Gitelman Syndrome

Gitelman Syndrome (GS) also called familial hypokalemic hypomagnesemic periodic paralysis is a rare autosomal recessive disorder of the kidney that causes excessive loss of electrolytes. The severe deficiency of electrolytes that results can have a wide spectrum of features.

About the disease

The kidneys serve several functions. The primary function is the excretion of toxins by filtering blood and extracting the waste material, which is then excreted in the urine. During this process, the important components in the blood are also exposed to the kidneys excretory process. However, the normal kidney recognises and conserves these components, only disposing off those that are in excess to the body's requirements.

There is a group of diseases called "Renal Tubular Disorders" where this conservation function of the kidneys is lost. These disorders include Bartter Syndrome, Liddle Syndrome, renal Fanconi Syndrome and others. Gitelman Syndrome is one these disorders.

GS is an autosomal recessive disease, meaning one copy of the abnormal gene is inherited from each of the parents. It is therefore more common in communities where consanguinous marriage is prevalent or in communities where population numbers are small and sociocultural norms mandate "inbreeding". Rarely, it may occur as the result of an autoimmune process where the body's immune system malfunctions and starts attacking itself, such as Lupus or Sjogren's Syndrome. GS is a rare disorder, with a prevalence of about 1 per 100,000.

Symptoms

Gitelman syndrome usually becomes apparent anywhere from late childhood (usually over the age of six) to early adulthood. The disorder is highly variable, even among individuals in the same family. Some people do not develop any symptoms (asymptomatic), while others can develop chronic issues that can impact their quality of life.

Many patients have only mild deficiency / no symptoms and hence and go undiagnosed, or are diagnosed incidentally when being evaluated for some other reason.

In symptomatic patients, symptoms are due to electrolyte deficiencies, primarily potassium and magnesium. These include:

• Fatigue
• Failure to thrive
• Tetany
• Seizures
• Muscle Cramps
• Low blood pressure, fainting and dizziness
• Excessive thirst and urination
• Palpitations
• Abnormal sensations (called paresthesias)
• Fainting
• Joint pains (arthralgia)
• Chondrocalcinosis (due to deposition of calciucm pyrophosphate in the joints, resulting in joint destruction)
• ECG abnormalities
• Paralysis
• Abdominal pain, constipations
• Intestinal Obstruction

The symptoms can range from minor to life-threatening.

Diagnosis

The patients who fulfill the below criteria (and also satisfy 10 negative criteria) should be considered for genetic testing.

• Low Potassium (hypokalemia)
• Metabolic alkalosis
• Low Magnesium
• Low levels of calcium in urine (Hypocalciuria)
• High levels of the hormone Renin in the blood
• Elevated chloride excretion
• Blood pressure being low or normal (high blood pressure would suggested other conditions)
• Normal ultrasound (abnormalities on ultrasound suggest other conditions)

Treatment

There is no cure for Gitelman syndrome. The mainstay of treatment for affected individuals is a high salt diet with oral potassium and magnesium supplements. Potassium rich foods such as dried fruit are helpful. Magnesium supplements in single large doses cause diarrhea and should be avoided. Magnesium supplements should be taken in small frequent (4-6 times/ day) in order to avoid magnesium associated diarrhea which may worsen hypokalemia and symptoms of volume depletion. For many individuals, lifelong daily supplementation with magnesium is recommended. In some cases, during severe muscle cramps, magnesium has been given intravenously. In general, the goal of therapy should always be attenuation of symptoms rather than normalization of electrolyte abnormalities.

Source : Directory of Rare diseases

Related resources

1. National Policy for treatment of Rare Diseases
2. Organization for Rare Diseases India