Novel missense mutation of mineralocorticoid receptor gene. Researched pathways related to pseudohypoaldosteronism, type 1 include transport, excretion, pathogenesis, water homeostasis, localization. Diagnosis and management of pseudohypoaldosteronism type 1 in. Evidence for genetic heterogeneity of pseudohypoaldosteronism. Genetic testing for pseudohypoaldosteronism, other and. Mutations in subunits of the epithelial sodium channel.
Clinical and molecular features of type 1 pseudohypoaldosteronism. Nelson,3 edith hummler,4 and birgitte monster christensen1. Mutations in subunits of the epithelial sodium channel cause. In 4 familial cases of autosomal dominant type i pseudohypoaldosteronism and in 1 sporadic patient, geller et al. Mechanisms of type i and type ii pseudohypoaldosteronism.
Pseudohypoaldosteronism type i phai is sometimes dominantly inherited and is characterized by mutations causing a nearabsence of mineralocorticoid receptors in the kidneys. Analysis of both chromosome regions together yielded a lod score of 8. Voltagedependent gating underlies loss of enac function in pseudohypoaldosteronism type 1 volodymyr kucher, nina boiko, oleh pochynyuk, and james d. The molecular defect involved in the systemic autosomal recessive form of the. The journal publishes original papers and commentaries which.
Mar 28, 20 we report a newborn girl with lifethreatening hyperkalemia and salt wasting crisis due to severe autosomal recessive multiple target organ dysfunction pseudohypoaldosteronism type 1 mtod pha1. Pseudohypoaldosteronism type 1 pha1 is a rare condition. Pseudohypoaldostenism in newborns is known to result transiently from urinary tract infection, renal dysplasia or obstructive reflux nephropathy and should be ruled out as in our case 4. The autosomal dominant form is milder than autosomal recessive.
Phenotypic diversity and correlation with the genotypes of. There is resultant salt wasting in the neonatal period, with hyperkalaemia and metabolic acidosis. Dec 02, 2011 autosomal recessive pseudohypoaldosteronism type 1 is a disorder of electrolyte metabolism characterized by excess loss of salt in the urine and high concentrations of sodium in sweat, stool, and saliva. The autosomal dominant form tends to be associated with milder symptoms. Pseudohypoaldosteronism type 2 genetics home reference. Novel missense mutation of mineralocorticoid receptor gene in.
Only after results confirm isolated resistance to aldosterone can the diagnosis of type 1 pha be confidently made. Typically, these children have elevated aldosterone levels due to end organ resistance to aldosterone. Thus far, pha1 has been attributed to mutations affecting the mineralocorticoid receptor or any of the three subunits assembling the amiloridesensitive epithelial sodium channel enac. Pseudohypoaldosteronism type 1 pha1 is a rare condition characterized by neonatal salt loss with dehydration, hypotension, hyperkalemia, and metabolic acidosis, despite elevated plasma aldosterone levels and pra. Pseudohypoaldosteronism type 1 pha1 is a monogenic disease caused by mutations in the genes encoding the human mineralocorticoid receptor mr or the. Five novel mutations in the scnn1a gene causing autosomal.
Treatment is with a highsodium diet and sometimes fludrocortisone. Autosomalrecessive pha1 that involves a genetic defect in the epithelial sodium channel that affects all aldosterone target organs including the kidney, colon and sweat glands. Pseudohypoaldosteronism type 2 pha2, sometimes referred to as gordon hyperkalemiahypertension syndrome patients have hypertension and hyperkalemia despite having normal glomerular filtration rate. Primary pseudohypoaldosteronism type 1 pha1 is a heterogeneous syndrome characterised by saltwasting due to unresponsiveness of target organ to mineralocorticoids. The study of pseudohypoaldosteronism, type 1 has been mentioned in research publications which can be found using our bioinformatics tool below. Mar 15, 2017 geller ds, zhang j, zennaro mc, et al. Pseudohypoaldosteronism pha types i and ii are curious genetic disorders that. However, sodium can also be removed from the body through other tissues, such as the sweat glands and colon. Voltagedependent gating underlies loss of enac function. Hypoaldosteronism is an endocrine disease characterized by hyperkalemia and mild hyperchloremic metabolic acidosis with normal anion gap type 4 renal. Primary pseudohypoaldosteronism type 1 pha 1 is a heterogeneous syndrome characterised by saltwasting due to unresponsiveness of target organ to mineralocorticoids. Mechanisms of type i and type ii pseudohypoaldosteronism jasn.
Pha2 is clinically characterised by hypertension, hyperkalaemia, metabolic acidosis and normal renal function. Pseudohypoaldosteronism type 1 pha1 is a rare autosomal recessive disease characterized by impaired transepithelial sodium transport. Affected children develop lifethreatening salt loss of neonatal onset, hyperkalemia, and acidosis. Symptoms may result from hypotension, hypovolemia, hyponatremia, and hyperkalemia. At least two forms of pha1 have been defined since then 27. In affected members of a japanese family with pha1a, tajima et al. Jul 31, 20 pseudohypoaldosteronism type ii pha ii, also referred to as gordon syndrome, is a rare renal tubular disease that is inherited in an autosomal manner. Pha1 is a rare condition that has been estimated to affect 1 in 80,000 newborns. Pseudohypoaldosteronism type i genitourinary disorders. Pseudohypoaldosteronism type 2 pha2 is caused by problems that affect regulation of the amount of sodium and potassium in the body. We report a newborn girl with lifethreatening hyperkalemia and salt wasting crisis due to severe autosomal recessive multiple target organ dysfunction pseudohypoaldosteronism type 1 mtod pha1. Omim entry % 145260 pseudohypoaldosteronism, type iia. Pseudohypoaldosteronism type 1 pha1 is a rare hereditary saltwasting disorder first described by cheek and perry in 1958.
There is an autosomal recessive form, and an autosomal dominant or sporadic form. Elucidating the underlying molecular pathogenesis of nr3c2 mutants causing autosomal dominant pseudohypoaldosteronism type 1. Autosomal recessive pseudohypoaldosteronism type 1 genetic. However, the condition is due to a failure of response to aldosterone, and levels of aldosterone are actually elevated, due to a lack of feedback inhibition. Pseudohypoaldosteronism an overview sciencedirect topics. Pseudohypoaldosteronism type 1 phai is a rare lifethreat ening disease that presents in the first few days of life with salt wasting, hyperkalemia, and acidosis. Familial pseudohypoaldosteronism type 1 pha1 occurs in two genetically and clinically distinguishable variants. Pseudohypoaldosteronism type 1 pha1 is further differentiated into, i hereditary forms, autosomal recessive and dominant, which are caused by epithelial sodium channel and mineralocorticoid receptor mutations. Systemic pseudohypoaldosteronism pha type i is a rare genetic disorder resulting from mutations in the subunits of the epithelial sodium channel that manifests as severe salt wasting, hyperkalemia, and metabolic acidosis in infancy.
Pseudohypoaldosteronism pha is a condition that mimics hypoaldosteronism. The molecular defect involved in the systemic autosomal recessive form of the syndrome has been identified. Aug 30, 20 type 1 pseudohypoaldosteronism pha is a rare heterogeneous group of disorders characterised by resistance to aldosterone action. Stockand department of physiology, university of texas health science center at san antonio, san antonio, texas. Autosomal dominant pseudohypoaldosteronism type 1 genetic.
Type i pseudohypoaldosteronism pha 1 is a rare salt wasting syndrome occurring soon after birth, characterized by apathy and severe dehydration accompanied by hyponatremia, hyperkalemia, and metabolic acidosis despite high plasma aldosterone concentrations. Liddles syndrome and autosomal recessive pseudohypoaldosteronism type 1 are rare genetic disorders associated with abnormalities in the function of the collecting tubule sodium channel, also called the epithelial sodium channel enac or the amiloridesensitive sodium channel. The autosomal recessive inherited form of pha1 is characterized by severe multiple target organ resistance to aldosterone, including the kidneys, colon, and sweat. A young child with pseudohypoaldosteronism type ii by a. The disorder involves multiple organ systems and is especially dangerous in the newborn period. Pseudohypoaldosteronism type 1 pha1 is characterized by neonatal salt wasting resistant to mineralocorticoids. Reducing enac expression in the kidney connecting tubule induces pseudohypoaldosteronism type 1 symptoms during k loading soren brandt poulsen,1 jeppe praetorius,1 helle h. Pseudohypoaldosteronism type 1 characterized by marked elevations of plasma aldosterone levels. Pseudohypoaldosteronism type 1 pha is a rare inherited disorder, resulting from end organ resistance to the action of aldosterone. Here, we firstly report on the japanese child of pha. Patients exhibit salt wasting in the neonatal period with failure to thrive, vomiting and dehydration, associated. Patients typically present in the newborn period, improve with age, and usually become asymptomatic without treatment. Pseudohypoaldosteronism pha is characterized by electrolyte abnormalities due to renal tubular unresponsiveness to aldosterone. Pseudohypoaldosteronism pha type i is a rare salt wasting syndrome caused by aldosterone resistance with two distinct forms.
Type i pseudohypoaldosteronism pha1 is a rare salt wasting syndrome occurring soon after birth, characterized by apathy and severe dehydration accompanied by hyponatremia, hyperkalemia, and metabolic acidosis despite high plasma aldosterone concentrations. The journal publishes original papers and commentaries which have relevance to medicine and allied. In this article we report a patient with systemic pha type i presenting with severe dehydration due to salt wasting at 6 days of life. Type 1 pseudohypoaldosteronism pha is a heterogeneous syndrome characterised by salt wasting resulting from target organ.
Autosomal recessive pseudohypoaldosteronism type 1 is a disorder of. Pseudohypoaldosteronism type 1 genetics home reference nih. It can be subclassified into two distinguishable clinical. Sodium regulation, which is important for blood pressure and fluid balance, primarily occurs in the kidneys.
Pseudohypoaldosteronism type 1 pha1 is characterized by endorgan resistance to aldosterone. The mission of the cmj is to promote the science and art of medicine and betterment of public health. Pseudohypoaldosteronism type 1 and the genes encoding. Wnk isoforms as downstream targets of aldosterone becausewnk1andwnk4mediatebiologic effects that associate with aldosterone, there has been interest in linking. Unique eyelid manifestations in type 1 pseudohypoaldosteronism. Genetic analysis revealed a homozygous mutation of. Enable javascript to view the expandcollapse boxes.
Autosomal recessive pseudohypoaldosteronism type i is a rare lifethreatening disease characterized by severe neonatal salt wasting, hyperkalaemia, metabolic acidosis, and unresponsiveness to. Pha type 1 is a rare disease which can present with renal salt wasting, hypovolemia, hyperchloremic acidosis and hyperkalemia. The enac is a heterotrimeric protein complex consisting of. Pseudohypoaldosteronism type 1 pha1, a rare disorder of infancy, presents with potential lifethreatening salt wasting and failure to thrive. Children presented with failure to thrive, dehydration, and electrolyte disturbances are often misdiagnosed to have congenital adrenal hyperplasia cah. Here, we firstly report on the japanese child of pha ii caused by a mutation of. Autosomal dominant pseudohypoaldosteronism type 1 is a disorder of electrolyte metabolism characterized by excess loss of salt in the urine, failure to thrive and dehydration. Pseudohypoaldosteronism type i is a group of rare hereditary disorders that cause the kidneys to retain too much potassium but excrete too much sodium and water, leading to hypotension. Pseudohypoaldosteronism pha is a rare form of saltwasting syndrome, caused by peripheral resistance to aldosterone. Nephrology grand rounds type 2 pseudohypoaldosteronism. While autosomal dominant mutation of the mr cause renal pha1, autosomal recessive mutations of.
Furgeson and stuart linas division of renal diseases and hypertension, department of medicine, university of colorado, aurora, colorado nephrologists frequently encounter disorders involving aldosterone. Pdf type 1 pseudohypoaldosteronism pha is a rare heterogeneous group of disorders characterised by resistance to aldosterone action. Pdf pseudohypoaldosteronism type 1 in an infant sachith. Pseudohypoaldosteronism type 1 pha1 is further differentiated into, i hereditary forms autosomal recessive and dominant, which are caused by epithelial sodium channel and mineralocorticoid receptor mutations respectively and ii secondary form which is associated with urological problems.
Pseudohypoaldosteronism type 1 pha1 is a rare disease of mineralocorticoid resistance due to lossoffunction mutations in two major components of aldosterone response, the mineralocorticoid receptor and the sodium channel enac. Pseudohypoaldosteronism in a female infant and her family. A discussion on the types, clinical course, and management of pseudohypoaldosteronism type 1 is presented. Pseudohypoaldosteronism type 1 pha1 is a rare disease caused by defective transepithelial sodium transport. New insights into renal potassium, sodium, and chloride handling gregory proctor, md, and stuart linas, md. Type 1 pseudohypoaldosteronism pha is a rare heterogeneous group of disorders characterised by resistance to aldosterone action. Pseudohypoaldosteronism type 1 in an infant mafiadoc. Pseudohypoaldosteronism type 1 pha1 is a condition characterized by problems regulating the amount of sodium in the body. Two modes of inheritance of pha1 have been described. By analysis of linkage in 8 families in which pha type ii showed autosomal dominant transmission, mansfield et al.
Autosomal recessive pseudohypoaldosteronism type 1 is a disorder of electrolyte metabolism characterized by excess loss of salt in the urine and high concentrations of sodium in sweat, stool, and saliva. Mechanisms of type i and type ii pseudohypoaldosteronism seth b. Pseudohypoaldosteronism type 1 secondary to vesicoureteral reflux. It is inherited in an autosomal recessive or autosomal dominant pattern. Pseudohypoaldosteronism type ii pha ii, also referred to as gordon syndrome, is a rare renal tubular disease that is inherited in an autosomal manner. Autosomal recessive pseudohypoaldosteronism type 1.
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