Gitelman Syndrome - A Rare Defect in Kidney Function

What Is Gitelman Syndrome?

Gitelman syndrome, often called familial hypokalemia-hypomagnesemia, is an uncommon genetic disorder characterized by abnormalities in kidney function. Gitelman syndrome is a salt-wasting tubulopathy, a disease affecting the renal tubules of the nephron. This condition impairs the kidney's capacity to reabsorb salt, causes alterations in different electrolytes, and constricts extracellular fluid volume. This may lead to symptoms of dehydration. The electrolytes primarily affected are potassium, calcium, magnesium, sodium, and chloride. In the case of Gitelman syndrome, there is a deficiency of potassium in the blood (hypokalemia), elevated pH of the body (metabolic alkalosis), decreased calcium concentration in urine (hypocalciuria), and decreased magnesium level in the blood (hypomagnesemia), and excessive secretion of aldosterone.

The signs, symptoms, and severity of the condition may vary significantly from person to person. The symptoms of Gitelman syndrome can range from mild to severe. These symptoms typically start to manifest in the second decade of life. Gitelman syndrome and Bartter syndrome are two syndromes that are frequently mentioned together. Both conditions are characterized by deficiencies in kidney function that result in volume depletion and similar symptoms.

What Are the Other Names of Gitelman Syndrome?

Other names of Gitelman syndrome are:

• Familial hypokalemia-hypomagnesemia.

• Hypomagnesemia-hypokalemia with hypocalciuria.

What Causes Gitelman Syndrome?

Some of the common causes of Gitelman syndrome are:

• Gitelman syndrome is primarily caused by variations (mutations) in the SLC12A3 gene. SLC12A3 is the gene responsible for providing instructions for producing sodium-chloride cotransporter protein. This protein moves charged atoms of sodium and chloride across cell membranes. Therefore, any variation in this gene can lead to electrolyte imbalances.

• The condition may also occur occasionally due to mutations in the CLCNKB gene. It is the gene responsible for providing instructions for making chloride channels. Therefore, mutations in this gene can lead to impaired chloride channels.

• Mutation in the TRPM6 gene can also lead to the symptoms of Gitelman syndrome. This is because the gene controls the magnesium transport in the distal renal tubules.

• Gitelman syndrome is inherited in an autosomal recessive pattern. Recessive genetic disorders develop when a person receives the same defective gene of the same trait from both parents. A person will be a disease carrier if they have one normal gene and one faulty gene, although they often will not exhibit any symptoms. There is a 25% chance that two carriers will pass the defective gene to their offspring and cause them to be affected. Also, there is a 50% probability of having a carrier child like the parents. Moreover, a child has a 25% probability of inheriting normal genes from both parents and being genetically normal for that trait.

How Common Is Gitelman Syndrome?

• The prevalence of Gitelman syndrome, which ranges from 1 to 10 per 40,000 people and may be higher in Asia, makes it one of the most prevalent inherited diseases of the renal tubules.

• Gitelman syndrome affects both men and women equally.

• The true prevalence of Gitelman syndrome in the general population can be challenging to ascertain because many cases of these conditions may go undetected or be incorrectly diagnosed.

What Are the Symptoms of Gitelman Syndrome?

Some of the common signs and symptoms of Gitelman syndrome are:

• Gitelman syndrome has a wide range of clinical presentations influenced by age, the severity of the symptoms, and metabolic abnormalities.

• The onset of Gitelman syndrome often occurs between late childhood and early adulthood. Even among members of the same family, the condition exhibits considerable variation. While some people can develop chronic conditions that affect their quality of life, others can remain asymptomatic.

• Patients are frequently asymptomatic when diagnosed with hypokalemia in regular laboratory tests, or they could have generalized malaise and fatigue.

• Muscle cramps.

• Low blood pressure (hypotension).

• There have been reports of tetany (a condition caused by low calcium levels) and hypokalemic paralysis, with the latter occurring more frequently in Asian populations.

• Metabolic alkalosis (digestion problems disturb the acid-base balance of the blood).

• Hypokalemia (decreased blood potassium levels).

• Hypocalciuria (decreased calcium concentration in urine).

• Hypomagnesemia (decreased magnesium level in the blood).

• Hyperreninemic hyperaldosteronism (excessive secretion of aldosterone).

• Salt craving.

• Reduced stamina and endurance.

• Episodes of paresthesia (prickling or burning sensation in different body parts).

• Carpopedal cramps (muscular cramps in hands and feet).

• Delayed puberty and retarded growth.

• Short stature.

• Excessive thirst and abnormal drinking behavior.

• Abdominal pain.

• Dizziness, frequent urination (especially at night), joint pain, palpitations, etc.

How Is Gitelman Syndrome Diagnosed?

The diagnosis of Gitelman syndrome is made in the following ways:

Most patients have minimal clinical signs and symptoms. The patient has either normal or low blood pressure, low serum potassium, and low serum magnesium levels. Accordingly, serum bicarbonate is typically high. Aldosterone and plasma renin levels are elevated. Low calcium excretion through the urine.

The following are some suggested biochemical indicators that a patient may have in Gitelman syndrome:

1. Chronic hypokalemia in the absence of potassium-lowering drugs.

2. Presence of metabolic alkalosis.

3. Presence of hypomagnesemia.

4. Presence of hypocalciuria.

5. Low blood pressure.

6. Nephrocalcinosis and other renal abnormalities are absent in renal ultrasonography.

How Is Gitelman Syndrome Treated?

Gitelman syndrome is treated according to the distinctive symptoms that each patient presents. The coordinated efforts of a group of health professionals may be necessary throughout treatment. Affected people and their families may benefit from genetic counseling. Due to its rarity, highly qualified nephrologists may need more experience in detecting or treating this condition.

The treatment of Gitelman syndrome includes:

• Asymptomatic Patients: Asymptomatic individuals frequently do not need therapy but are advised to have outpatient monitoring once or twice a year. They should be aware that they can get dehydrated quickly if they encounter vomiting or diarrhea from a gastrointestinal ailment. During these illnesses, they could need saline and intravenous potassium supplements.

• Diet: Gitelman syndrome patients are advised to eat foods high in sodium chloride. In addition, a high-potassium diet is recommended. Dried fruit is an excellent source of additional potassium. A diet like this can reduce exposure to potassium chloride supplements, which irritates the stomach lining.

• Supplements: A high-salt diet combined with oral potassium and magnesium supplements is the basis of treatment. However, magnesium supplements should not be taken in high dosages because they can cause diarrhea. Magnesium supplements should be taken in modest doses often (four to six times per day) to prevent diarrhea related to magnesium, which can exacerbate hypokalemia and the signs and symptoms of volume depletion. Many patients have to take magnesium supplements for the rest of their lives.

• Medications: Spironolactone, Eplerenone, or Amiloride, classified as potassium-sparing diuretics, may be given to specific patients. These medications are moderate diuretics that prevent the excretion of potassium. While these medications treat hypokalemia, they hardly restore serum potassium levels to normal. Therefore, symptom improvement is the aim of therapy. In case of pain or spasms, non-steroidal anti-inflammatory drugs (NSAIDs) such as Ibuprofen may be helpful.

What Are the Complications of Gitelman Syndrome?

Some of the complications of Gitelman syndrome are:

• Seizures (fits).

• Tetany (tonic spasms and muscle cramps due to physiologic calcium imbalance).

• Ventricular tachycardia (increased heart rate in the heart's lower chamber).

• Rhabdomyolysis (breakdown of muscle tissue leads to tissue content leaking into the blood).

Conclusion

Gitelman syndrome is a rare genetic disorder inherited in an autosomal recessive pattern. The condition is characterized by abnormal kidney function that may lead to an imbalance in the concentration of several electrolytes like calcium, potassium, magnesium, etc. The symptoms of the condition are similar to that of Bartter syndrome. Patients with Gitelman syndrome have an excellent prognosis except for a few people who may be at risk for cardiac arrhythmias. However, how severe their fatigue may significantly impact some patients' everyday activities. This syndrome rarely deteriorates and progresses to renal insufficiency.