body responsible for salt and water homeostasis, thus involved in blood pressure regulation, arterial hypertension, and the development of heart failure (PubMed:11856349, PubMed:12530636, PubMed:1518866, PubMed:15356073, PubMed:1594605, PubMed:1775135, PubMed:22446688, PubMed:23322723, PubMed:9814482, PubMed:9814506). Catalyzes three sequential oxidative reactions of 11-deoxyco
Mitochondrion inner membrane
Corticosterone methyloxidase 1 deficiency
Autosomal recessive disorder of aldosterone biosynthesis. There are two biochemically different forms of selective aldosterone deficiency be termed corticosterone methyloxidase (CMO) deficiency type 1 and type 2. In CMO-1 deficiency, aldosterone is undetectable in plasma, while its immediate precursor, 18-hydroxycorticosterone, is low or normal.
A cytochrome P450 monooxygenase involved in the biosynthesis of adrenal corticoids (PubMed:12530636, PubMed:1518866, PubMed:1775135, PubMed:18215163, PubMed:23322723). Catalyzes a variety of reactions that are essential for many species, including detoxification, defense, and the formation of endogenous chemicals like steroid hormones. Steroid 11beta, 18- and 19-hydroxylase with preferred regioselectivity at 11beta, then 18, and lastly 19 (By similarity). Catalyzes the hydroxylation of 11-deoxyc
Mitochondrion inner membrane
Adrenal hyperplasia 4
A form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: 'salt wasting' (SW, the most severe type), 'simple virilizing' (SV, less severely affected patients), with normal aldosterone biosynthesis, 'non-classic form' or late-onset (NC or LOAH) and 'cryptic' (asymptomatic).
Voltage-sensitive calcium channel that gives rise to T-type calcium currents. T-type calcium channels belong to the 'low-voltage activated (LVA)' group. A particularity of this type of channel is an opening at quite negative potentials, and a voltage-dependent inactivation (PubMed:27149520, PubMed:9670923, PubMed:9930755). T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle (Probabl
Cell membrane
Epilepsy, idiopathic generalized 6
A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain.
Voltage-gated and osmosensitive chloride channel. Forms a homodimeric channel where each subunit has its own ion conduction pathway. Conducts double-barreled currents controlled by two types of gates, two fast glutamate gates that control each subunit independently and a slow common gate that opens and shuts off both subunits simultaneously. Displays inward rectification currents activated upon membrane hyperpolarization and extracellular hypotonicity (PubMed:16155254, PubMed:17567819, PubMed:19
Cell membraneBasolateral cell membraneCell projection, dendritic spine membraneCell projection, axon
Epilepsy, idiopathic generalized 11
A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain.
Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by external barium. This potassium channel is control
Membrane
Long QT syndrome 13
A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy.
Variantes genéticas (ClinVar)
831 variantes patogênicas registradas no ClinVar.
Vias biológicas (Reactome)
14 vias biológicas associadas aos genes desta condição.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
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Early-onset hypertension associated with a CACNA1H variant of uncertain significance: a case report and literature review.
The prevalence of early-onset hypertension is rising annually and is accompanied by progressive target organ damage, contributing to a higher risk of cardiovascular mortality. In patients with early-onset hypertension characterized by refractory hypertension, elevated plasma aldosterone levels, and a family history of hypertension, monogenic hereditary hypertension, such as familial hyperaldosteronism, should be suspected, although this condition is rare. A 36-year-old male patient with hypertension fails to achieve target blood pressure despite receiving four antihypertensive medications, including a diuretic. The patient exhibited elevated plasma aldosterone levels, while the aldosterone-to-renin ratio and serum potassium levels remain within normal ranges. Further genetic analysis identifies a heterozygous variant of uncertain significance in the CACNA1H gene (nucleotide change: c.3988G > A, amino acid change: p.V1330I, chromosomal location: chr16:1260601). This genetic variant has not been previously reported. The CACNA1H gene is associated with familial hyperaldosteronism type IV. Sanger sequencing validation and family pedigree analysis were performed, confirming an autosomal dominant inheritance pattern among family members. For patients with early-onset hypertension characterized by refractory hypertension, elevated plasma aldosterone levels, and a family history of hypertension, monogenic forms of hypertension, such as familial hyperaldosteronism, should be suspected. However, For patients with negative ARR but atypical clinical manifestations of elevated aldosterone levels, exclusive reliance on common biochemical markers, such as the aldosterone-to-renin ratio and serum potassium levels, may lead to misdiagnosis or underdiagnosis. Therefore, in addition to routine biochemical markers, genetic testing should be considered a complementary diagnostic tool for patients with early-onset hypertension and a family history of hypertension.
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Internal medicine (Tokyo, Japan)Unveiling the Causal Relationship of Cardiovascular Burden in Primary Aldosteronism by Genome-Wide Association and Mendelian Randomization: A Possible Solution?
Journal of the American Heart AssociationPrimary Aldosteronism and Risk of Cardiovascular Outcomes: Genome-Wide Association and Mendelian Randomization Study.
Journal of the American Heart AssociationGenetic Testing for Primary Aldosteronism in SPAIN: Results From the SPAIN-ALDO Registry and Review of the Literature.
The Journal of clinical endocrinology and metabolismCase report: Two novel compound heterozygous variant of SLC12A3 gene in a gitelman syndrome family and literature review.
Frontiers in geneticsImpact of primary aldosteronism on kidney function: results from the SPAIN-ALDO registry.
Journal of hypertensionX-linked transient antenatal Bartter syndrome related to MAGED2 gene: Enriching the phenotypic description and pathophysiologic investigation.
Genetics in medicine : official journal of the American College of Medical GeneticsRare correlation of somatic PRKACA mutations with pregnancy-associated aldosterone- and cortisol-producing adenomas: a case report and literature review.
BMC endocrine disordersParadoxes in magnesium transport in type 1 Bartter's syndrome and Gitelman's syndrome: a modeling analysis.
American journal of physiology. Renal physiology[Two Cases of Pseudo-Bartter Syndrome in Childhood: When to Suspect a Rare Onset Pattern of Cystic Fibrosis].
Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologiaMacrophages preserve endothelial cell specialization in the adrenal gland to modulate aldosterone secretion and blood pressure.
Cell reportsPostnatal renal tubule development: roles of tubular flow and flux.
Current opinion in nephrology and hypertensionDouble CYP11B1/CYP11B2 Immunohistochemistry and Detection of KCNJ5 Mutations in Primary Aldosteronism.
The Journal of clinical endocrinology and metabolismBartter Syndrome Presenting as Arginine-Vasopressin Resistance: A Report of 2 Cases.
The American journal of case reportsMonogenic Hypertension Linked to the Renin-Angiotensin-Aldosterone System.
Anatolian journal of cardiologyReport on three cases of familial primary aldosteronism type IV.
Journal of hypertension[Cystic fibrosis primarily presenting with pseudo-Bartter syndrome: a report of three cases and literature review].
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatricsProtein Quality Control of NKCC2 in Bartter Syndrome and Blood Pressure Regulation.
CellsKCNJ5 mutations in familial and non-familial primary aldosteronism.
European journal of endocrinologyThe influence of cortisol co-secretion on clinical characteristics and postoperative outcomes in unilateral primary aldosteronism.
Frontiers in endocrinologyPolymyxin B-induced Bartter syndrome.
BMJ case reportsThe association between blood pressure variability and renal damage in patients with primary aldosteronism.
Journal of clinical hypertension (Greenwich, Conn.)Cardiovascular Outcomes of KCNJ5 Mutated Aldosterone-Producing Adenoma: A Systematic Review.
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical EndocrinologistsReview of childhood genetic nephrolithiasis and nephrocalcinosis.
Frontiers in genetics17α-hydroxylase/17,20-lyase Deficiency Diagnosed at 45 Years of Age with Hyperaldosteronism.
Internal medicine (Tokyo, Japan)Zona Glomerulosa-Derived Klotho Modulates Aldosterone Synthase Expression in Young Female Mice.
EndocrinologyFamilial hyperaldosteronism: an European Reference Network on Rare Endocrine Conditions clinical practice guideline.
European journal of endocrinologyAdult classic Bartter syndrome: a case report with 5-year follow-up and literature review.
Endocrine journalPractical consensus for the treatment and follow-up of primary aldosteronism: a multidisciplinary consensus document.
EndocrineDouble somatic mutations in CTNNB1 and GNA11 in an aldosterone-producing adenoma.
Frontiers in endocrinologyDifferences in the clinical and hormonal presentation of patients with familial and sporadic primary aldosteronism.
Frontiers in endocrinologyAUP1 Regulates the Endoplasmic Reticulum-Associated Degradation and Polyubiquitination of NKCC2.
CellsScreening and diagnosis of primary aldosteronism. Consensus document of all the Spanish Societies involved in the management of primary aldosteronism.
EndocrineMicroRNAs in aldosterone production and action.
Vitamins and hormonesBartter syndrome-like phenotype in a patient with type 2 diabetes mellitus.
BMJ case reportsChronic activation of adrenal Gq signaling induces Cyp11b2 expression in the zona fasciculata and hyperaldosteronism.
Molecular and cellular endocrinologyUnilateral Primary Aldosteronism: Long-Term Disease Recurrence After Adrenalectomy.
Hypertension (Dallas, Tex. : 1979)A case of pseudo-Bartter/Gitelman syndrome caused by long-term laxative abuse, leading to end-stage kidney disease.
CEN case reportsPseudo-Bartter syndrome as the initial presentation of cystic fibrosis in children: an important diagnosis not to be missed.
BMJ case reportsIdentification of a novel intronic mutation of MAGED2 gene in a Chinese family with antenatal Bartter syndrome.
BMC medical genomicsRenin as a Biomarker to Guide Medical Treatment in Primary Aldosteronism Patients. Findings from the SPAIN-ALDO Registry.
High blood pressure & cardiovascular prevention : the official journal of the Italian Society of HypertensionNo extra-adrenal aldosterone production in various human cell lines.
Journal of molecular endocrinologyMultifocal, Asymmetric Bilateral Primary Aldosteronism Cannot be Excluded by Strong Adrenal Vein Sampling Lateralization: An International Retrospective Cohort Study.
Hypertension (Dallas, Tex. : 1979)Successful antenatal treatment of MAGED2-related Bartter syndrome and review of treatment options and efficacy.
Prenatal diagnosisClinical analysis of salt-wasting in infants due to genetic aetiology.
Endokrynologia PolskaEpigenetic alterations of 11beta-hydroxysteroid dehydrogenase 1 gene in the adipose tissue of patients with primary aldosteronism.
Endocrine journalCross-Disciplinary Approach of Adrenal Tumors: Insights into Primary Aldosteronism-Related Mineral Metabolism Status and Osteoporotic Fracture Risk.
International journal of molecular sciencesPrimary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study.
Cardiovascular diabetologyWater and Electrolyte Content in Salt-Dependent HYpertension in the SKIn (WHYSKI): Effect of Surgical Cure of Primary Aldosteronism.
High blood pressure & cardiovascular prevention : the official journal of the Italian Society of HypertensionBartter Syndrome Unveiled: Unraveling the Masquerade of Neuroregression.
Indian journal of pediatricsUrine steroid metabolomics as a diagnostic tool in primary aldosteronism.
The Journal of steroid biochemistry and molecular biologyThe predictors of long-term outcomes after targeted therapy for primary Aldosteronism.
Journal of the Formosan Medical Association = Taiwan yi zhiSingle-Nucleus Analysis Reveals Tumor Heterogeneity of Aldosterone-Producing Adenoma.
Hypertension (Dallas, Tex. : 1979)Long-Term Indomethacin Treatment in a Chinese Child with Gitelman Syndrome: Case Report and Literature Review on its Efficacy and Tolerance.
The American journal of case reportsExpanding Genotype-Phenotype Correlation of CLCNKA and CLCNKB Variants Linked to Hearing Loss.
International journal of molecular sciencesRecurrent transient severe hypocalcaemia in two siblings with type 1 Bartter syndrome.
Nephrology (Carlton, Vic.)[Mechanism of miR-186-5p Regulating PRKAA2 to Promote Ferroptosis in Lung Adenocarcinoma Cells].
Zhongguo fei ai za zhi = Chinese journal of lung cancerLiddle syndrome presenting with normal aldosterone levels: A case report.
MedicineIs adrenal venous sampling always necessary to differentiate between unilateral and bilateral primary aldosteronism? Lesson from the SPAIN-ALDO register.
EndocrineRewriting DNA in the body lowers cholesterol.
Science (New York, N.Y.)Genome mining yields putative disease-associated ROMK variants with distinct defects.
PLoS geneticsTherapeutic management of congenital forms of endocrine hypertension.
European journal of endocrinologyCACNA1D Gene Polymorphisms Associate With Increased Blood Pressure and Salt Sensitivity of Blood Pressure in White Individuals.
Hypertension (Dallas, Tex. : 1979)Uncommon Presentation of Cystic Fibrosis: A Case Report and Literature Review.
CureusClinical Research on Rett Syndrome: Central Hypoxemia and Hypokalemic Metabolic Alkalosis.
Alternative therapies in health and medicinePathology and gene mutations of aldosterone-producing lesions.
Endocrine journalBartter Syndrome: A Systematic Review of Case Reports and Case Series.
Medicina (Kaunas, Lithuania)Somatic SLC30A1 mutations altering zinc transporter ZnT1 cause aldosterone-producing adenomas and primary aldosteronism.
Nature geneticsMechanism of DYRK1a in myocardial ischemia-reperfusion injury by regulating ferroptosis of cardiomyocytes.
The Kaohsiung journal of medical sciencesIsradipine therapy in Cacna1dIle772Met/+ mice ameliorates primary aldosteronism and neurologic abnormalities.
JCI insightEmerging association between KCNJ5 mutations and vascular failure in primary aldosteronism.
Hypertension research : official journal of the Japanese Society of HypertensionPattern of hereditary renal tubular disorders in Egyptian children.
The Turkish journal of pediatricsATP1A1-linked diseases require a malfunctioning protein product from one allele.
Biochimica et biophysica acta. Molecular cell researchLong-read sequencing identifies a common transposition haplotype predisposing for CLCNKB deletions.
Genome medicinePrimary aldosteronism: molecular medicine meets public health.
Nature reviews. NephrologyA novel homozygous CLCNKB variant: An early presentation of classic Bartter syndrome in a neonate.
Birth defects researchGenotypic variability in patients with clinical diagnosis of Bartter syndrome type 3.
Scientific reportsClinical Findings and Genetic Analysis of Nine Mexican Families with Bartter Syndrome.
Archives of medical researchAdrenal Anion Channels: New Roles in Zona Glomerulosa Physiology and in the Pathophysiology of Primary Aldosteronism.
Handbook of experimental pharmacologyKCNJ5 mutation is a predictor for recovery of endothelial function after adrenalectomy in patients with aldosterone-producing adenoma.
Hypertension research : official journal of the Japanese Society of HypertensionDecaying kidney function during cirrhosis correlates with remodeling of distal colon aldosterone target gene expression.
American journal of physiology. Gastrointestinal and liver physiologyRelevance of KCNJ5 in Pathologies of Heart Disease.
International journal of molecular sciencesEffect of Obesity on Clinical Characteristics of Primary Aldosteronism Patients at Diagnosis and Postsurgical Response.
The Journal of clinical endocrinology and metabolismCaV3.2 (CACNA1H) in Primary Aldosteronism.
Handbook of experimental pharmacologySomatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production.
Nature geneticsA Novel Enzymatic Hydrolysis Method for Urine Aldosterone Quantification: A Case for Reassessing Clinical Cut-Offs of Primary Aldosteronism.
Clinical chemistryGitelman Syndrome: A Case Report.
CureusRenin-independent aldosteronism and chronic kidney disease in diabetes: Observational and Mendelian randomization analyses.
Metabolism: clinical and experimentalAssociações
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Referências e fontes
Bases de dados externas citadas neste artigo
Publicações científicas
Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.
- Germline and somatic genetic drivers of adrenocortical tumours.Best practice & research. Clinical endocrinology & metabolism· 2026· PMID 41876309mais citado
- Primary Hyperaldosteronism: Epidemiology, Diagnosis, and Clinical Associations.
- Description of the novel variant c.784delG;p. (Ala262Profs*68) at BSND gene and its association with Bartter Syndrome Type Iva.
- Clinical implications of aldosterone responsiveness to adrenocorticotropic hormone stimulation in two major subtypes of primary aldosteronism.
- Early-onset hypertension associated with a CACNA1H variant of uncertain significance: a case report and literature review.
- One-stop evaluation using [(68)Ga]Ga-Pentixafor PET integrated with contrast-enhanced CT for visualization and localization of adrenal nodules in patients with primary aldosteronism.
- New mutation of CACNA1H p.Tyr613Phe in hyperaldosteronism: a case report.
- Primary Aldosteronism: Small Molecule Antagonists of Mutant KCNJ5 Potassium Channels.
- Familial Hyperaldosteronism Type IV in a Mother-Daughter Pair.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:371861(Orphanet)
- MONDO:0016525(MONDO)
- GARD:20630(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Q25339349(Wikidata)
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar
