Gitelman Syndrome – overview

Gitelman Syndrome – overview

Gitelman syndrome (GS) is an inherited (autosomal recessive) salt-losing kidney disease characterised by:

• Increased potassium loss in the urine
• Hypokalaemia and hypomagnesaemia = low potassium and magnesium (both electrolytes/minerals)in the blood
• Alkalosis = too much alkali in the blood
• Hypocalciuria = not enough calcium in the urine.

The abnormality is in the tubules (in the medulla, inner area of the kidney). Gitelman syndrome is also referred to as familial hypokalemia-hypomagnesemia.

GS may present in childhood, but is more frequently diagnosed in adolescence or adulthood. Symptoms are widely variable both in nature and severity. The commonest are lethargy, transient weakness and/or tetany, paraesthesia, thirst and joint pains.

Blood pressure is usually lower than normal. Sudden cardiac arrest has been reported. Gitleman syndrome rarely causes chronic kidney disease (CKD).

What causes Gitelman Syndrome? (genetics)

Mutations in a gene called SLC12A3, which provides the code to make the NaCl cotransporter (in the distal convoluted tubule, DCT), are found in most GS patients. This is part of the tubule of the kidney as shown in the following diagram.

Gitelman syndrome is similar to two other diseases of the tubules of the kidneys, Barrter and Liddle Syndromes (also shown in the diagram above).

The genetics of GS are described here in more detail: Ravarotto, 2022.

Symptoms

• Lethargy
• Muscle weakness/pain
• Paraesthesia (tingling in hands and feet), tetany (all may be variable/transient)
• Palpitations
• Thirst/polydipsia, salt craving (usually patients prefer salty to sweet treats in childhood)
• Polyuria
• Joint pain
• Diuretic/laxative/PPI use (whether prescribed or over-the-counter).

The symptoms are discussed in more detail here: Graziani, 2010.

Diagnosis

This is made by the combination of medical assessment by a kidney or endocrine (glands) specialist (nephrologist or endocrinologist) and the following characteristic blood tests for electrolytes (minerals), and blood pressure (BP).

• Blood potassium (K; low). High potassium levels are more common in CKD
• Magnesium (Mg; variably low)
• Bicarbonate (>25; high)
• Urine calcium (low)
• BP low but rises with age
• Chronic kidney disease (CKD) is rare.

The complexity of the diagnosis is discussed here: Urwin, 2019,

Treatment

Replace electrolytes (lifelong)
Requirements for K and Mg are variable and should be individually tailored, and may be very high.

• Salt. Encourage liberal addition of salt to food, and a high potassium/magnesium diet
• Potassium. KCl is better than effervescent K. Can be given as tabs or liquid. Usually less symptomatic if K >3. K will not rise until Mg does. SlowK™ and Kay-Cee-L Liquid™ are preferable to SandoK™. SlowK is currently not available. A prescription for “slow release KCL 600 mg” with the dose will enable pharmacists to obtain it
• Magnesium. This is difficult as all Mg preparations cause diarrhoea and they all differ
• Lactate. Magtab SR is slow-release and often better tolerated/more effective, therefore dosage is lower. Also only requires twice a day prescription. A few patients require intermittent intravenous (IV) Mg and/or K boluses; however benefits may be short-lived. Over dosage of K/Mg is very unlikely unless CKD coexists. Patient tolerance is the usual limiting factor.

Doses usually require increase during infections, especially those involving vomiting and diarrhoea. In case of acute tetany, magnesium should be administered intravenously (IV) in hospital, together with K as necessary.

Medication (may be necessary in addition to electrolytes)

• To increase blood K: amiloride, spironolactone/eplerenone, ACE inhibitors/ARBs, beta blockers
• To increase blood Mg: amiloride

These can be useful to decrease electrolyte requirements (K, Mg etc). Doses are often limited by the fall in BP and/or other side effects.

Treatment guidelines are summarised here: Blanchard, 2017.

Other

• Vitamin D (may help Mg)
• Investigate cardiac rhythm symptoms
• Maintain a high salt, magnesium and potassium diet.

Monitoring

• 1-2x per year at a regional hospital kidney or endocrine unit
• 1-3 monthly blood K, Mg and bicarbonate measurements at your GP, more often if there is any instability
• At each visit, symptoms related to hypokalemia (fatigue, muscle weakness, constipation, cardiac arrhythmias) and hypomagnesaemia (tetany, cramps, paraesthesia, joint and muscle pain) should be evaluated.

Patient self-care

GS patients should be encouraged to keep their own blood results, using Patients Knows Best, PKB; and increase K/Mg doses if unwell. Like people with diabetes, most can learn to self-manage as long as data are available to them. Daily activities may be symptom-limited and some occupations are unsuitable (e.g. active armed forces, pilot).

Summary

We have described an overview of Gitelman Syndrome. We hope it has been helpful.

Other resources

There is a specialist clinic for patients with GS (and similar syndromes) in Cambridge. It would be a good idea to be seen there at least once.
Here is more information on Gitelman Syndrome.
This is a Gitelman Support Group in the UK.