Monday, January 30, 2023
HomePediatrics: General MedicinePseudohypoaldosteronism

Pseudohypoaldosteronism

Background

Pseudohypoaldosteronism (PHA) comprises a heterogeneous group of disorders of electrolyte metabolism characterized by an apparent state of renal tubular unresponsiveness or resistance to the action of aldosterone. It is manifested by hyperkalemia, metabolic acidosis, and a normal glomerular filtration rate (GFR). Volume depletion or hypervolemia; renal salt wasting or retention; hypotension or hypertension; and elevated, normal, or low levels of renin and aldosterone may be observed in the various conditions that result in this syndrome.

Since primary PHA was first described, it has been further subclassified into PHA type I (PHA-I), which is the classic form, and PHA type II (PHA-II), which is also referred to as Gordon syndrome or chloride shunt syndrome. PHA-I itself has been recognized as a heterogeneous syndrome that includes at least 2 clinically distinguishable entities with either renal or multiple target organ defects (MTOD). Early childhood hyperkalemia, or renal tubular acidosis (RTA) type IV subtype 5, is a variant of the renal form of PHA-I.

PHA-II is a rare familial renal tubular defect characterized by hypertension and hyperkalemic metabolic acidosis in the presence of low renin and aldosterone levels. Paver and Pauline first reported PHA-II in 1964,
though it was Gordon who first described it as a new clinical entity in 1970.
In addition to Gordon syndrome, PHA-II includes what is known as adolescent hyperkalemic syndrome.

The molecular basis for most individuals who have PHA-II was linked to loss-of-function mutations in WNK1 or WNK4.
WNKs are a family of serine-threonine protein kinases that have an unusual placement of the catalytic lysine as compared with all other protein kinases. WNK1 or WNK4 regulate chloride cotransporters of the distal nephron and other epithelia.

Characteristics of PHA-I and PHA-II are summarized in the Table below. In addition to the 2 types of primary PHA, an acquired or secondary form of PHA has been described.

Table. Characteristics of Primary Pseudohypoaldosteronism (Types I and II) (Open Table in a new window)

Details

PHA Type I

PHA Type II

Renal PHA-I

MTOD PHA-I

Early Childhood Hyperkalemia

PHA-II

Synonyms

Classic PHA of infancy, Cheek and Perry syndrome, autosomal dominant PHA-I, subtype 4 RTA IV

Autosomal recessive PHA-I

Subtype 5 RTA IV

Adolescent hyperkalemic syndrome, Spitzer-Weinstein syndrome, subtype 3 RTA IV

Gordon syndrome, mineralocorticoid-resistant hyperkalemia, chloride shunt syndrome

Age

Newborn period, infancy

Newborn period, infancy

Infancy, childhood

Childhood

Adulthood

Organs

Kidney

Kidney, sweat glands, salivary glands, colon

Kidney

Kidney

Kidney

Genetics

Autosomal dominant, sporadic

Autosomal recessive, sporadic

Unknown

Unknown

Autosomal dominant, sporadic

Mechanism

Heterozygous MLR mutations (possible)

Defective Na transport in organs that contain ENaC

Maturation disorder in the number or function of aldosterone receptors

Chloride shunt

Chloride shunt

Serum potassium

High

High

High

High

High

Acidosis

Present

Present

Present

Present

Present

Serum sodium

Normal or low

Normal or low

Normal

Normal

Normal

PRA*

High

High

Normal or high

Normal or low

Low

Aldosterone

High

High

Normal or high

Normal or low

Low

Blood volume

Normovolemia, hypovolemia

Normovolemia, hypovolemia

Normovolemia

Hypervolemia

Hypervolemia

Blood pressure

Normal or low

Normal or low

Normal or low

Normal or low

Normal or low

GFR

Normal

Normal

Normal

Normal

Normal

Salt wasting

Renal

Renal, sweat or salivary glands, colon

Absent

Absent

Absent

Hypercalciuria

Present or absent

Absent

Absent

Present

Present

Therapy

Na supplementation, K-binding resins

High-Na, low-K diet, K-binding resins, hydrochlorothiazide

Na bicarbonate, K-binding resins

Dietary Na restriction, hydrochlorothiazide

Dietary Na restriction, hydrochlorothiazide

Prognosis

Outgrow by age 2 y

Lifelong therapy

Outgrow by age 5 y

Lifelong therapy

Lifelong therapy

*Plasma renin activity.

ENaC = epithelial sodium channel; GFR = glomerular filtration rate; MLR = mineralocorticoid receptor gene; PHA = pseudohypoaldosteronism; RTA = renal tubular acidosis.

RELATED ARTICLES
- Advertisment -

Most Popular