Indian Pediatrics 1999;36:1046-1048
Syndrome of Renal Magnesium Wasting and Nephrocalcinosis
|Rakesh Lodha, Pankaj Hari and Arvind
From the Department of Pediatrics, All India
Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, India.
Nephrocalcinosis, often detected on incidental evaluation, is not an uncommon disorder in hospital practice. The chief causes in children include hyperparathyroidism, distal renal tubular acidosis, idiopathic hypercalciuria and hyperoxaluria. Bartter syndrome, pseudo-hypoaldosteronism and conditions causing hypercalcemia may also be associated with nephrocalcinosis(1). Rarely, an autosomal rece-ssive disorder characterized by persistent hypo-magnesemia, hypercalciuria and ocular abnor-malities may result in nephrocalcinosis(2). We report a similar patient with renal magnesium wasting, who in addition to the features mentioned above had calcification in both basal ganglia.
This 14-year-old girl was admitted with failure to thrive, polyuria and polydipsia since early childhood. Deterioration of vision and multiple episodes of generalized seizures were noted for the last six years. There was no history of arthritis or recurrent urinary tract infections or similar disease in the siblings or parents.
On examination, the child was severely malnourished and stunted, her weight and height being 21.5 kg (< 3rd percetile) and 132 cm (< 3rd percentile), respectively. The blood pressure was normal. She was observed to have thoracolumbar scoliosis, prominent costocho-ndral junction and pectus carinatum. The visual acuity was 6/9 in both the eyes. Both fundi showed macular degeneration. The systemic examination, including that of central nervous system, was unremarkable.
The blood level of urea was 127 mg/dl, creatinine 3.4 mg/dl, sodium 132 mEq/1, potassium 4.7 mEq/1, calcium 9.2 mg/dl, phosphorus 3.8 mg/dl, albumin 4.1 g/dl and alkaline phosphatase 2585 IU/1 (normal <840 IU/1). The arterial blood pH was 7.34 and bicarbonate 22.4 mEq/1; the urine pH was 5.5. The serum magnesium level ranged from 1.3- 1.5 mg/dl (normal 2.0 - 3.0 mg/dl). The serum immunoreactive paratharmone (iPTH) level was 600 pg/ml (normal level 16-46 pg/ml). The levels of thyroxine and thyroid stimulating hormone were normal. Urinary calcium excretion was 74-86 mg per day (urine calcium/creatinine ratio 0.26). The tubular reabsorption of phosphorus (TRP) was 97% (normal 88-98%). The urinary excretion of magnesium was markedly increased to 55-60 mg per day. The fractional excretion of magnesium was 51% (normal <5%). The skeletal survey showed loss of cortical definition with coarse trabecular pattern, normal bone density and presence of subperiosteal bone resorption. These changes were suggestive of renal osteodystrophy. Ultra-sonography of the abdomen revealed normal sized kidneys with bilateral nephrocalcinosis. The electroencephalogram was normal. The computed tomography of the brain was normal except for bilateral basal ganglia calcification.
A diagnosis of syndrome of renal magne-sium wasting with macular degernation, basal ganglia calcification, hypercalciuria, nephro-calcinosis with chronic renal failure was made. The child was treated with calcium carbonate and calcitriol.
The causes of nephrocalcinosis can be separated into three groups: normocalcemic hypercalciuric, hypercalcemic hypercalciuric and normocalcemic normocalciuric. Hyper-calciuria with normal serum calcium is seen in distal renal tubular acidosis. Bartter syndrome, Cushing syndrome, prolonged furosemide therapy, idiopathic hypercalciuria, and syn-drome of renal magensium wasting. Hyper-parathyroidism, hypophosphatasia, rare neo-plasms, William's syndrome and vitamin D intoxication are associated with hypercalcemia, hypercalciuria and nephrocalcinosis. Nephro-calcinosis in the absence of hypercalcemia or hypercalciuria can occur due to hyperoxaluria (primary or short-bowel associated), long-term acetazolamide therapy and as dystrophic calcification(1). Recognition and treatment of the underlying cause is necessary to prevent progression of nephrocalcinosis and renal damage.
The syndrome of renal magnesium wasting is characterized by normocalcemic hyper-calciuric nephrocalcinosis, polyuria, polydipsia, ocular abnormalities (severe myopia, nystag-mus, coloboma, macular degeneration and chorioretinitis), recurrent urinary tract infections and renal stone formation. Hypercalciuria is considered to be the cause of nephrocalcinosis in this disorder. Tetany, seizures, chondro-calcinosis, rickets, hypertension and gouty arthritis have also been described(2-8). The present case showed many of the above features. An additional feature in this patient was bilateral basal ganglia calcification that has been reported in only one case previously(6). The reason for this calcification is not very clear.
Significant urinary magnesium loss (55-60 mg/day, FeMg 51%) in the presence of hypo-magnesemia suggested renal magnesium wasting and ruled out intestinal causes of hypomagnesemia(9). In the presence of hypo-magnesemia, a urine magnesium excretion of more than 25 mg/day indicates renal magne-sium wasting(10). There was no history of intake of drugs(9) and signs and symptoms suggestive of hyperthyroidism were absent. Distal renal tubular acidosis was excluded by the presence of normal blood pH and bicarbo-nate. Normal levels of sodium, potassium and bicarbonate ruled out the diagnosis of pseudo-hypoaldosteronism and Bartter syndrome.
It is suggested that the primary abnormality in the syndrome of renal magnesium wasting is a defect in magnesium and calcium resorption at the level of thick ascending limb of loop of Henle(2,8). The condition is often familial with an autosomal recessive inheritance. Other workers have hypothesized that this has an autosomal dominant inheritance with variable clinical presentation. Isolated hypercalciuria represents a milder expression, and the syndrome of hypomagnesemia, hypercalciuria and nephrocalcinosis, the complete expression of the disorder(8).
Most patients with this condition progress to end stage renal failure(8,11). Medical treatment in the form of thiazide diuretics and magnesium and phosphate supplements, administered early in the disease does not prevent development of chronic renal failure(6). Renal transplantation may result in normaliza-tion of serum magnesium and urinary calcium excretion(8). Recurrence of this condition following transplantation is not reported.
1. Karlowicz MG, Adelman RD. Renal calcification in the first year of life. Pediatr Clin North Am 1995; 42: 1397-1413.
2. Rodriguez-Soriano J, Vallo A, Garcia Fuentes M. Hypomagnesemia of hereditary renal origin. Pediatr Nephrol 1987; 1: 465-472.
3. Meier W, Blumberg A, Imahornk W, De Luca F, Wildberger H, Otliker O. Idiopathic hyper-calciuria with bilateral macular colobomata: A new variant of oculo-renal syndrome. Helv Pediatr Acta 1979; 34: 257-269.
4. Manz F, Scharea K, Janka P, Lombeck J. Renal magnesium wasting, incomplete tubular acido-sis, hypercalciuria and nephrocalcinosis in siblings. Eur J Pediatr 1978; 128: 67-79.
5. Evans RA, Carter JN, George CRP, Walls RS, Newland RC, McDonnell GD, et al. The congenital "magnesium-losing kidney". Report of two patients. Q J Med 1981; 197: 39-52.
6. Ulmann A, Hadj S, Lacour B, Bourdeau A, Brader C. Renal magnesium and phosphate wastage in a patient with hypercalciuria and nephrocalcinosis: Effect of oral phosphate and magnesium supplements. Nephron 1985; 40: 83-87.
7. Torralbo A, Pina E, Portoles J, Sanchez-Fructuoso A, Barrientos A. Renal magnesium wasting with hypercalciuria, nephrocalcinosis and ocular disorders. Nephron 1995; 69: 472-475.
8. Praga M, Vara J, Gonzalez-Parra E. Andres A, Alamoc, Araque A, et al. Familial hypo-magnesemia with hypercalciuria and nephro-calcinosis. Kidney Int 1995; 47: 1419-1425.
9. Agus ZS, Wasserstein A, Goldfarb S. Disorders of calcium and magnesium homeostasis. Am J Med 1982; 72: 473-488.
10. Sutton RA, Domrongkitchaiporn S. Abnormal renal magnesium handling Miner Electr Metab 1993; 19: 232-240.
11. Nicholson JC, Jones CL, Powell HR, Walker RG, McCredie DA. Familial hypomagnesemia, hypercalciuria leads to end stage renal failure. Pediatr Nephrol 1995; 9: 74-76.