|
Gitelman syndrome
Clinical feature:
Definition: Gitelman syndrome is an autosomal recessive inherited renal tubular disorder characterized by potassium und magnesium wastage.
History: 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.
Pathogenesis: Gitelman syndrome results from loss-of-function mutations in the thiazide-sensitive sodium chloride cotransporter gene (SLC12A3).
Epidemiology: The prevalence o heterozygous is at least 1% in the European population. For unknown reasons, children with Gitelman syndrome are much more frequent in families of heterozygous parents.
Clinical picture: 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.
Diagnostics:
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.
Differential: If hypokalemia dominates the clinical picture, other salt wasting disorders including Bartter syndrome have to be considered. Sometimes a compound heterozygous state, one mutation in each of the genes causing either Gitelman or Bartter syndromes, results in a mixed clinical picture. If hypomagnesemia is the leading symptom, other magnesium wasting diseases may be interfering.
|
