Gitelman syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Gitelman syndrome is a kidney disorder that causes an imbalance of charged atoms (ions) in the body, including ions of potassium, magnesium, and calcium.

The signs and symptoms of Gitelman syndrome usually appear in late childhood or adolescence. Common features of this condition include painful muscle spasms (tetany), muscle weakness or cramping, dizziness, and salt craving. Also common is a tingling or prickly sensation in the skin (paresthesias), most often affecting the face. Some individuals with Gitelman syndrome experience excessive tiredness (fatigue), low blood pressure, and a painful joint condition called chondrocalcinosis. Studies suggest that Gitelman syndrome may also increase the risk of a potentially dangerous abnormal heart rhythm called ventricular arrhythmia.

The signs and symptoms of Gitelman syndrome vary widely, even among affected members of the same family. Most people with this condition have relatively mild symptoms, although affected individuals with severe muscle cramping, paralysis, and slow growth have been reported.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Gitelman syndrome is usually caused by mutations in the SLC12A3 gene. Less often, the condition results from mutations in the CLCNKB gene. The proteins produced from these genes are involved in the kidneys' reabsorption of salt (sodium chloride or NaCl) from urine back into the bloodstream. Mutations in either gene impair the kidneys' ability to reabsorb salt, leading to the loss of excess salt in the urine (salt wasting). Abnormalities of salt transport also affect the reabsorption of other ions, including ions of potassium, magnesium, and calcium. The resulting imbalance of ions in the body underlies the major features of Gitelman syndrome.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Gitelman syndrome affects an estimated 1 in 40,000 people worldwide.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Hypokalemia · Very frequent (99-80%)

The concentration of potassium(1+) in the blood circulation is below the lower limit of normal.

Abdominal pain · Frequent (79-30%)

An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.

Failure to thrive · Frequent (79-30%)

Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.

Hypomagnesemia · Frequent (79-30%)

The concentration of magnesium in the blood circulation is below the lower limit of normal.

Muscle weakness · Frequent (79-30%)

Reduced strength of muscles.

Prolonged QT interval · Frequent (79-30%)

Increased time between the start of the Q wave and the end of the T wave as measured by the electrocardiogram (EKG).

Low-to-normal blood pressure · Frequent (79-30%)

Delayed puberty · Occasional (29-5%)

Passing the age when puberty normally occurs with no physical or hormonal signs of the onset of puberty.

Enuresis · Occasional (29-5%)

Lack of the ability to control the urinary bladder leading to involuntary urination at an age where control of the bladder should already be possible.

Glucose intolerance · Occasional (29-5%)

Glucose intolerance (GI) can be defined as dysglycemia that comprises both prediabetes and diabetes. It includes the conditions of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and diabetes mellitus (DM).

Hypermagnesemia · Occasional (29-5%)

The concentration of magnesium in the blood circulation is above the upper limit of normal.

Hypocalcemia · Occasional (29-5%)

The concentration of calcium in the blood circulation is below the lower limit of normal.

Insulin resistance · Occasional (29-5%)

Increased resistance towards insulin, that is, diminished effectiveness of insulin in reducing blood glucose levels.

Metabolic alkalosis · Occasional (29-5%)

Metabolic alkalosis is defined as a disease state where the pH is elevated to greater than 7.45 secondary to some metabolic process.

Other findings in the same source

From: Orphanet

Additional reported features include Muscle spasm (Occasional (29-5%)); Nausea and vomiting (Occasional (29-5%)); Nocturia (Occasional (29-5%)); Proteinuria (Occasional (29-5%)); Renal potassium wasting (Occasional (29-5%)); Salt craving (Occasional (29-5%)); Abnormal T-wave (Very rare (<4-1%)); Arthralgia (Very rare (<4-1%)); Blurred vision (Very rare (<4-1%)); Cerebral calcification (Very rare (<4-1%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Gitelman syndrome is Nephrology, with a nephrologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• How is kidney function being assessed over time?
• Are any current medicines or supplements relevant to kidney safety?
• Is there an individual recommendation about fluids, diet or blood pressure?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Gitelman syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.