Bartter and Gitelman syndromes: Spectrum of clinical manifestations caused by different mutations

Table 1 Genetics and presentation of Bartter and Gitelman syndromes

Disorder	Gene affected	Gene product	Clinical presentation
Bartter syndrome type I	SLC12A1	NKCC2	Antenatal Bartter syndrome (hyperprostaglandin E syndrome)
Bartter syndrome type II	KCNJ1	ROMK	Antenatal Bartter syndrome
Bartter syndrome type III	ClC-Kb	CLC-Kb	Hypochloremia, mild hypomagnesemia, failure to thrive in infancy
Bartter syndrome type IVA	BSND	Barttin (B-subunit of CLC-Ka and CLC-Kb)	Antenatal Bartter syndrome (hyperprostaglandin E syndrome) and sensorineural deafness
Bartter syndrome type IVB	ClC-Ka and ClC-Kb	CLC-Ka and CLC-Kb	Antenatal Bartter syndrome (hyperprostaglandin E syndrome) and sensorineural deafness
Bartter syndrome type V	CaSR gene	CaSR	Bartter syndrome with hypocalcemia
Gitelman syndrome	SLC12A3	NCC	Hypomagnesemia, hypocalcuria, growth retardation

There are six Bartter syndrome subtypes (I, II, III, IV, IVB, and V) corresponding to six genetic defects. Modified from Seyberth et al[6]. NKCC2: Furosemide-sensitive sodium-potassium-2 chloride cotransporter; ROMK: Renal outer medullary potassium channel; CLC-Kb: Chloride channel Kb; CLC-Ka: Chloride channel Ka; CaSR: Calcium sensing receptor; NCC: Thiazide-sensitive sodium-chloride cotransporter.

Table 2 Features differentiating Bartter and Gitelman syndromes

Features	Classic Bartter syndrome	Gitelman syndrome
Age at onset	Childhood (early)	Childhood or later
Maternal hydramnios	Rare	Absent
Polyuria, polydipsia	Present	Rare
Dehydration	Often present	Absent
Tetany	Rare	Present
Growth retardation	Present	Absent
Urinary calcium	Normal or high	Low
Nephrocalcinosis	Rare	Absent
Serum magnesium	Occasionally low	Low
Urine prostaglandins (PGE2)	High or normal	Normal

Modified from Urbanová et al[20].