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Nutritional Rickets in Suburbia

Department of Pediatrics, Nassau County Medical Center, East Meadow, New York; and Department of Pediatrics, State University of New York at Stony Brook, Stony Brook, New York

Address reprint requests to: Michael T. Pugliese, MD, Nassau County Medical Center, Division of Pediatric Endocrinology, 2201 Hempstead Turnpike, East Meadow, NY 11554

	ABSTRACT

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Objective: Vitamin D deficiency continues to be a problem in pediatrics. This report presents four children, one Caucasian male and three African-American females aged 4 to 24 months who were treated for vitamin D deficiency rickets.

Methods: One female was diagnosed in the Emergency Department during evaluation of a viral syndrome, another presented with hypocalcemic seizures and the third was a self-referral for evaluation of widened wrists. The male had biochemical rickets discovered incidentally during a hospitalization for pneumonia. All were breastfed without formula supplements. The 24-month female had severe cow and soy protein allergies and received multivitamin supplements intermittently. Birth order was from third to sixth child. Two families practiced Islam and the mothers wore veils. The females had a weight deficit for height. The females demonstrated a rachitic rosary, widening of the wrists and leg bowing. At diagnosis the serum calcium was 5.0–8.6 mg/dl, the inorganic phosphorus was 1.5–3.9 mg/dl and the alkaline phosphatase was 408–3324 U/L. The serum intact parathormone levels and the vitamin D levels were measured at Nichols Laboratories. The 25-OH vitamin D levels were 2–22 ng/ml and the 1,25(OH)₂ vitamin D levels were 14–122 pg/ml. All had elevated parathormone levels. The three females had roentgenographic evidence of rickets. Two of the children also demonstrated iron deficiency.

Results: All patients responded to Vitamin D supplements, beginning at 2000 IU for the male and 8,000–10,000 IU daily for the females. Two children were also given calcium supplements. The three females all showed complete healing of the rickets radiologically within six months. The serum intact parathormone demonstrated an inverse correlation with the serum calcium during recovery (r=-0.669; p<0.05).

Conclusion: Vitamin D deficiency does still occur. Breastfed children of multiparous mothers, with increased skin pigmentation, living in the higher latitudes are at increased risk and would benefit from vitamin D supplementation while breastfeeding.

Key words: nutritional rickets, vitamin D deficiency

	INTRODUCTION

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Vitamin D deficiency rickets is a disease entity which was believed to have been eliminated in the United States with the introduction of vitamin D fortification of milk. Unfortunately, vitamin D deficiency rickets continues to be reported in the United States [1–3]. It is seen in children greater than 6 months of age, when exclusive breastfeeding may be unable to meet the vitamin D demands of the growing child. At increased risk are children of African-American backgrounds who live in the inner city regions in the Northern United States where the weather is frequently cloudy [1,3], in children of mothers who observe the Islamic custom of wearing veils [1,3], in children of mothers who practice prolonged breastfeeding and do not or cannot introduce dairy products into the child’s diet [1–4], in the children of vegetarian parents who eschew animal proteins and dairy products [1–3], and in children fed macrobiotic diets [5].

This is a report of four children with rickets. Three of these children meet the traditional profile of rickets in the United States while the fourth child is a case of biochemical rickets diagnosed incidentally.

	MATERIALS AND METHODS

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Case Presentations
Patient #1.
The first patient is a 4-month old white male who was admitted to the hospital for treatment of pneumonia. On admission he was noted to have a serum calcium of 6.4 mg/dl. His birth weight was 3.49 kg. He was born after a full-term, uncomplicated pregnancy and a normal, spontaneous vaginal delivery. He was exclusively breastfed for the first 3.5 months without formula supplementation or vitamin supplements. At 3.5 months of age, cereal and fruit were introduced. The mother stated that since it was winter, she stayed indoors, at home, with the child. He was the third child of his family.

On examination, his length was 65 cm (75th percentile), and weight was 7.0 kg (50th percentile). The head circumference was at the 95th percentile. There was no frontal bossing, craniotabes, rachitic rosary or other bony deformities. Roentgenographic evaluation was normal.

The laboratory studies revealed a borderline elevation of the alkaline phosphatase (408 U/L), which rose to 709 U/L 1 week later (Table 1). The serum magnesium, total protein, albumin and transaminase levels were within normal limits. Iron deficiency was also diagnosed. At that point, vitamin D supplementation, 200 IU in a multivitamin preparation and 600 IU as ergocalciferol, was started.

After 3 months of therapy, the alkaline phosphatase was 244 U/L, the 25-OH vitamin D level was 51 ng/ml and the 1,25 (OH)2 vitamin D level was 115 pg/ml. The vitamin D supplement was discontinued and the child was discharged to the care of the family pediatrician. The child is reported to be growing normally without need for medication.

Patient #2:
The second patient is a 12-month old African-American female who presented to the Emergency Department with seizures. The calcium level was found to be 5.3 mg/dl at presentation.

She had been exclusively breastfed for 11 months and only recently had begun to eat fruit and small amounts of meat. She had not yet begun crawling or attempting to stand. The mother was a practitioner of Islam and wore full veiling which exposed only part of the face and her hands. She was the third child in her family.

On examination, the length was 69.5 cm (5th percentile) and weight was 7.6 kg (<5th percentile). The head circumference was at the 75th to 90th percentile. The exam revealed a 4.0x0.5 cm anterior fontanelle with frontal bossing of the skull. She had eight teeth (four upper, four lower). A rachitic rosary was palpable on the chest. The wrists appeared widened and the ankles were enlarged. Mild bowing of the legs was noted.

Roentgenographic studies revealed rachitic changes.

The laboratory studies at the time of consultation revealed hypocalcemia (5.0 mg/dl), and an elevated alkaline phosphatase of 1392 U/L (Table 1). Iron deficiency was also noted. The serum magnesium, total protein, albumin and transaminase levels were within normal limits.

The child was begun on ergocalciferol, 10,000 IU daily and calcium gluconate orally, 115 mg elemental calcium/kg/day.

Within 3 months, the roentgenography revealed nearly complete healing of the rickets. At this time, the calcium supplement was discontinued. After 6 months of therapy, the long bone roentgenograms showed complete resolution of the rickets and blood studies revealed normal vitamin D levels. Therefore, the ergocalciferol was discontinued. Reassessment of the child during winter, 3 months later, again revealed a low 25-OH Vitamin D level of 8 ng/ml, and a rising alkaline phosphatase (1088 U/L). The history revealed that breastfeeding was still a significant part of the child’s diet. Bone studies revealed no active rickets. The child was restarted on ergocalciferol 1000 IU daily. After this second course, the alkaline phosphatase returned to the normal range at 5 months of follow-up and the ergocalciferol was discontinued. The child was returned to the care of the family pediatrician.

Patient #3:
The third patient is a 16-month old African-American female who presented to the Pediatric Endocrinology Outpatient Center upon recommendation of her pediatrician for evaluation of widened wrists.

She had been exclusively breastfed until 9 months of age. At that time, vegetables, fruit, juice, turkey and cheese were introduced at lunchtime meals. No milk was introduced until the week prior to evaluation. No vitamin supplements had been used. She had begun walking in the past month. Her mother, also, was a practitioner of Islam and wore full veiling, which exposed only part of the face and her hands. She was the sixth child in her family.

On examination, the length was 73.5 cm (5th percentile), and weight was 8.6 kg (5th percentile). The head circumference was at the 10 to 25th percentile. The exam revealed a 2x2.5 cm anterior fontanelle. She had six teeth which were mildly translucent. A rachitic rosary was noted. The wrists appeared widened and the ankles were enlarged. There was mild bowing of the legs.

The roentgenogram revealed severe rickets.

The laboratory studies revealed a calcium of 8.6 mg/dl with hypophosphatemia (1.5 mg/dl) and an elevated alkaline phosphatase (1910 U/L) (Table 1). There was no evidence of iron deficiency on the CBC. The serum magnesium, total protein, albumin and transaminase levels were within normal limits.

The patient was begun on ergocalciferol, 8000 IU daily. Healing was noted by 1 month of therapy on the roentgenograms. The vitamin D supplement was discontinued approximately 6 months later. At that time the alkaline phosphatase was 631 U/L, the 25-OH vitamin D level was 17 ng/ml and the 1,25 (OH)₂ vitamin D level was 103 pg/ml. At 2 years follow-up, the child was at the 50th percentile for height and the 75th–90th percentile for weight. The alkaline phosphatase was 399 U/L.

Patient #4:
The fourth patient is a 24-month old African-American female who was noted to have widened wrists and leg bowing by the Emergency Department physician when she presented with the complaint of weight loss and eczema. She was diagnosed to have rickets and was referred for Pediatric Endocrinology evaluation the following morning. She had been born the 3.82 kg product of a full-term, uncomplicated pregnancy and normal, spontaneous vaginal delivery. She was breastfed without dairy supplement until 9 months of age. Attempted introduction of cow’s milk or soy protein formula resulted in wheezing, diarrhea and eczema. Her diet consisted mainly of juices and table foods without dairy products. She used vitamin supplements intermittently. Prior to the evaluation, the parents had noted the swollen wrists and were concerned about her not attempting to walk. She was the fourth child in her family.

At the time of consultation the length was 74 cm (<5th percentile, height age=12 months) and weight was 8.3 kg (<5th percentile and 87% of ideal weight for height). The head circumference was between the 10th and 25th percentiles.

The child had 12 teeth (six upper, six lower). A rachitic rosary was palpable. The wrists were widened and the ankles swollen. Bowing of the legs was noted. Nummular eczema of the neck, back and legs was present.

Roentgenographic studies revealed rachitic changes.

The laboratory studies revealed a calcium of 8.2 mg/dl, a phosphorus of 3.3 mg/dl and a markedly elevated alkaline phosphatase of (3324 U/L) (Table 1). The total protein, albumin and transaminase levels were within normal limits. A serum magnesium was not obtained. The child was begun on ergocalciferol, 8000 IU daily, and calcitriol, 0.25 mcgm daily. A calcium supplement (115 mg elemental calcium/kg/day) was begun but was discontinued the next day due to a calcium of 9.9 mg/dl. Two days after the above therapy was initiated, the serum inorganic phosphorus fell to 2.7 mg/dl. A phosphorus supplement (30 mg/kg/day) was then also instituted. On the fourth day the calcitriol was discontinued and the calcium supplement reinstituted.

The phosphate and calcium supplements were discontinued after 2 months of therapy. When last seen by the Pediatric Endocrinology service, at 4 months of therapy, the alkaline phosphatase was 749 U/L, the 25-OH vitamin D level was 49 ng/ml and the 1,25(OH)₂ vitamin D level was 283 pg/ml. The bone roentgenograms revealed healed rickets. After this visit the child moved out-of-state and care was transferred to her new pediatrician. Allergy testing identified severe cow’s milk protein and soy protein allergies.

Laboratory Analysis
All bone surveys were evaluated by the same Pediatric Radiologist. The 25-OH vitamin D, 1,25(OH)₂ vitamin D and the intact parathormone levels were sent to Nichols Laboratories for assay.

Statistics
Due to the small number of patients, no statistical methods other than regression analysis for the parathormone levels was utilized. The initial calcium level of Patient #2 was omitted in the analysis.

	RESULTS

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The 25-hydroxyvitamin D levels were low in two children and marginal in the other two. The 1,25 dihydroxyvitamin D level was low in the child with hypocalcemic seizures, normal in the child with biochemical rickets and elevated in the other two patients, compatible with nutritional rickets (Table 1).

The factors which were noted in the children with vitamin D deficiency were: 1) increased skin pigmentation present in three of four of the families; 2) the use of veils which decreased the mothers’ sunlight exposure; and present in two of four families; 3) prolonged, exclusive breastfeeding with either delayed or absent introduction of supplementary dairy products (three of four) or; 4) the inability to introduce dairy products due to milk/soy protein allergies (one of four); and 5) increased birth order, present in all four patients. All the children were the third or later child in their respective families.

Another finding is that there was a significant inverse correlation between the intact parathormone level and the children’s serum calcium (r=-0.669; p<0.05) during therapy.

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
This paper has presented four patients with vitamin D deficiency. One had biochemical rickets while three had overt rickets with bony changes. Unlike most recent reports of vitamin D deficiency rickets in the United States, was the incidental finding of biochemical rickets in a 4-month old exclusively breastfed male. Also, the reports of rickets in the United States do not elaborate on birth order/multiparity, which this paper found to be a factor in the genesis of rickets.

The practice of vegetarianism, which was a factor in 11% [1] to 57% [3] of the other reports was not seen in the four children reported in this paper. Use of rachitogenic medications (i.e., phenobarbital) and parental health beliefs affecting diet which was a factor in only a few of the published cases [1,2], also, was not seen in these children.

A review of three recent reports of nutritional rickets in the United States (Table 2) reveals that the patients presented in this paper are in general agreement with those reports with respect to the fact that overt rickets is a disease of children 6 to 36 months of age [1–3]. Most of the patients were African-American and virtually all were exclusively breastfed without milk or other dairy product supplements. Another contributing factor in common was the maternal observance of the Islamic custom of wearing veils [1,3].

In the second stage, the calcium level is normal and the phosphorus is decreased due to elevated parathormone secretion. In this stage, 1,25-dihydroxyvitamin D levels may be low, normal or even elevated. The alkaline phosphatase is markedly elevated. The data of Patients #3 and #4 are compatible with second stage, or moderate rickets. In the third stage, the calcium and phosphorus are low, the parathormone is elevated and both the 25-OH vitamin D and the 1,25-dihydroxyvitamin D levels are depleted. The data of Patient #2 is most compatible with third stage, or severe rickets.

The finding of biochemical rickets in a 4-month old male suggests that biochemical rickets can occur in breastfed infants less than 6 months of age and highlights the need to insure adequate vitamin D intake in the first 6 months in infants of mothers who elect to exclusively breastfeed. This child had been admitted to hospital for treatment of pneumonia. Of note is that a study from Ethiopia showed that the incidence of rickets was 13-fold higher in children with pneumonia than in controls [6].

Although other US studies of rickets do not comment on family size, the same Ethiopian study quoted above also did find a significant role for birth order and family size in the incidence of rickets [6]. All the patients presented in this paper were the last children in families with three or more children. These families were all larger than the American "average" of 2.3 children.

Of note is that most reports of rickets are from northern US cities (e.g., Seattle, Newark) where sunlight may not be adequate, especially in winter [1,3]. The role of sunlight exposure, latitude, and climate in vitamin D metabolism has been studied.

A study which measured the in vitro photoconversion of provitamin D3 to previtamin D3 revealed that there was significantly less previtamin D3 produced in Ushuaia, Argentina (latitude 55 degrees S) than in Buenos Aires (latitude 34 degrees S) in the given time period during the day [7]. It was shown that children living in extreme southern Argentina had lower 25-OH vitamin D levels and higher parathormone levels in winter than in the summer, and that, in the same group, the dark-complexioned children had lower summertime 25-OH vitamin D levels than the fair-skinned children [8]. A study from South Africa suggested that another factor affecting wintertime vitamin D metabolism is the increased amount of clothing worn in the winter [9].

Only one study [2] reported on the sex of all the patients. In that study they were all males. In this study, the three patients with overt rickets were female. The data are too small for broad conclusions, but this paper is consistent with the finding that disorders of nutrition, in general, are seen more in female children than in males [10].

A misconception concerning vitamin D deficiency is that it is a disease of the inner-city, tenement-dwelling poor. All four of the children in this report were living in lower income suburban communities rather than the inner city.

In a tropical country, such as Nigeria, calcium deficiency, rather than vitamin D deficiency is a significant cause of rickets [11]. Patient #4, who was the patient with the highest 25-OH vitamin D level at diagnosis, was receiving a multivitamin supplement intermittently, which could have raised her vitamin D levels somewhat at the time of diagnosis. However, her diet was devoid of dairy and soy products and calcium deficiency could have been a significant factor in the genesis of her rickets, in addition to poor vitamin D intake [4]. Although, this child was not clinically hypocalcemic at presentation, she developed hypocalcemia in hospital, which worsened after 1 week of ergocalciferol therapy and she did require calcium supplementation for 2 months.

Elevated intact parathyroid hormone levels have been previously described [2,3]. This study went further to monitor the parathormone level during recovery. The parathormone levels were in the left upper quadrant of the total calcium—intact parathormone nomogram used by Nichols Laboratories to report parathormone results. This "area" is the region most values seen in secondary hyperparathyroidism are reported [12]. With the exception of the initial, highly abnormal serum calcium of 5.0 mg/dl seen in Patient #2 which was obtained when the patient had experienced a seizure, all other calcium-parathormone pairs demonstrated a significant correlation during recovery from rickets. The parathormone level fell as the calcium level rose during therapy.

In conclusion, this paper supports the finding that vitamin D deficiency rickets is still a health concern in the northern United States, especially among breastfed children of large families, children of African-American ancestry, children of followers of Islam and children with dairy product intolerance. Identification of children at risk early enough to ensure adequate vitamin D and calcium intakes can help prevent the occurrence of bony changes.

Received April 1, 1998. Accepted May 1, 1998.

	REFERENCES

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7. Ladizesky M, Luz, Oliveri B, San Roman N, Diaz S, Holick MF, Mautalen C: Solar ultraviolet B radiation and photoproduction of vitamin D3 in central and southern areas of Argentina. J Bone Min Res 10: 545–549, 1995.[Medline]
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9. Pettifor JM, Moodley GP, Haugh FS, Koch H, Chen T, Lu Z, Holick MF: The effect of season and latitude on in vitro vitamin D formation by sunlight in South Africa. S Afr Med J 86: 1270–1272, 1996.[Medline]
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