PEDIATRICS Vol. 106 No. 6 December 2000, pp. 1484-1488

EXPERIENCE AND REASON:
Vitamin D-Deficiency Rickets in Adopted Children From the Former Soviet Union: An Uncommon Problem With Unusual Clinical and Biochemical Features

	ABSTRACT

Top Abstract Introduction Discussion References

Rickets is an unusual disorder in international adoptees. Three international adoptees from the former Soviet Union recently presented with rickets. Their clinical and laboratory presentations were atypical, reflecting circumstances unique to children adopted from orphanages in the former Soviet Union and the early initiation of vitamin D therapy. In these children, radiographs of the long bones were diagnostic when the classically diagnostic biochemical parameters, calcium and 25OHD₃ levels, were normal.

Over the past 20 years, international adoption has become more common in the United States. In recent years, the number of children adopted from the former Soviet Union has increased, and a previously infrequently reported medical problem in international adoptees, vitamin D deficiency rickets, is emerging.¹ Recently, 3 approximately 3-year-old children adopted from orphanages near Moscow presented with vitamin D deficiency. Two presented at the Alfred I. duPont Hospital for Children in Wilmington, Delaware, and one presented at Yale-New Haven Hospital in New Haven, Connecticut. Their clinical and laboratory courses are reviewed. The initial vitamin D levels in these children were performed in the United States, and they reflect vitamin D therapy, not untreated vitamin D deficiency. In 2 of the cases, the bowing in the lower extremities occurred primarily in the ankle area in the distal tibia, not in the knee area in the distal femur classically seen in weight-bearing children with vitamin D deficiency rickets. The radiographic features were diagnostic of rickets, and their resolution with vitamin D therapy supports the diagnosis of vitamin D deficiency.

	CASE REPORTS

Case 1

At age 2 years and 5 months, case 1 presented to the Alfred I. duPont Hospital for Children with bowing of the lower extremities and swelling of the wrists. She resumed walking a few weeks before the evaluation. Her biological mother's pregnancy was complicated by alcoholism. She was born prematurely, but exact gestational age was unknown. Institutionalized from birth, she lived in a hospital for the first 1.5 years of her life and in an orphanage for the next year. Before adoption, she reportedly drank milk without vitamin D fortification. At the time of her adoption approximately 6 weeks before her initial evaluation at duPont Hospital, her adoptive mother started her on a daily multivitamin with 400 international units (IUs) of vitamin D₃ and no supplemental calcium. After her arrival in the United States, she drank a quart of milk per day. Each quart contained 1200 mg of calcium and 400 IUs of vitamin D₃. Over the next 16 months, she ate a well-balanced diet, drank 16 to 32 oz of milk per day, and took a daily multivitamin with 400 IUs of vitamin D₃. Drisdol (vitamin D₂) was prescribed after her initial visit; the daily dose was 500 to 1000 IU vitamin D₂ over the next 16 months.

Her initial physical examination revealed height of 78 cm and weight of 8.14 kg, both well below the 5th percentile for age; swollen wrists; and bowed legs, especially the ankles (Fig 1). Sixteen months later, her height and weight were 90.5 cm and 12.3 kg, both near the 5th percentile. The swelling in her wrists was resolved, and her lower legs were only very mildly bowed.

View larger version (117K): [in this window] [in a new window]   Fig. 1.   Rachitic bowing of the legs, especially at the ankles, in Case 1. A, anterior view; B, lateral view.

Initial laboratory studies revealed normal serum calcium and normal phosphorus levels and an elevated alkaline phosphatase level. Serum 25OHD₃ and parathormone levels were normal. Her serum 1,25(OH)₂D₃ level was elevated. Calcium and phosphorus levels remained normal over the next 16 months. The serum alkaline phosphatase level readily corrected (Table 1). Initial long bone radiographs revealed the classical findings of untreated and treated rickets (Fig 2). Except for mild anterolateral bowing of the tibiae, the rachitic features resolved over the next 16 months (Fig 3).

View larger version (89K): [in this window] [in a new window]   Fig. 2.   Rachitic radiographic features in long bones of legs in Case 1. Widening of long bones. Metaphyseal cupping and beaking of metaphyseal edges. Mild anterolateral bowing of femora. Widening of epiphyseal growth plates. An unusual feature: significant anterolateral bowing of distal tibiae and fibulae.

View larger version (75K): [in this window] [in a new window]   Fig. 3.   Sixteen months later, near resolution of rachitic features in Case 1. Mild anterolateral bowing of the distal tibiae and fibulae.

Case 2

This child presented at Alfred I. duPont Hospital for Children at age 3 years and 3 months with severe lower extremity bowing and swelling of the wrists. She complained of lower extremity discomfort even when walking short distances. For a short period, she even stopped walking. Her biological mother had a full-term pregnancy and spontaneous vaginal delivery. Birth weight was 6 lbs. Because the mother was a severe alcoholic, case 2 was placed in an orphanage where she remained until adoption shortly before her presentation to duPont Hospital. Before adoption, she reportedly drank milk without vitamin D fortification. A few weeks before the child's arrival in the United States, her adoptive mother started her on a daily chewable multivitamin with 200 mg of calcium and 400 IUs of vitamin D₃. After her arrival, she drank approximately a quart of milk per day containing 1200 mg of calcium and 400 IUs of vitamin D₃ per quart. She continued the daily chewable vitamin, consumed 16 to 24 oz of milk per day, and ate a well-balanced diet for the next 2 years.

The initial physical examination at Alfred I. duPont Hospital for Children revealed obvious bowing of the lower extremities and swelling of the wrists. Height and weight were 85.7 cm and 11.6 kg, respectively. Both measurements were less than the 5th percentile for age. There was mild external hip rotation, knee flexion contractures of 25°, and severe anterolateral bowing of the distal tibiae. Initial radiographic skeletal survey revealed evidence of classical severe rickets in her legs (Fig 4), wrists (Fig 5), and chest wall. There was flaring of the distal anterior ribs, creating a rachitic rosary and generalized demineralization. Over the next 4 months, she grew rapidly; her height and weight increased to 90.5 cm and 12.3 kg, respectively. The lower extremity bowing improved greatly. At the time of her last visit, 20 months after her initial visit, her height was 104.5 cm and weight was 16.3 kg. Both measurements plotted on or near the 25th percentile for age. Her physical examination revealed minimal bowing of the lower extremities. Lower extremity radiographs also revealed minimal anterolateral bowing of the tibiae. The growth plates had completely normalized (Fig 6).

View larger version (86K): [in this window] [in a new window]   Fig. 4.   Radiographic rachitic features in long bones of legs in Case 2. Anterior bowing of femora. Irregularity of provisional zones of calcification of distal femora. Irregular and demineralizing distal femoral epiphyses. Anterolateral bowing of distal tibiae and fibulae. Irregularities of provisional zones of calcification of tibiae and fibulae. A, posterior view; B, medial view.

View larger version (95K): [in this window] [in a new window]   Fig. 5.   Radiographic rachitic features in wrists in Case 2. Widening of the distal metaphyses of the radii and ulnae. Irregularities in the provisional zones of calcification of distal radii and ulnae.

View larger version (118K): [in this window] [in a new window]   Fig. 6.   20 months later, near resolution of rachitic features in long bones of legs in Case 2. Minimal anterolateral bowing of tibiae. Normal growth plates. A, posterior view; B, lateral view.

Initial laboratory studies revealed elevated alkaline phosphatase and 1,25(OH)₂D₃ levels and normal 25OHD₃, calcium, and phosphorus levels. Laboratory studies were repeated after 2 months. At that time, alkaline phosphatase was normal. The 1,25(OH)₂D₃ level was lower but still elevated. Laboratory studies were repeated again 2 months later. The 1,25(OH)₂D₃ was then near normal (Table 1).

Case 3

At age 2 years and 10 months, case 3 presented to Yale-New Haven Hospital, New Haven, Connecticut, with significant bowing of his lower extremities and a painful, waddling gait. He entered the United States at the time of his adoption at age 2 years and 8 months. Case 3 was born in Russia and lived most of his life in an orphanage. His fraternal twin sister had rickets; exact details were unavailable. His dietary history before his adoption was unknown. After his adoption, he drank 24 oz of milk daily and often ate cheese and yogurt. He took a daily multivitamin that included vitamin D₃. He was exposed to abundant sunlight.

Two months after his arrival in the United States, his height of 82.5 cm and weight of 11.3 kg were below the 5th percentile. His wrists and ankles were widened, and his chest revealed a rachitic rosary. His femora and tibiae were bowed. At a follow-up visit at his local pediatrician's office at age 3 years and 3 months, his height and weight were 91 cm (5th percentile) and 13 kg (10th percentile), respectively. The femoral and tibial bowing had dramatically improved.

At age 2 years and 10 months, the initial serum calcium and phosphorus levels were normal. Alkaline phosphatase was slightly elevated, and serum 1,25(OH)₂D₃ level was markedly elevated. Serum parathormone was normal. Initial radiographs performed 2 months after arrival in the United States revealed significant rachitic changes. There was flaring of the metaphyses of the tibiae, fibulae, femora, and ribs at the costochondral junctions. The metaphyseal edges of the long bones were poorly defined.

	DISCUSSION

Top Abstract Introduction Discussion References

Vitamin D deficiency rickets has been cited rarely in articles about health problems of children adopted internationally in the United States during the 1980s and 1990s.^2-4 Even in children adopted from Romania, of whom many lived in orphanages for years before adoption, rickets has seldom been mentioned.^5-7 As the aforementioned 3 cases illustrate, vitamin D deficiency rickets is present in the population of institutionalized children adopted from the former Soviet Union. Reportedly, these children have limited sunlight exposure and no vitamin supplementation.

Vitamin D deficiency typically causes prominent bowing about the knee in weight-bearing children. In 2 of the 3 cases presented here, the bowing occurred primarily in the distal tibiae in the ankle area, an unusual feature. The prominent distal tibial bowing most likely was secondary to the posteromedial angulation of the distal tibial growth plate by the lower leg muscles and the minimal weight-bearing. With the introduction of weight-bearing, the prominent bowing shifts from the ankle area to the knee area.⁸

Clinicians should also be aware that the biochemical features typically associated with vitamin D deficiency may be absent. Because calcium and vitamin D levels may be misleading, appropriate radiographic studies should be ordered. Adoptees may receive vitamin supplementation a few weeks to months before their initial medical evaluation in the United States. Their 25OHD₃ levels may be normal, not low, as is classically seen in vitamin D deficiency. Also, their 1,25(OH)₂D₃ levels may be significantly elevated, reflecting vitamin therapy and the compensating stimulus of elevated parathormone levels on 25OHD₃-1-hydroxylase activity seen in the course of vitamin D deficiency until eucalcemia is restored.⁹ Radiographs of the long bones are diagnostic. They reveal classic and healing rachitic changes, even with normal vitamin D, calcium, and parathormone levels. The rachitic changes will gradually resolve over the following 12 to 24 months with adequate vitamin D and calcium supplementation.

Grafton D. Reeves, MD^*
Steven Bachrach, MD
Thomas O. Carpenter, MD^§
William G. Mackenzie, MD
^* Division of Endocrinology
 Division of General Pediatrics
and  Department of Orthopaedics
Alfred I. duPont Hospital for Children
Wilmington, DE 19899
^§ Department of Pediatrics (Endocrinology)
Yale University School of Medicine
New Haven, CT 06504

	FOOTNOTES

Received for publication Feb 29, 2000; accepted Apr 24, 2000.

Reprint requests to (G.R.) Division of Endocrinology, Alfred I. duPont Hospital for Children, Box 269, Wilmington, DE 19899. E-mail: greeves{at}nemours.org

	ABBREVIATIONS

IU, international unit.

	REFERENCES

Top Abstract Introduction Discussion References

1. Albers LH, Johnson DE, Hostetter MK, Iverson S Health of children adopted from the former Soviet Union and Eastern Europe. JAMA. 1997; 278:922-924 [Abstract/Free Full Text]
2. Hostetter M, Johnson DE International adoption: an introduction for physicians. Am J Dis Child. 1989; 143:325-332 [Abstract/Free Full Text]
3. Jenista JA, Chapman D Medical problems of foreign-born adopted children. Am J Dis Child. 1987; 141:298-302 [Abstract/Free Full Text]
4. Hostetter MK, Iverson S, Thomas W, McKenzie D, Dole K, Johnson DE Medical evaluation of internationally adopted children. N Engl J Med. 1991; 325:479-485 [Abstract]
5. Benoit TC, Jocelyn LJ, Moddemann DM, Embree JE Romanian adoption: the Manitoba experience. Arch Pediatr Adolesc Med. 1996; 150:1278-1282 [Abstract/Free Full Text]
6. Johnson DE, Miller LC, Iverson S, The health of children adopted from Romania. JAMA. 1992; 268:3446-3451 [Abstract/Free Full Text]
7. Jenista JA Disease in adopted children from Romania. JAMA. 1992; 268:601-602
8. Harrison HE, Harrison HC. Disorders of calcium and phosphate metabolism in childhood and adolescence. Philadelphia, PA: WB Saunders; 1979
9. Klaus K Pathophysioloogy of calcium metabolism in children with vitamin D-deficiency rickets. J Pediatr. 1995; 121:736-741