Introduction:
First of all, Gordon syndrome, also known as pseudohypoaldosteronism type II (PHA II), is an uncommon, autosomally inherited condition with an unclear prevalence. Mutations in the WNK1, WNK4, CUL3, or KLHL3 genes are the cause of it. Normal kidney function is otherwise present. However, it is characterized by hypertension, hyperkalemia, hyperchloremic metabolic acidosis, and low plasma aldosterone levels. The development of PHA2 can occur at any age, from early childhood or adolescence to adulthood. The management of PHA II's abnormal blood pressure and electrolyte imbalances typically involves salt restriction and hydrochlorothiazide (HCTZ).
What Is Gordon Syndrome?
Gordon syndrome, also known as pseudohypoaldosteronism type II (PHA II), is a rare condition for which there are no data on prevalence. The 1960s saw the first reports of it. The second instance was described by Richard Gordan as a hypertension and hyperkalemia syndrome with a normal glomerular filtration rate. Normal renal function is the only characteristic; hypertension and hyperkalemia are present. Additional characteristics mentioned were low plasma renin activity, comparatively low serum aldosterone levels, and hyperchloremic metabolic acidosis. It often has a variable age of onset and is inherited as autosomal dominant.
What Are the Effects On Kidney in Gordon Syndrome?
Hyperkalemia and otherwise normal renal function are the hallmarks of PHA II, also known as Gordon syndrome, a rare genetic condition. Hypertension, metabolic acidosis, and hyperchloremia are commonly linked to it. Given the severity of hyperkalemia, aldosterone concentrations are variable but typically low, and plasma renin activity is low or low-normal. In contrast, aldosterone resistance is linked to pseudohypoaldosteronism type I.
Mutations in the regulators of the thiazide-sensitive Na+-Cl-Co-transporter (NCC) cause Gordon syndrome, also known as pseudohypoaldosteronism type II or familial hyperkalemic hypertension. These regulators include the "With No lysine [K]" kinases (WNK1 and WNK4, both autosomal dominant), KeLcH-Like3 (KLHL3, autosomal dominant or recessive), and CULlin3 (CUL3, autosomal dominant). The following describes the pathophysiology of metabolic acidosis and hyperkalemia in Gordon syndrome.
In the physiological setting, Na+-Cl-Co-transporter (NCC) is expressed in the distal convoluted tubule's apical membrane and participates in the reabsorption of 5–10% of filtered NaCl. K+ secretion occurs in the collecting duct's main cells through the ATP-dependent K+ channel ROMK. Through oxidative stress-responsive gene 1 (OSR1) or Ste20-related proline–alanine–rich kinase (SPAK), WNK1 and WNK4 raise the phosphorylation and expression of Na+-Cl-Co-transporter (NCC) on the apical membrane. The DCT distal convoluted tubule reabsorbs more NaCl as a result of this. Potassium secretion via ROMK is likewise lowered as a result of the decreased more distal NaCl reabsorption by Epithelial sodium channels (ENaC). Ultimately, the cullin-RING ligase (CRL) complex, which is formed by the proteins produced by the KLHL3 and CUL3 genes and the "really interesting new gene" (RING), mediates the ubiquitination and proteasomal destruction of WNK1 and WNK4 proteins.
What Is Cause of Kidney Disease in Gordon Syndrome?
It is unclear how common PHA II is. Although autosomal recessive inheritance is also possible, autosomal dominant inheritance is more common. It is also called familial hyperkalemic hypertension since there is a strong family history of comparable results. Pathogenic variations of the WNK1, WNK4, CUL3, or KLHL3 genes are linked to it. Mutation in WNK1, WNK4, CUL3, or KLHL3 genes causes aberrant serine/threonine kinase proteins that impact the distal nephron's thiazide-sensitive sodium chloride cotransporter. PHA II can develop at any age, starting in infancy and lasting until maturity.
The distal nephron's thiazide-sensitive sodium-chloride cotransporter is thought to be impacted by aberrant serine/threonine kinase proteins, which is the theory behind the pathophysiology of PHA II. This causes a decrease in potassium and hydrogen excretion in the distal nephron, which causes hyperkalemia and metabolic acidosis, as well as an increase in sodium and chloride reabsorption that causes hypertension and hyperchloremia.
What Are The Diagnostic Standards For Gordon Syndrome?
For PHA II, there are no official diagnostic standards. The most consistent finding is hyperkalemia without impaired renal function; other findings include metabolic acidosis, hyperchloremia, low plasma renin levels, variable serum aldosterone levels (relatively low in the setting of hyperkalemia), hypertension (which can be absent), and hyperchloremia. These findings should raise suspicions in individuals, children, or adults. In certain cases, hypercalciuria has been reported. Short stature, myalgias, periodic paralysis, and irregular teeth are among other features associated with this disease that have been recorded. Although a family history of similar observations is typically present, the diagnosis can nevertheless be made in the absence of a family history. Molecular genetic testing, which detects pathogenic variations of the WNK1, WNK4, CUL3, or KLHL3 genes, can aid in the diagnosis. In addition to these clinical symptoms, laboratory results, and family history are also included. The results from the laboratory options include
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Low or low-normal plasma renin activity.
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Low serum aldosterone levels (in relation to hyperkalemia).
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Hyperchloremic metabolic acidosis.
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Hypercalciuria (sometimes).
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Normal kidney function and glomerular filtration.
How To Manage Kidney Disease in Gordon Syndrome?
PHA II is managed with blood pressure control, genetic counseling, correction of electrolyte imbalances, and prevention of secondary problems. Thiazide diuretics restore electrolyte abnormalities and control blood pressure, typically in a week or less. In order to maintain appropriate blood pressure control and lower the risk of secondary consequences like cardiovascular disease, renal disease, or stroke, extra antihypertensives may occasionally be employed. The patient will look after blood pressure and electrolyte assessments every six months to a year. The patient should refrain from consuming too many foods heavy in potassium and sodium. It is advised to assess relatives who are at risk using blood pressure and serum potassium levels in order to start therapy as soon as possible. Patients should have access to genetic counseling so they may make educated decisions.
Supervisory correction of problems related to electrolytes, reduction of salt, and thiazide diuretics.
Conclusion:
Gordon syndrome, also known as PHA II, is a rare hereditary illness whose frequency is unknown. Strong genetic predominance characterizes it, and it typically runs in families. In the context of normal kidney function, it disrupts Na-Cl cotransporters in the distal nephron and causes increased sodium and chloride reabsorption, which in turn causes hypertension, hyperchloremia, hyperkalemia, and metabolic acidosis. The primary goals of care are to control hypertension, typically with thiazides, and address problems related to electrolytes.
Gordon syndrome, also known as PHA II, is an uncommon illness without a distinct clinical manifestation and murky diagnostic standards. Patients with hypertension and hyperkalemia who also have normal glomerular filtration should be highly suspected of it.
