| Abstract|| |
Although hypercalcemia and hypercalciuria are known to occur in breast-fed pre-term infants, to the best of our knowledge, it has never been reported in a term baby previously. We report a term male baby who was followed-up during pregnancy for having bright kidneys, but a follow-up renal ultrasound (US) after birth had revealed normal scan. Laboratory investigations revealed normal serum calcium (Ca), phosphorous (PO 4 ) and alkaline phosphatase (ALP). The baby was being fed by breast milk. Follow-up US two months later showed early nephrocalcinosis along with hypercalcemia and hypercalciuria; by the age of three months, nephrocalcinosis was more extensive and the serum Ca level was more than 12 mg/L with hypercalciuria. Parathyroid hormone (PTH), phosphorous (PO 4 ), ALP and thyroid function tests were all normal. Antenatal history revealed a hypothyroid mother who was maintained on L-thyroxin, calcium and vitamin D supplement during pregnancy. Her blood tests showed normal serum Ca, low PO 4 and elevated PTH. The baby was diagnosed to have hypercalciuria and hypercalcemia secondary to maternal hypophosphatemia (maternal vitamin D deficiency). Breast feeding was stopped and the baby was started on formula, whereby he showed remarkable improvement both for his blood chemistry as well as his hypercalciuria.
|How to cite this article:|
Hazza IA, Ghandour MS, Almardini RI, Haddad RE, Salaita GM. Hypercalcemia, hypercalciuria and nephrocalcinosis in a breast-fed term newborn: A rare presentation. Saudi J Kidney Dis Transpl 2014;25:849-53
|How to cite this URL:|
Hazza IA, Ghandour MS, Almardini RI, Haddad RE, Salaita GM. Hypercalcemia, hypercalciuria and nephrocalcinosis in a breast-fed term newborn: A rare presentation. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2021 Dec 8];25:849-53. Available from: https://www.sjkdt.org/text.asp?2014/25/4/849/135178
| Introduction|| |
Hypercalcemia may occur within hours after birth or may be delayed for weeks or months. It may result from increased intestinal or renal absorption of calcium, increased bone turnover or iatrogenic causes. 
Hypercalcemia is defined as serum calcium level above 11 mg/L (2.75 mmol/L) or when the ionized calcium is greater than 1.4 mol/L (5.6 mg/dL), and is seen in many disorders such as subcutaneous fat necrosis, William's syndrome, congenital hyperparathyroidism and Bartter's syndrome.  Hypercalcemia may occur in a breast-fed pre-term infant due to feeding with low-phosphate milk.  In this report, we describe a case of neonatal hypercalcemia, hypercalciuria and nephrocalcinosis in a full-term baby fed with low-phosphate breast milk as his mother had hypophosphatemia. Hyper-calcemia and hypercalciuria are known to occur in breast-fed pre-term infants, but we believe that this patient is the first case of a term baby to be reported with this problem.
| Case Report|| |
A. B. is a 2-month-old baby, born full term by vaginal delivery, with a birth weight of 4.1 kg. During antenatal care, his mother was diagnosed to have hypothyroidism although she was asymptomatic. She was being treated successfully with L-thyroxin, calcium (Ca) and vitamin D supplement (400 IU) daily. Intra-uterine fetal ultrasound had shown mild poly-hydramnios and bright fetal kidneys. Laboratory investigations one day after birth revealed normal complete blood count, normal kidney function test, serum Ca of 9.1 mg/dL and normal renal ultrasound. He was maintained exclusively on breast milk. At the age of seven days, follow-up investigations were repeated that showed a serum Ca of 12.7 mg/dL, with urinary spot calcium to creatinine ratio (Ca/Cr) of 1.22. Follow-up kidney ultrasound at the age of two weeks showed a diffuse increase in medullary echogenicity [Figure 1], suggestive of early medullary nephrocalcinosis. At the age of two months, he was referred to Queen Rania Abdulla Children hospital for further evaluation. On admission, he was looking well with weight and height on the 50 th percentile for age, BP was normal on the 85 th percentile for age, sex and height, there has no dysmorphic features, he was well hydrated, with normal cardiac examination and the rest of the physical examination was normal. Investigations revealed serum Ca of 11.5 mg/dL, PO 4 of 4.7 mg/dL, urinary Ca/Cr ratio of 1.86 (hyper-calcuria), alkaline phosphatase (ALP) of 385, HCO 3 level of 24, parathyroid hormone (PTH) of 6 pg/mL (low), Cr of 0.3 mg/dL, blood urea nitrogen of 10 mg/dL, Na of 135 meq/L and K of 4.2 meq/L. 2D-echocardiogram was normal, with normal skeletal survey [Figure 2]a and b. Maternal serum Ca was 9.09 mg/dL (normal), phosphorus was 2.75 mg/dL (low) and the PTH level was 71 pg/mL (high). The maternal vitamin D level was 5.8 ng/mL, which shows severe deficiency. Renal ultrasound (US) of the baby showed medullary nephrocalcinosis. A diagnosis of neonatal hypercalcemia secondary to low-phosphate breast milk was considered, which was confirmed by the low-phosphorous breast milk of 0.9 mg/dL and calcium of 15 mg/dL (maternal breast milk usually contains 27-32 mg/dL calcium and 14-15 mg/dL phosphorous). 
|Figure 1: Initial renal ultrasound showing increased renal medullary echogenecity.|
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The baby was managed by saline and furo-semide for his hypercalcemia and was shifted to formula milk and breast feeding was stopped.
On discharge, he showed normal serum Ca of 9.4 mg/dL, phosphate of 4.3 mg/dL and Ca/Cr in the urine of 0.7 (normal ratio for age).
On a follow-up visit two months after diagnosis, the baby was thriving well. Laboratory evaluation showed serum Ca of 10.4 mg/dL, PO 4 of 6.7 mg/dL, ALP of 276 IU/L and urinary Ca/Cr of 0.57. Ultrasound examination showed mild changes of nephrocalcinosis still being present [Figure 3]a and b. A repeat ultrasound of the abdomen after normalization of serum calcium at the age of six months still showed nephrocalcinosis [Figure 4] which seems as before and not progressing.
|Figure 3: a and b. Ultrasound showing medullary nephrocalcinosis at the age of 2 months.|
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|Figure 4: Repeat ultrasound of the abdomen after normalization of serum calcium shows nephrocalcinosis at the age of 6 months.|
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| Discussion|| |
Many patients with mild hypercalcemia (<12 mg/dL) are asymptomatic. In moderately hyper-calcemic subjects (12-13.5 mg/dL), because calcium acts as an osmotic diuretic, patients have weakness, anorexia, impaired concentration, constipation, polyuria and polydypsia. A severely hypercalcemic child (calcium >13.5 mg/dL) presents with nausea, vomiting, dehydration and impaired consciousness.  They may have failure to thrive. Some patients may have pancreatitis, peptic ulcer and nephrolithiasis.
The causes of hypercalcemia early in life can usually be discerned clinically. It is estimated that history and physical examination along with simple blood tests can provide correct diagnosis with 80-90% accuracy.  In a child with hypercalcemia, baseline total and ionic calcium, phosphorus and urine calcium excretion tests should be performed. A low urinary calcium suggests familial hypocalciuric hyper-calcemia. If urine calcium is elevated, serum PTH should be tested. A high PTH level suggests primary hyperparathyroidism. If it is low, it suggests hypophosphatemia or vitamin D excess. 
Calcium, phosphorous and PTH in both the baby and the mother, and sometimes the father, are needed to differentiate between the different causes as familial hypocalciuric hyper-calcemia associated with heterogeneous inactivating mutation of calcium-sensing receptor.
Primary hyperparathyroidism is the most common cause of asymptomatic hypercalcemia, and the patients may have a family history of multiple endocrine neoplasia (type 1 or 2). The diagnosis is made by demonstrating persistent hypercalcemia in the presence of inappropriately normal or elevated PTH;  in our patient, this cause was excluded by a low PTH level.
Familial hypocalciuric hypercalcemia can cause hypercalcemia in early life. This is a benign disorder characterized by a lifelong hyper-calcemia, normal PTH level and lack of hyper-calciuria. , Neonatal severe hyperparathyroi-dism is a rare cause of hypercalcemia caused by homozygous mutation of the calcium-sensing receptor with feeding difficulties, respiratory distress, hypotonia, failure to thrive and unexplained bone fractures. 
Williams syndrome, characterized by supra-valvular aortic stenosis, elfin-like faces and hypercalcemia,  was excluded by a normal echocardiogram.
Excess intake of calcium with or without excess vitamin D can also cause hypercalcemia; excess vitamin D could be from an exogenous source or from tumor production or granulo-matous diseases. 
Neonatal hypercalcemia due to phosphate depletion usually occurs in low-birth weight babies who are fed unsupplemented human milk that leads to hypophosphatemia, increased renal 1,25(OH)2 vitamin D 3 and increased Ca absorption and suppressed PTH,  which was the explanation of hypercalcemia in our term patient. Sann et al reported hypercalcemia in ten premature infants who were fed with pooled human breast milk and, by analysis of the babies' data, they suggested that hypercalce-mia is related to phosphate-depleted human breast milk in premature infants. 
| Conclusion|| |
Although hypercalcemia in a pre-term baby who is fed with hypophosphatemic breast milk is a well known problem, it may occur rarely in a term baby, and, to the best of our knowledge, it has never been reported in a term baby previously.
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Issa A Hazza
Pediatric Department, Queen Rania Abdulla Children Hospital, Amman
[Figure 1], [Figure 2], [Figure 3], [Figure 4]