Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Gitelman syndrome

Gitelman syndrome is an autosomal recessive inherited renal tubular disorder characterized by potassium und magnesium wastage.

Historical Aspects

In 1966, Gitelman first described a group of patients characterized by hypomagnesemia, hypokalemia, and impaired renal conservation of potassium and magnesium. The resulting clinical symptoms included transient episodes of muscle weakness and chronic non-specific dermatitis. This syndrome was afterwards named hypomagnesemic and hypocalciuric variant of Bartter syndrome, Gitelman syndrome.

Epidemiology

The prevalence of Gitelman syndrome is 1:40,000. Heterozygous carrier constitute at least 1% of the European population. For unknown reasons, children with Gitelman syndrome are much more frequent in families of heterozygous parents.[Error: Macro 'ref' doesn't exist]

Clinical Findings

Gitelman syndrome is considered as a mild disease for unspecific, inconstant, and not-life- threatening symptoms, but the quality of life in these patients is significantly impaired when compared to age and sex matched controls. Patient become symptomatic not before 6 years of age and in most cases only at adult age. Clinical symptoms consist in salt craving, cramps, muscle weakness and aches, fatigue, generalized weakness and dizziness, nocturia, and polydipsia. Blood pressure is below the average. Some patients develop chondrocalcinosis, which is presumably the result of hypomagnesemia induced pyrophosphate crystallization. Laboratory findings include besides hypomagnesemia and hypokalemia an increased renal excretion of both potassium and magnesium, which is in contrast to a decreased renal excretion of calcium. An alkalosis is occasionally found. Patients require potassium and magnesium supplementation. Amilorid might be useful, but should be applied with caution for it further lowers blood pressure.

Diagnosis

The diagnosis is made on the basis of hypomagnesemia and hypokalemia resulting from real wastage of these solutes and contrasted by renal calcium retention. Molecular genetic diagnosis is especially helpful in the many mild cases.

Pathogenesis

Gitelman syndrome results from loss-of-function mutations in the thiazide-sensitive sodium chloride cotransporter gene (SLC12A3).

Symptoms

Hypokalemia
Along with hypomagnesemia, hypokalemia is a cardinal symptom of Gitelman syndrome.
Hypomagnesaemia
Along with hypokalemia, hypomagnesemia is a cardinal symptom of Gitelman syndrome.
Alkalosis
A metabolic alkalosis is rather secondary to potassium depletion.
Hypocalciuria
Hypocalciuria is found if carefully tested for.
Hyperaldosteronism
As in all salt wasting nephropathies a hyperreninemic hyperaldosteronism is observed.
Hypophosphatemia

Systematic

Hereditary Salt-wasting tubulopathies
Bartter syndrome
EAST syndrome
Gitelman syndrome
SLC12A3
Hypomagnesemia

References:

1.

Cruz DN et al. (2001) Gitelman's syndrome revisited: an evaluation of symptoms and health-related quality of life.

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2.

Roser M et al. (2009) Gitelman syndrome.

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3.

Kim JH et al. (2006) SLC12A3 (solute carrier family 12 member [sodium/chloride] 3) polymorphisms are associated with end-stage renal disease in diabetic nephropathy.

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4.

Knoers NV et al. (2008) Gitelman syndrome.

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5.

Gitelman HJ et al. (1966) A new familial disorder characterized by hypokalemia and hypomagnesemia.

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Update: Sept. 26, 2018