FAMILIAL HYPOMAGNESEMIA-HYPERCALCIURIA WITH NEPHROCALCINOSIS - SEVERE MYOPIA AND HORSE SHOE KIDNEY CAN BE ASSOCIATIONS
Abdulkarim S Almakadma
Department of Pediatrics. KFMC-Childrens Hospital, Riyadh
Address for Correspondence
Abdulkarim S. Al-Makadma, Ass. Professor of Clinical Pediatrics, KFMC-Children's Hospital, Riyadh 11525, P.O.Box 59046.
Email
al_makadma@hotmail.com
Abstract
Many disorders of hypomagnesemia or renal origin are now recognized. Familial Hypomagnesemia, Hypercalciuria and Nephrocalcinosis is one of them. Few patients with this disorder were described in the literatures. The cases of two sisters from a consanguineous marriage with this syndrome are presented. Bilateral nephrocalcinosis in both of them was observed; interestingly one of them has a horse shoe kidney. The Glomerular Filtration Rate in both of them is decreased. The urinary calcium and magnesium were high in both of them where urinary excretion of uric acid and oxalate were normal. Serum magnesium was low in both of them (0.2-0.4 mmol/L) whereas serum calcium, phosphorus and potassium were normal. Serum Parathormone levels were abnormally high. Ophthalmological examination revealed that they have severe myopia with no other eye abnormalities.
Introduction
Varieties of familial hypomagnesemia have been described, including isolated familial hypomagnesemia, Gitelman's syndrome, syndrome of hypokalemia-hypomagnesemia and familial hypomagnesemia-hypercalciuria [1-5]. The cardinal characteristics of the last syndrome include renal magnesium (Mg) wasting with persistent hypomagnesemia unresponsive to magnesium administrations, marked hypercalciuria, nephrocalcinosis and renal insufficiency [2]. We present 2 sisters with familial hypomagnesemia-hypercalciuria along with severe myopia and one sister also having horse shoe kidney.
Case Report
The patients are two sisters of first cousin Saudi parents. The first (elder sister) is 7 years, was referred to the hospital as a case of hyperparathyroidism for further management. Her history revealed that she had polyuria, polydipsia, failure to thrive and repeated urinary tract infections (UTI) since the infancy period. When investigated she was found to have low serum magnesium (0.2mmol/L), normal serum, calcium phosphorus and potassium (Table I). Her urine showed increased excretion of calcium (0.18 mmol/kg/day) and magnesium (0.19 mmol/kg/day) (Table II). The urine oxalates were normal. The Parathormone level was significantly high (101 pg/ml). The creatinine clearance was diminished. Her ultrasound and plain x-ray imaging showed calcinose horse kidney. Renal isotope scanning (DTPA & DMSA) showed impaired renal function and renal scarring respectively. The patient was found to have severe myopia with no other eye abnormalities after full evaluation by the ophthalmologist.

Upon screening the family, we found that her sister (4 years old) almost had the same history but with less frequent attacks of UTI. Her examination revealed that she is severely myopic and has failing to thrive. Her biochemical findings were similar to her sister as shown in Table I and II. Her radiological work up showed that she had bilateral nephrocalcinosis, decreased renal function and scarring of both kidneys (Figure 1). Upon screening, biochemistry was found to be normal in the parents, sister and a brother yet both the mother and the brother were found to be hypercalciuric (Table III). We treated both of our patients with thiazides and oral magnesium. The short term follow up showed no improvement of the serum magnesium but improvement in the Ca/Cr ratio was noted. There was no change in the renal function.

Table 1: Biochemistries of both patients

Blood Sodi
um
mmol
/L
Pota
ssium
mmol
/L
Calci
um
mmol
/L
Magne
sium
mmol
/L
Phos
ph
ate
mmol
/L
Urea
mmol
/L
Creati
nine
mol/L
pH Para
tho
rmo
ne
Pg/
ml
Alka
line
Phos
pha
tase
U/L
TRP
%
Normal
135-
146
3.7-
5.4
2.15
-2.7
0.7-
1.0
1.1-1.8
2.4-6.4
30-80
7.34-
7.43
<60
110-
350
54 ±
23
Patient I
141
3.8
2.17
0.2
1.16
9.3
80
7.4
101
186
50
Patient II
139
3.9
2.34
0.3
1.9
13.8
70
7.42
143
192
45


Table 2: Urine biochemistries in both patients

Urine
Calcium
Mmol/kg/ day
Magnesium
Mmol/kg/ day
Oxalate
Mmol/kg/ day
Ca/Cr
Mmol/mmol
Mg/Cr
Mmol/mmol
Normal
<0.12
0.034
0-0.6
0.2
0.2-0.3
Patient I
0.18
0.14
0.16
1.19
1.18
Patient II
0.27
0.1
0.1
3.1
1.16


Ca: Calcium, Cr = Creatinine, Mg = Magnesium

Table 3: Family Screening

 
Serum-Calcium
2.15-2.7
Serum-Magnesium
0.7-1.1
Calcium/Creatinine
mmol/ mmol
Ultrasound
Kidney
Father
2.4
1.0
0.4
Normal
Mother
2.3
0.83
1.6
Normal
Sister
2.2
0.9
0.3
Normal
Brother
2.5
0.8
2
Normal


Figure 1: Bilateral nephrocalcinosis on ultrasound
Discussion
Few cases of this syndrome were described in the literature. The inheritance of this disorder is autosomal recessive [5]. The two sisters fit the picture of familial hypomagnesaemia hypercalciuria both clinically and biochemically. Both of them have polyuria, polydipsia and repeated UTI. Radiological imaging showed significant nephrocalcinosis in the absence of any evidence or renal tubular acidosis. The first sister was found to have horseshoe kidney as well. This finding was not described as part of the syndrome before. It could be a coincidental finding. Both of them have a degree of renal impairment which was proved biochemically as well as by renal isotope scanning. The rise in parathyroid hormone in both cases was consistent with the degree of the renal impairment. We don't thing that is has a separate role in the mechanism of this disorder. Another finding was the severe myopia which was documented in both cases. Ocular abnormalities had been described as one of the clinical characteristics of this syndrome [2-4].

Existence of a disorder in the reabsorption of magnesium and calcium in the loop of Henle (ascending limb) has been suggested. Data suggests that the primary abnormality in patients with this syndrome is a defect in magnesium and calcium reabsorption at the level of the thick ascending limb of Henle's loop [6]. Calcium receptor gene (CASR) was cloned by the work of the electron microscopy. The receptors were sensitive not only to calcium but to other agonists including magnesium. Later on the CASR was found on the thick ascending limb of the loop of Henle and the gene for that was localized to chromosome 3q13 [7,8].

Neither chronic oral magnesium administration nor thiazide diuretics normalize serum magnesium level or urinary calcium excretions respectively [4]. There is no enough information about long term prognosis of those patients.
Funding
None
Conflict of Interest
None
References :
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  8. Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O, et al. Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature. 1993; 366: 575-580
Last Updated : Tuesday, September 01, 2009 Vol 6 Issue 9 Art #48
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Al-Makadma S A. FAMILIAL HYPOMAGNESEMIA-HYPERCALCIURIA WITH NEPHROCALCINOSIS - SEVERE MYOPIA AND HORSE SHOE KIDNEY CAN BE ASSOCIATIONS. Pediatric Oncall [serial online] 2009[cited 2009 September 1];6. Art #48. Available From : http://www.pediatriconcall.com/Journal/Article/FullText.aspx?artid=259&type=J&tid=&imgid=&reportid=110&tbltype=
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