Pediatr Radiol (1992) 22:315-316
Pediatric Radiology 9 Springer-Verlag 1992
Maternal renal insufficiency: a cause of congenital rickets and secondary hyperparathyroidism T. L. Levin ~, L. States 1, A . Greig 2, and H. S. G o l d m a n ~ Department of Radiology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, USA 2Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, USA Received: 4 February 1992; accepted: 8 April 1992
Abstract. We present a case of a newborn with congenital rickets and radiographic evidence of secondary hyperparathyroidism in which the infant's mother had severe, longstanding untreated renal insufficiency. Congenital rickets, a well recognized entity in the early 1900% is now uncommon, with few reported cases in the recent pediatric and radiologic literature. Its occurrence has been described in infants of mothers with severe malnutrition [1, 2], malabsorption syndromes [3], preeclampsia [4] hypoparathyroidism [5] and in the infant of a mother on hemodialysis for chronic renal failure [6]. We report a case of congenital rickets and radiographic changes consistent with secondary hyperparathyroidism, occurring in the infant of a mother with severe untreated renal insufficiency.
Case report A premature male infant was born to a 22year-old woman with focal glomerulosclerosis and severe tubulointerstitial nephritis, diagnosed by renal biopsy 16 months prior to delivery. The mother received no prenatal care and presented in preterm labor in her 23rd week of pregnancy, 4 weeks prior to delivery. Maternal biochemical studies initially revealed hypocalcemia (6--7 mg/dl; normal 8.5-10.5rag/all), hyperphosphatemia (4.55.0 mg/dl;normal2.5-4.5 mg/dl) and elevated alkaline phosphatase (450-500 U/l; normal 30-115U/1). BUN and creatinine were 55 mg/dl (normal 10-26 mg/dl) and 5.1 mg/dl (normal 0.5-1.5 mg/dl) respectively and creatinine clearance was llcc/min (normal 125 cc/min). The mother received 0.25 mg p.o. of Rocotrol per day and 650 mg of calcium chloride p.o. 3 times daily for three weeks with little change in her laboratory values. The 1087 g infant was born by spontaneous vaginal delivery at 27 weeks gestation. Radiographs taken on the first day of life revealed
osteopenia, rib fractures, incomplete and disorganized metaphyseal calcification of the proximal humeri (Fig. la, b) distal femora and proximal tibiae, and subperiosteal bone resorption (Fig. 2). These changes were interpreted to indicate the presence of hyperparathyroidism secondary to hypocalcemia (rickets). Initial biochemical studies of the infant revealed a calcium of 8.0 mg/dl (normal 9.010.6mg/dl) [7], alkaline phosphatase of 225 U/1 (normal 50-155 U/l) [7], and a phosphorus level of 5mg/dl (normal 5.410.9 mg/dl) [7]. Alkaline phosphatase isoenzyme fractionation to exclude hypophosphatasiawas normal.Aparathyroidhormone level was not obtained. The infant received intravenous hyperalimentation supplemented with 0.25 mg/kg calcium per day, and progressed to normal oral feedings. The radiographic and biochemical abnormalities improved over several weeks.
Discussion The biochemical abnormalities present in this infant are consistent with the diagnosis of rickets. The radiographic changes are predominantly those of hyperparathyroidism. It must be presumed that the infant's parathyroid response is a result of the infants low calcium level as maternal parathyroid hormone, elevated in this case, does not cross the placenta [8]. Secondary hyperparathyroidism has been described in infants with congenital rickets [2, 5]. In one report, radiographs taken at birth demonstrated skeletal findings of both rickets and secondary hyperparathyroidism [5]; in another, skeletal changes of hyperparathyroidism followed those of rickets [2]. The radiographs in this case display only the changes of hyperparathyroidism despite the presence of chemical rickets. Possibly the long exposure of the fetus to a hypocalcemic sate was an important factor.
Several factors may have contributed to the development of hypocalcemia in this infant. 80 % of fetal calcium acquisition occurs during the 3rd trimester of pregnancy [9], peaking between 34 and 36 weeks gestation [10]. The infant reported was delivered at 27 weeks gestation and, therefore, did not benefit from the normal 3rd trimester maternal-fetal calcium transfer. In addition, the maternal calcium stores were inadequate due to maternal renal insufficiency. Normally, the level of 1,25 dihydroxycholecalciferol (1,25 vitamin D3), the active from of vitamin D3, rises during pregnancy [8, 9]. As a result, intestinal binding protein synthesis and calcium absorption are increased [8]. Calcium homeostasis is thereby maintained despite demands from the growing fetus. The formation of 1,25 vitamin D3 depends on hydroxylation of its precursor by the kidney. As a result of the renal disease present in the mother of this infant, formation of 1,25 vitamin D3 was impaired, intestinal calcium absorption was decreased and maternal calcium stores available to the fetus were limited. Congenital rickets has been described in the infant of a mother with chronic renal failure, despite normal maternal serum calcium and phosphorus levels achieved by prenatal treatment with 1,25 vitamin D3. The role of additional factors such as calcitonin, magnesium, other minerals, and the placenta in maintaining normal fetal skeletal mineralization is uncertain [8]. Congenital rickets is uncommonly seen today due to improved prenatal care, particularly prenatal nutrition. Congenital rickets with or without secondary hyperparathyroidism should be considered, however, as a cause of skeletal abnormalities in newborns of mothers with severe metabolic disturbances secondary to chronic renal disease.
316
References
Fig. 1. a Frontal chest radiograph demonstrates rib fractures, metaphyseal irregularity in both proximal humeri and subperiosteal bone resorption, b Magnified frontal view of the left proximal humerus
Fig.2. Frontal view of the right knee demonstrates metaphyseal irregularity and subperiosteal bone resorption involvingthe distal femur, proximal tibia and proximal fibula
1. Moncrieff M, Fadahunsi T (1974) Congenital rickets due to maternal vitamin D deficiency. Arch Dis Child 49:810-811 2. Sann L,David L, Frederich A (1977) Congenital rickets study of the evolution of secondary hyperparathyroidism. Acta Paediatr Scand 66:323-327 3. Begum R, Coutinho ML, Dormandy TL, Yudkin S (1968) Maternal malabsorption presenting as congenital rickets. Lancet I: 1048-1052 4. Zeidan S, Bamford M (1984) Congenital rickets with maternal pre-eclampsia. J R Soc Med 77: 426-3427 5. Gradus D, Le Roith D, Karplus M, Zmora E (1981) Congenital hyperparathyroidism and rickets: secondary to maternal hypoparathyroidism and vitamin D deficiency. Isr J Med Sci 17:705-708 6. Kirk J (1982) Congenital rickets - a case report. Aust Paediatr J 18:291-293 7. Nelson W (1987) Textbook of pediatrics. Saunders, Philadelphia 8. Pitkin RM (1985) Calcium metabolism in pregnancy and the perinatal period: a review. AmJ Obstet Gyneco1151:99-109 9. Cushard WG, Creditor MA, Canterbury JM, Reiss E (1972) Physiologic hyperparathyroidism in pregnancy. J Clin Endocrino134:767-771 10. Campbell D, Fleischman A (1988) Rickets of prematurity: controversies in causation and prevention. Clin Perinatol 15: 879-890 Dr. T. L. Levin Albert Einstein College of Medicine Department of Radiology 1300 Morris Park Avenue Bronx, NY 10461 USA
Pediatric Radiology 9 Springer-Verlag 1992
Maternal renal insufficiency: a cause of congenital rickets and secondary hyperparathyroidism T. L. Levin ~, L. States 1, A . Greig 2, and H. S. G o l d m a n ~ Department of Radiology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, USA 2Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, USA Received: 4 February 1992; accepted: 8 April 1992
Abstract. We present a case of a newborn with congenital rickets and radiographic evidence of secondary hyperparathyroidism in which the infant's mother had severe, longstanding untreated renal insufficiency. Congenital rickets, a well recognized entity in the early 1900% is now uncommon, with few reported cases in the recent pediatric and radiologic literature. Its occurrence has been described in infants of mothers with severe malnutrition [1, 2], malabsorption syndromes [3], preeclampsia [4] hypoparathyroidism [5] and in the infant of a mother on hemodialysis for chronic renal failure [6]. We report a case of congenital rickets and radiographic changes consistent with secondary hyperparathyroidism, occurring in the infant of a mother with severe untreated renal insufficiency.
Case report A premature male infant was born to a 22year-old woman with focal glomerulosclerosis and severe tubulointerstitial nephritis, diagnosed by renal biopsy 16 months prior to delivery. The mother received no prenatal care and presented in preterm labor in her 23rd week of pregnancy, 4 weeks prior to delivery. Maternal biochemical studies initially revealed hypocalcemia (6--7 mg/dl; normal 8.5-10.5rag/all), hyperphosphatemia (4.55.0 mg/dl;normal2.5-4.5 mg/dl) and elevated alkaline phosphatase (450-500 U/l; normal 30-115U/1). BUN and creatinine were 55 mg/dl (normal 10-26 mg/dl) and 5.1 mg/dl (normal 0.5-1.5 mg/dl) respectively and creatinine clearance was llcc/min (normal 125 cc/min). The mother received 0.25 mg p.o. of Rocotrol per day and 650 mg of calcium chloride p.o. 3 times daily for three weeks with little change in her laboratory values. The 1087 g infant was born by spontaneous vaginal delivery at 27 weeks gestation. Radiographs taken on the first day of life revealed
osteopenia, rib fractures, incomplete and disorganized metaphyseal calcification of the proximal humeri (Fig. la, b) distal femora and proximal tibiae, and subperiosteal bone resorption (Fig. 2). These changes were interpreted to indicate the presence of hyperparathyroidism secondary to hypocalcemia (rickets). Initial biochemical studies of the infant revealed a calcium of 8.0 mg/dl (normal 9.010.6mg/dl) [7], alkaline phosphatase of 225 U/1 (normal 50-155 U/l) [7], and a phosphorus level of 5mg/dl (normal 5.410.9 mg/dl) [7]. Alkaline phosphatase isoenzyme fractionation to exclude hypophosphatasiawas normal.Aparathyroidhormone level was not obtained. The infant received intravenous hyperalimentation supplemented with 0.25 mg/kg calcium per day, and progressed to normal oral feedings. The radiographic and biochemical abnormalities improved over several weeks.
Discussion The biochemical abnormalities present in this infant are consistent with the diagnosis of rickets. The radiographic changes are predominantly those of hyperparathyroidism. It must be presumed that the infant's parathyroid response is a result of the infants low calcium level as maternal parathyroid hormone, elevated in this case, does not cross the placenta [8]. Secondary hyperparathyroidism has been described in infants with congenital rickets [2, 5]. In one report, radiographs taken at birth demonstrated skeletal findings of both rickets and secondary hyperparathyroidism [5]; in another, skeletal changes of hyperparathyroidism followed those of rickets [2]. The radiographs in this case display only the changes of hyperparathyroidism despite the presence of chemical rickets. Possibly the long exposure of the fetus to a hypocalcemic sate was an important factor.
Several factors may have contributed to the development of hypocalcemia in this infant. 80 % of fetal calcium acquisition occurs during the 3rd trimester of pregnancy [9], peaking between 34 and 36 weeks gestation [10]. The infant reported was delivered at 27 weeks gestation and, therefore, did not benefit from the normal 3rd trimester maternal-fetal calcium transfer. In addition, the maternal calcium stores were inadequate due to maternal renal insufficiency. Normally, the level of 1,25 dihydroxycholecalciferol (1,25 vitamin D3), the active from of vitamin D3, rises during pregnancy [8, 9]. As a result, intestinal binding protein synthesis and calcium absorption are increased [8]. Calcium homeostasis is thereby maintained despite demands from the growing fetus. The formation of 1,25 vitamin D3 depends on hydroxylation of its precursor by the kidney. As a result of the renal disease present in the mother of this infant, formation of 1,25 vitamin D3 was impaired, intestinal calcium absorption was decreased and maternal calcium stores available to the fetus were limited. Congenital rickets has been described in the infant of a mother with chronic renal failure, despite normal maternal serum calcium and phosphorus levels achieved by prenatal treatment with 1,25 vitamin D3. The role of additional factors such as calcitonin, magnesium, other minerals, and the placenta in maintaining normal fetal skeletal mineralization is uncertain [8]. Congenital rickets is uncommonly seen today due to improved prenatal care, particularly prenatal nutrition. Congenital rickets with or without secondary hyperparathyroidism should be considered, however, as a cause of skeletal abnormalities in newborns of mothers with severe metabolic disturbances secondary to chronic renal disease.
316
References
Fig. 1. a Frontal chest radiograph demonstrates rib fractures, metaphyseal irregularity in both proximal humeri and subperiosteal bone resorption, b Magnified frontal view of the left proximal humerus
Fig.2. Frontal view of the right knee demonstrates metaphyseal irregularity and subperiosteal bone resorption involvingthe distal femur, proximal tibia and proximal fibula
1. Moncrieff M, Fadahunsi T (1974) Congenital rickets due to maternal vitamin D deficiency. Arch Dis Child 49:810-811 2. Sann L,David L, Frederich A (1977) Congenital rickets study of the evolution of secondary hyperparathyroidism. Acta Paediatr Scand 66:323-327 3. Begum R, Coutinho ML, Dormandy TL, Yudkin S (1968) Maternal malabsorption presenting as congenital rickets. Lancet I: 1048-1052 4. Zeidan S, Bamford M (1984) Congenital rickets with maternal pre-eclampsia. J R Soc Med 77: 426-3427 5. Gradus D, Le Roith D, Karplus M, Zmora E (1981) Congenital hyperparathyroidism and rickets: secondary to maternal hypoparathyroidism and vitamin D deficiency. Isr J Med Sci 17:705-708 6. Kirk J (1982) Congenital rickets - a case report. Aust Paediatr J 18:291-293 7. Nelson W (1987) Textbook of pediatrics. Saunders, Philadelphia 8. Pitkin RM (1985) Calcium metabolism in pregnancy and the perinatal period: a review. AmJ Obstet Gyneco1151:99-109 9. Cushard WG, Creditor MA, Canterbury JM, Reiss E (1972) Physiologic hyperparathyroidism in pregnancy. J Clin Endocrino134:767-771 10. Campbell D, Fleischman A (1988) Rickets of prematurity: controversies in causation and prevention. Clin Perinatol 15: 879-890 Dr. T. L. Levin Albert Einstein College of Medicine Department of Radiology 1300 Morris Park Avenue Bronx, NY 10461 USA
