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Calcium pyrophosphate dihydrate (CPPD) deposition disease is in most cases idiopathic, but there are familial forms and others in connection with metabolic disease.1 One of the metabolic associations is with hypomagnesaemia, frequently because of Bartter’s syndrome (BS).2 Another cause of hypomagnesaemia is Gitelman’s syndrome (GS),3 a hypocalciuric variant of BS. Recent studies confirm that these are different processes, with diverse molecular bases that explain the clinical and analytical findings characteristic of each one of them.4 We present the case of a patient with chondrocalcinosis (CC) and pseudogout in whose study hypomagnesaemia secondary to GS is detected. In our search of the Medline database, we have not found reports of a similar association. However, reading of some of the CC and BS cases leads us to think that we are actually dealing with patients whose GS had not been diagnosed.5-7
The patient is a 43 year old woman without pathological antecedents who consulted because of a four year history of bilateral mechanic knee pain with episodes of acute arthritis that remitted days after treatment with non-steroidal anti-inflammatory drugs. During four years of follow up she presented with three acute episodes of arthritis affecting the right knee, the left knee, and the right ankle respectively. On one occasion, knee arthrocentesis was carried out and intracellular CPPD crystals were observed in the synovial fluid. Radiographs showed chondrocalcinosis in the knees (fig 1) and pubic symphisis. Table 1 shows the most significant laboratory parameters. The complete blood cell count, hepatic function, serum iron, ferritin, total iron binding capacity, thyroid and parathyroid hormones, and urine analysis were normal.
The patient was normotensive, she denied intake of alcohol, diuretics or any other drugs, she did not have an inadequate diet, and she did not present with any history of vomiting, diarrhoea, tetany, cramps or weakness. Other causes of hypomagnesaemia were excluded and her mother, brother and two children underwent analytic studies. The 83 year old mother had mild hypomagnesaemia and metabolic alkalosis. The 55 year old brother had mild hypokalaemia with serum magnesium in the lower limit of normality. The 18 year old son had normal values and the 24 year old daughter had mild hypokalaemia with serum magnesium in the lower limit of normality. The rest of the parameters and radiographs of knees, pelvis, and wrist were normal. With these data, the patient was diagnosed GS with autosomal dominant transmission and variable phenotypic expression. Oral magnesium lactate treatment (6 mmol/day of elemental magnesium) was started with acceptable gastrointestinal tolerance and mild rise of serum magnesium (0.65 mmol/l) and potassium (3.6 mmol/l) concentrations. After magnesium treatment the values of plasmatic aldosterone and renin were normal. After the start magnesium supplementation the patient has not had any new episodes of acute arthritis.
Arthropathy because of CPPD deposition disease has been described in patients with hypomagnesaemia of renal origin2 8 9 or secondary to BS.10 11 Clinical findings in these cases include CC and recurrent episodes of pseudogout,1 but chronic pyrophosphate arthropathy has been also reported.12 GS is a primary renal tubular disorder and it is considered to be a hereditary variant of BS, its diagnosis being based on the following criteria: (a) hypomagnesaemia of renal origin, (b) hypokalaemia of renal origin, and (c) hypocalciuria.13Other findings in these patients are normotension or hypotension, metabolic alkalosis, hyper-reninaemic hyperaldosteronism and tendency to reduced sodium and plasmatic chloride with inappropriate excretion of sodium and chloride.14
Data in favour of GS diagnosis instead of the classic BS are the age of presentation (adults), lack of frank polyuria, hypocalciuria, and hypomagenesaemia.15 Classic BS and GS are throught to represent distinct tubular disorders: specifically a Henle loop defect in the former and a distal tubule defect in the latter.14Two types of genetic transmission have been suggested in GS, one with autosomal recessive inheritance presenting with frequent tetanic episodes and lower plasma potassium and magnesium concentrations, and one with autosomal dominant inheritance with high phenotypic variability, without tetany and with not so low concentrations of potassium and magnesium.13 The treatment includes potassium and magnesium supplementation, but the use of spironolactone has also been suggested.14 In some patients with CC secondary to hypomagnesaemia, a CC decrease has been observed after continuous treatment with magnesium.7-9 In the present case report good results have been obtained with oral magnesium supplementation.
Since its first description by Bauer in 1979,10 30 patients with BS and CC have been reported. On our review of the Medline literature we did not find any reference to association between CC and GS. It is probable that many of the patients reported as BS actually have GS, as authors do not usually report the data of calciuria.4 The patients reported with both CC and BS have hypomagnesaemia. Some of them also present with hypokalaemia, hypocalciuria, and hypermagnesiuria,5-7 which are the hallmarks of GS.13 In many other cases the values of calciuria are not reported and therefore GS cannot be excluded.
We consider that it is useful to determine plasma bicarbonate, blood and urine ions, urinary magnesium and calcium (urinary calcium/creatinine molar ratio) in all patients with CC and hypomagnesaemia to exclude GS. Also, a screening of family members may be indicated.9 Reports of new cases will lead to a better knowledge of the pathophysiology of both processes.
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