|Home | About | Journals | Submit | Contact Us | Français|
A 37-year-old Polish lady presented left knee pain causing reduced mobility and time off work. She also complained of intermittent episodes of fatigue. Knee X-ray showed marked chondrocalcinosis (Figure 1). Serum electrolytes revealed a potassium level of 2.8mmol/l and magnesium of 0.46mmol/l and a hypochloraemic metabolic alkalosis. Urinary electrolytes confirmed renal potassium wasting and hypocalciuria.
The patient’s knee pain was treated with NSAIDs and steroid joint injection and magnesium glycerophosphate and potassium chloride replacement was commenced. Improved serum magnesium and potassium levels were associated with an improvement in both fatigue and joint pain. Genetic testing identified a homozygous mutation in SLC12A3 segregating from both parents, confirming a diagnosis of Gitelman syndrome.
Gitelman syndrome is an inherited tubular salt wasting condition characterised by hypokalaemic, hypochloraemic metabolic alkalosis, hypomagnesemia and a low urinary calcium excretion. The biochemical phenotype mimics chronic thiazide administration. The management of Gitelman syndrome relies on potassium and magnesium replacement and it is often quoted to be a relatively benign condition. However, in reality it can lead to significant co-morbidity with patients complaining of salt craving, nocturia and polyuria and musculoskeletal symptoms such as tetany and cramps, muscle weakness and aches.1 Chondrocalcinosis can affect various joints. Gitelman syndrome patients often complain of extreme fatigue and lethargy which severely impacts upon quality of life.2
In most patients, mutations in SLC12A3 encoding the thiazide sensitive sodium chloride co-transporter underlie this disease. Mutations in CLCNKB encoding the basolateral chloride channel may also give a Gitelman syndrome phenotype.1 The pathophysiological defect is a disruption in reabsorption of sodium chloride at the distal convoluted tubule leading to salt wasting, volume contraction and the activation of the renin-angiotensin-aldosterone system. The volume contraction also results in a compensatory increase in proximal sodium reabsorption and passive proximal calcium reabsorption, which is thought to be responsible for the hypocalciuria. Cell membrane depolarisation in hypokalemic cells is thought to contribute to the reduction in cell magnesium uptake, magnesium wasting and hypomagnesemia.3
The chondrocalcinosis associated with Gitelman syndrome is linked to hypomagnesemia.4 Magnesium is a co-factor for phosphatases including alkaline phosphatase and the hypomagnesemia seen in Gitelman syndrome is therefore thought to result in an increase in the extracellular ionic inorganic pyrophosphate which is a pre-cursor of calcium pyrophosphate crystals. A reduction in magnesium levels also reduces the solubility product of the calcium pyrophosphates. Deposition of these crystals in the articular cartilage results in chondrocalcinosis.3 Magnesium supplementation has been shown to reduce chondrocalcinosis and flares of joint pains.3
Conflict of interest: None declared.