Gitelman Syndrome Information for Medical Personnel

Gitelman’s Syndrome was discovered in 1966 by Dr Hillel Gitelman. It was discovered that some patients with Bartter’s showed a different myriad of symptoms. Gitelman’s syndrome is also a renal salt wasting disorder but the defective tubule is in the thiazide-sensitive Na-Cl cotransporter in the distal convoluted tubule(DCT). Both disorders are associated with hypokalemia, renal potassium wasting, activation of the renin-angiotensin-aldosterone axis, and normal blood pressure. Unlike patients with Bartters, patients with Gitelman’s syndrome have hypomagnesemia, increased urinary magnesium, and decreased calcium excretion.

Gitelman’s syndrome is characterized by a milder and later clinical presentation. Often, this disorder is diagnosed in asymptomatic adults who present with unexplained hypokalemia. Pediatric cases typically present in the school age period with fatigue, muscle weakness, and symptoms of neuromuscular irritability. Growth retardation and polyuria-polydipsia are not prominant features of Gitelman’s syndrome. Joint pain secondary to chondrocalcinosis has been described in this subset of patients and attributed to the hypomagnesemia.

In terms of laboratory data, Gitelman syndrome is distinguished by high plasma renin activity with normal aldosterone secretion rates, normal urinary prostaglandin excretion, hypocalciuria and usually marked hypomagnesemia. In experimental studies, magnesium deficiency alone has been shown to cause neuromuscular irritability, including postitive Chvostek and Trousseau signs, tremor, fasciculations, and tetany. Moreover, both experimental and clinical data demonstrate that hypomagnesemia blunts the secretion of parathyroid hormone (PTH) and impairs its peripheral action. Binachetti determined that the blood ionized calcium was significantly lower in a cohort of Gitelman patients than in controls. Thus, the neuromuscular irritability evident in Gitelman syndrome probably reflects the combined effects of hypomagnesemia, alkalosis, and dysregulated calciotropic hormone metabolism.

Frequency

Gitelman’s is more common than Bartter’s but is still a rare disorder. There is no racial predisposition for either Bartter’s or Gitelman’s. Bartter’s and Gitelman’s syndromes are inherited as autosomal recessive syndromes; there is no gender preference.

Age

Gitelman’s syndrome is often not diagnosed until adolescence or early adulthood.

Symptoms

  • Hypomagnesemia (With inappropriate magnesuria)
  • Hyponatremia
  • Increased Plasma Renin Activity
  • High or normal aldosterone levels
  • Hypocalciuria
  • Hypokalemia
  • Fatigue
  • Muscle cramps
  • Tetany
    Heart Palpitations
  • Normal Urinary Prostaglandin Excretion
  • Normal growth and development
  • Neuromuscular Irritability
  • Tremor
    Fasciculations
  • Chronic Dermatitis
  • Metabolic Alkalosis
  • Impaired urinary concentration ability

Pathogenesis

Many of the electrolyte disturbances evident in Gitelman syndrome are also observed with administration of thiazide diuretics, which inhibit the Na-Cl cotransporter response to intravenous chlorothiazide but a prompt natiuresis following furosemide administration. These observations indicate that Gitelman syndrome may result from a loss of function in the DCT Na-Cl cotransporter.

Loss of TSC function would cause defective Na and Cl reabsorption in the DCT, which normally reabsorbs approximately 7% of the filtered NaCl load.

The precise mechanism causing hypocalciuria and hypomagnesemia in Gitelman syndrome is unclear.

Treatments

  • Magnesium Supplements
  • Potassium Supplements
  • Spironolactone
  • Amilioride
  • Triamterene

Prognosis

Gitelman syndrome is a more benign disorder and prognosis for normal growth and neurointellectual development is excellent.

Also according to Dr Gitelman patients with Gitelman’s Syndrome have chronically low potassium and Mg levels. Their bodies learn to adapt to these low levels. So many patients live with this for years before diagnosis. To try and get these patients to a normal K and Mg level may be impossible. It is better to focus on alleviating their symptoms. Many patients feel good and do well with a subnormal K and Mg level. What is considered a normal level in a healthy patient may be impossible to achieve in a patient with Gitelman’s syndrome and will only lead to discouragement. Focus on alleviating the symptoms instead of focusing on the lab values.

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