Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Hereditary Salt-wasting tubulopathies

Hereditary salt-wasting tubulopathies, a group of autosomal recessive disorders characterized by hypokalemia, hypotension, and alkalosis due to renal wastage of solutes, includes Bartter and Gitelman syndromes.

Historical Aspects

In 1962, Bartter described a new syndrome characterized by hypokalemia due to renal potassium wastage, alkalosis, elevated plasma aldosterone, and hypertrophy of the juxtaglomerular apparatus. Subsequently hypokalemia associated alkalosis was called Bartter syndrome, but it was not before identifying the molecular background that subtypes, including Gitelman syndrome, could be separated.

Epidemiology

The prevalence of hereditary renal salt wasting syndromes is somewhere between 1:50,000 and 1:100,000.

Differentials

Differential diagnosis includes renal tubular acidosis and familial renal disease mimicking endocrine disorders of salt or water wastage.

Pathogenesis

Different functional alterations in different solute transporters along the distal nephron are responsible for these disorders.

Systematic

Disorders of tubular solute transport
Genetic disorders of proximal tubular function
Hereditary Salt-wasting tubulopathies
Bartter syndrome
Antenatal Bartter syndrome type 1
SLC12A1
Antenatal Bartter syndrome type 2
KCNJ1
Classic Bartter syndrome
CLCNKB
Hypercalciuric hypocalcemia 1
CASR
Hypercalciuric hypocalcemia 2
GNA11
Infantile Bartter syndrome with deafness type 4
BSND
CLCNKA
CLCNKB
Transient antenatal Bartter syndrome
MAGED2
EAST syndrome
KCNJ10
Gitelman syndrome
SLC12A3
Hypomagnesemia
EGFR
Gitelman syndrome
SLC12A3
Hereditary myokymia type 1
KCNA1
Hypomagnesemia with hypercalciuria and nephrocalcinosis
CLDN16
Hypomagnesemia with hypercalciuria and nephrocalcinosis with ocular involvement
CLDN19
Hypomagnesemia with normocalciuria
EGF
Intestinal hypomagnesemia with secondary hypocalcemia
TRPM6
Isolated dominant hypomagnesemia
FXYD2
Renal cysts and diabetes (RCAD)
HNF1B
Renal hypomagnesemia 6
CNNM2
TRPM7
Inherited disorders of calcium balance
Liddle syndrome
Nephrogenic diabetes insipidus
Pseudohypoaldosteronism
Renal tubular acidosis

References:

1.

BARTTER FC et al. (1962) Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. A new syndrome.

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2.

OMIM.ORG article

Omim 241200 [^]
Update: April 29, 2019