Rickets with alopecia-remission following a course of 1-α-hydroxy vitamin D3 therapy

A child is described with rickets and alopecia who did not respond to high doses of vitamin D₃ but who responded to a small dose of 1--hydroxyvitamin D₃. Treatment was continued for 2 years and then stopped. She has not shown any signs of relapse 1 year after stopping treatment. Her alopecia, however, has remained unchanged. One year after stopping treatment, her serum 25-hydroxycholecalciferol and parathormone levels were within normal limits but serum 1,25-dihydroxycholecalciferol was elevated.Abbreviations 25 OH D₃ 25-hydroxycholecalciferol - 1,25 (OH)₂ D₃ 1,25-dihydroxycholecalciferol - 1--OH D₃ 1--hydroxy vitamin D - VDDR II vitamin D dependent rickets type II     

Activity of renal 25-hydroxyvitamin D3-1α-hydroxylase in a case of X-linked hypophosphataemic rickets

In 1974, a 2-year-old boy was diagnosed as having X-linked hypophosphataemic rickets (XLH) because of severe rickets and hypophosphataemia.The vitamin D metabolite concentrations, blood and urine chemistry and renal 25-hydroxyvitamin D₃ (25 OHD₃)-1-hydroxlase were measured in 1982 (about 2 weeks after withdrawal of medication). 1-hydroxylase was 392 pg/mg tissue/20 min in the patient, which was high compared with aged-matched controls (69.7±28.5 pg/mg tissue/20 min, mean ±SD, n=7). Our present studies showed that the 1-hydroxylase activity in the patient with XLH was elevated. Therefore, the normal or low 1,25-dihydroxyvitamin D₃ (1,25-(OH)₂D₃) concentrations in XLH patients could be due to accelerated catabolism of 1,25-(OH)₂D₃ or abnormally regulated 25OHD₃-1-hydroxylase in response to hypophosphataemia, although significantly elevated above that in normal controls.Abbreviations XLH X-linked hypophosphataemic rickets - CPBA Competitive protein binding assay - Al-P alkaline phosphatase - P phosphate     

Vitamin D dependent rickets type II with myelofibrosis and immune dysfunction

We present a new patient with vitamin D dependent rickets type II. A 20-month-old Arabian boy whose parents are first cousins showed florid rickets, myelofibrosis and recurrent septicaemia. In addition to absent specific binding for 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃). 25-Hydroxyvitamin D₃-24-hydroxylase activity could not be induced in cultured fibroblasts. The patient did not respond to 99 g 1,25(OH)₂D₃ per day, but skeletal and haematological abnormalities improved with daily infusion of 100 mg/kg calcium, as serum parathyroid hormone levels fell to normal values. At the age of 7 years, he died from pneumonia. The improvement of haematological abnormalities with calcium infusions but not with 1.25(OH)₂D₃ suggests a pathogenetic relationship of myelofibrosis and hyperparathyroidism. Having antilipid A IgM antibody titres up to 110.000 after Gram negative septicaemias, the patient never produced corresponding IgG antibodies. His neutrophil chemotaxis was persistently reduced to 57%±3% of age-matched controls (P<0.028). The patient showed two pathological immune functions considered to contribute to the well-known susceptibility to infection in rickets.     

25 Hydroxyvitamin D and vitamin E absorption in healthy children and children with chronic intrahepatic cholestasis

Patients with chronic cholestasis have reduced 25-hydroxyvitamin D (25 OHD) and vitamin E levels. We determined serum concentrations of 25 OHD, 1,25-dihydroxyvitamin D [1,25(OH)₂D] and vitamin E before and after oral administration of 10 g/kg body weight 25-hydroxyvitamin D₃ (25 OHD₃) and 100 IU/kg body weight vitamin E, respectively, in 4 patients with intrahepatic cholestasis and 6 healthy children. Vitamin E increased in all controls but in only one of the four patients. In contrast, oral 25 OHD₃ induced a normal rise in circulating 25 OHD and 1,25(OH)₂D. The low serum levels of 25 OHD in the patients before the oral bolus may have been due to inadequate parenteral vitamin D administration and/or to the simultaneous phenobarbital treatment. The latter possibility is supported by the increase of serum 25 OHD into the normal range after withdrawal of phenobarbital in one of the four patients.We conclude that vitamin E has to be supplemented parenterally or in water-soluble oral form. Further studies are necessary to clarify whether high-dose long-term oral 25 OHD₃ supplementation is sufficient to prevent vitamin D deficiency in patients with chronic cholestasis.Abbreviations 25 OHD 25-hydroxyvitamin D - 25 OHD₃ 25-hydroxyvitamin D₃ - 24,25(OH)₂D 24,25-dihydroxyvitamin D - DBP vitamin D binding protein This report was presented in part at the XIX European Symposium on Calcified Tissues in Stockholm, June 1986. This study was supported by the Deutsche Forschungsgemeinschaft Bu-199-9-1     

Two siblings with vitamin-D-dependent rickets type II: No recurrence of rickets for 14 years after cessation of therapy

Rickets in a 3-year-old boy and his 1-year-old sister, both with alopecia, was cured by treatment with 50,000IU of vitamin D₂ daily for 2 years and did not recur within 14 years after cessation of therapy. A diagnosis of vitamin-D-dependent rickets type II was made in these patients at the ages of 20 and 18 years based on the findings that 1,25-dihydroxyvitamin D₃ [1,25 (OH)₂D₃] did not inhibit DNA biosynthesis in phytohaemagglutinin-stimulated lymphocytes and that cultured skin fibroblasts showed impaired nuclear uptake and normal cytosol binding of [³H] 1,25(OH)₂D₃. Surprisingly, the serum 1,25(OH)₂D levels of these patients were high and their serum 24,25-dihydroxyvitamin D levels were low, although neither patient showed any symptoms except alopecia. The presence of vitamin D metabolite imbalances in the absence of rickets in these patients might be explained by differences in sensitivity to 1,25(OH)₂D₃ of bone formation and vitamin D metabolism. In addition, changes of sensitivity to treatment with vitamin D derivatives might be a consequence of differentiation of target cells. From the present findings, it is suggested that in this disease treatment with a sufficient dose of vitamin D derivatives should be initiated in the active phase of rickets.     

Vitamin D-dependent rickets type II: extreme end organ resistance to 1,25-dihydroxy vitamin D3 in a patient without alopecia

Vitamin D-dependent rickets type II (VDDR II) is a rare syndrome resulting in severe rickets and is resistant to treatment with vitamin D and its derivatives. Patient with this disease, who are frequently the children of consanguinous marriages, present with elevated circulating concentrations of 1,25-dihydroxy vitamin D, the active metabolite of vitamin D, and in vitro studies have indicated a failure of intracellular binding of the hormone. Alopecia has been noted in many of these patients and it has been suggested that this feature may indicate a more marked resistance to treatment. However we describe a 3-year-old boy with this disease who, although having normal hair growth, displayed extreme resistance to treatment with active vitamin D metabolites. In vitro studies of skin fibroblasts disclosed not only an absence of hormone binding or 1,25(OH)₂D₃-induced 24-hydroxylase activity but reduced metabolism of 1,25(OH)₂D₃ itself. In this child, treatment with exogenous 1,25-dihydroxy vitamin D₃ at doses of up to 24g/day, which increased the circulating concentration of the metabolite to greater than 100 times the normal adult mean, failed to alleviate his condition and he died at the age of 39 months. This would therefore suggest that absence of alopecia, in this condition, cannot be regarded as a constant predictive sign of a lesser resistance and of responsivenes to Vitamin D treatment.Abbreviations VDDRII vitamin D-dependent rickets type II - AIK Phos alkaline phosphatase     

Vitamin D-dependent rickets type I and type II

Two distinct hereditary defects, vitamin D-dependent rickets type I (VDDR I) and type II (VDDR II), have been recognized in vitamin D metabolism. VDDR I is suggested to be a deficiency of the renal 25-hydroxyvitamin D (25(OH)D)-1α-hydroxylase. Muscle weakness and rickets are the prominent clinical findings. A normal physiologic dose of 1α-hydroxyvitamin D₃ and 1,25-dihydroxyvitamin D₃ is sufficient to maintain remission of rickets in this disorder. VDDR II consists of a spectrum of intracellular vitamin D receptor (VDR) defects and is characterized by the early onset of severe rickets and associated alopecia. This can be attributed to mutations in the VDR gene. Massive doses of vitamin D analogs and calcium supplementation is usually required for the treatment; however, the response to therapy is sometimes variable.     

Early response to vitamin D2 in children with calcium deficiency rickets

OBJECTIVE: To assess the effect of vitamin D(2) administration on serum vitamin D metabolite concentrations in calcium deficiency rickets. STUDY DESIGN: We administered vitamin D(2), 50,000 IU orally to 16 Nigerian children 15 to 48 months of age with radiographically active rickets. We measured calcium and vitamin D metabolites at baseline and at 1, 3, 7, and 14 days. RESULTS: At baseline, ranges of serum 25-hydroxyvitamin D (25(OH)D) concentrations were 18 to 40 nmol/L (7-16 ng/mL), and 1,25-dihydroxyvitamin D (1,25-(OH)(2)D) concentrations were 290 to 790 pmol/L (120-330 pg/mL). After vitamin D administration, serum 25(OH)D and 1,25(OH)(2)D concentrations rapidly rose and peaked at 2.8 and 1.9 times the baseline values (P < .001), respectively, at 3 days. Positive correlations between 1,25(OH)(2)D and 25(OH)D were strongest at day 3 (r = 0.84, P < .001) and weakest at day 14 (r = 0.41, P = .11). The relationship of 1,25(OH)(2)D with 25(OH)D at baseline and the increase in 1,25(OH)(2)D in response to vitamin D were similar to those described in children with vitamin D deficiency. However, unlike the pattern in vitamin D deficiency, 1,25(OH)(2)D remained positively correlated with 25(OH)D after administration of vitamin D. CONCLUSION: Dietary calcium deficiency increases the demand for 25(OH)D above that required in vitamin D deficiency to optimize 1,25(OH)(2)D concentrations. Assessment of vitamin D sufficiency in persons or communities may need to be adjusted for habitual dietary calcium intake.     

Endocrine control and disturbances of calcium and phosphate metabolism in children

Most disorders of extracellular calcium and phosphate metabolism in childhood can be attributed to primary increased or decreased secretion/action of 1,25-dihydroxyvitamin D₃ and parathyroid hormone or primary increased or decreased urinary excretion of phosphate and calcium. Based on this pathogenetic classification the most important diseases related to calcium and phosphate metabolism will be discussed.Abbreviations PTH parathyroid hormone - 1,25(OH)₂D₃ 1,25-dihydroxyvitamin D₃ - 25(OH)D₃ 25-hydroxyvitamin D₃ - 24,25(OH)₂D₃ 24,25-dihydroxyvitamin D₃ - VDR vitamin D deficiency rickets - VDDR vitamin D dependency rickets - MEN multiple endocrine neoplasia - HP hypoparathyroidism - PHP pseudohypoparathyroidism - AHO Albright's hereditary osteodystrophy - XLH X-linked familial hypophosphataemic rickets     

Vitamin D metabolism in biliary atresia: intestinal absorptions of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3

In children with biliary atresia, defective intestinal absorption of vitamin D and impaired hepatic uptake and 25-hydroxylation of vitamin D lead to a deficiency of vitamin D and rickets. We recently observed severe rickets in a 3-year-old boy with corrected biliary atresia resulting in jaundice, despite oral treatment with 1 alpha-hydroxyvitamin D3 (1 alpha-OHD3) or 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. He had low 25-hydroxyvitamin D (25-OHD) and high 1,25-(OH)2D serum levels. Intramuscular vitamin D2 administration produced radiological and biochemical evidence of recovery. Oral 1,25-(OH)2D3 (0.1 microgram/kg) and 25-OHD3 (10 micrograms/kg) tolerance tests were done to assess the ability to absorb vitamin D and the effectiveness of using these drugs orally. Eleven children with corrected biliary atresia, aged 9 months to 7 years, were studied. In oral 1,25-(OH)2D3 tolerance tests, the increments above the baseline serum levels of 1,25-(OH)2D were 140.7 +/- 27.4 pg/ml in nonjaundiced patients (n = 5). In jaundiced patients (n = 3), 1,25-(OH)2D3 absorption in two patients with high basal 1,25-(OH)2D values was lower than that of nonjaundiced patients; however, the absorption in the third patient with a low basal value was similar to that of nonjaundiced patients. In oral 25-OHD3 tolerance tests, the mean increase of serum 25-OHD was 48.9 +/- 30.6 ng/ml in nonjaundiced patients (n = 5) and 23.7 +/- 9.5 ng/ml in jaundiced patients (n = 4), the peak serum 25-OHD levels being reached 6-12 h after 25-OHD3 loading.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of serum osteocalcin as an index of altered bone metabolism

Recent evidence suggests that the protein osteocalcin is like the bone alkaline phosphatase produced by osteoblasts and circulates in human blood. With the introduction of a radioimmunoassay for serum osteocalcin it was hoped that this test would provide a useful index of altered bone metabolism. Therefore serum osteocalcin was measured in 88 controls and 112 patients with disorders of calcium and phosphate metabolism, isolated elevation of alkaline serum phosphatase in the absence of disease (isolated hyperphosphatasaemia) and children prone to osteopenia.In the controls serum osteocalcin was higher in children<15 years (median and range: 11.9, 7.7–15.3 ng/ml) than in adults (3.7, 2.6–5.2 ng/ml) and was highly correlated to alkaline serum phosphatase activity (r=0.87, n=88, P<0.01). Osteocalcin was elevated in primary hypoparathyroidism, low in untreated hypoparathyroidism but normal in hypoparathyroidism (including pseudohypoparathyroidism) during vitamin D treatment. The bone protein was low-normal and increased to high-normal levels during vitamin D therapy in vitamin D deficiency rickets and familial hypophosphataemic rickets, but remained low in patients with end organ resistance to 1,25-dihydroxyvitamin D. Osteocalcin (and urinary hydroxyproline) were not elevated in isolated hyperphosphatasaemia, indicating that mechanisms other than increased bone turnover may account for the markedly elevated serum alkaline phosphatase activity in these subjects. Osteocalcin was decreased in children with diabetes mellitus type I and in patients on glucocorticoid treatment, indicating decreased bone formation. It is concluded that the measurement of serum osteocalcin seems to be a reliable index of bone formation provided that the vitamin D status and renal function are normal. Although serum osteocalcin and alkaline phosphatase were generally correlated there were examples of dissociation between both indices. In some circumstances (e.g. rickets) serum osteocalcin may severe as a useful index of an effective therapy.Abbreviations AP alkaline phosphatase activity - Gla gammacarboxy-glutamic acid - 1,25 (OH)₂D₃ 1,25-dihydroxyvitamin - D₃ calcitriol - PTH parathyroid hormone - HP hypoparathyroidism - PHP pseudohypoparathyroidism - I^oHPT primary hyperparathyroidism - VDR vitamin D deficiency rickets - VDDR II vitamin D dependency rickets type II - FHL familial hypophosphataemic rickets - IH isolated hyperphosphatasaemia in the absence of disease     

VITAMIN D METABOLISM IN HYPOPHOSPHATASIA

ABSTRACT. A 4-month-old boy with the infantile form of hypophosphatasia was followed for 9 months with measurements of serum calcium, phosphate, alkaline phosphatase and various vitamin D metabolites, together with urinary excretion of cyclic AMP. During the initial hypercalcemic stage the serum concentration of 25-hydroxyvitamin D was normal. Urinary cyclic AMP was low and the serum concentration of the dihydroxymetabolites of vitamin D were appropriate to the high serum calcium with low 1,25(OH)₂D and relatively high 24, 25(OH)₂ and 25, 26(OH)₂D levels. Due to restrictions of the vitamin D intake and lack of exposure to sun he developed vitamin D deficiency rickets at 9 months of age with very low serum concentration of 25-hydroxyvitamin D and markedly increased urinary excretion of cyclic AMP. Following vitamin D treatment the serum level of 1,25(OH)₂D showed a brisk rise to a considerably elevated value. Initially the serum concentration of alkaline phosphatase was well below the normal range, rase markedly during the stage of active rickets and returned to the characteristic low levels of hypophosphatasia with healing of the rickets.     

Vitamin D metabolism in hypophosphatasia

A 4-month-old boy with the infantile form of hypophosphatasia was followed for 9 months with measurements of serum calcium, phosphate, alkaline phosphatase and various vitamin D metabolites, together with urinary excretion of cyclic AMP. During the initial hypercalcemic stage the serum concentration of 25-hydroxyvitamin D was normal. Urinary cyclic AMP was low and the serum concentration of the dihydroxymetabolites of vitamin D were appropriate to the high serum calcium with low 1,25-(OH)2D and relatively high 24,25(OH)2D and 25,26(OH)2D levels. Due to restrictions of the vitamin D intake and lack of exposure to sun he developed vitamin D-deficiency rickets at 9 months of age with very low serum concentration of 25-hydroxyvitamin D and markedly increased urinary excretion of cyclic AMP. Following vitamin D treatment the serum level of 1,25(OH)2D showed a brisk rise to a considerably elevated value. Initially the serum concentration of alkaline phosphatase was well below the normal range, rose markedly during the stage of active rickets and returned to the characteristic low levels of hypophosphatasia with healing of the rickets.     

Asymptomatic rickets in adolescent girls

Objective Inadequate sunlight exposure and calcium intake during rapid growth at puberty lead to hypocalcemia, hypovitaminosis D and eventually to overt rickets. To determine serum biochemical findings of rickets in healthy 11–15 yr old girls, the effect of sunlight exposure and oral vitamin D supplementation on serum 25-hydroxy vitamin D and calcium administration in girls with abnormal findings during December 2002 through March 2003 in Tehran, Iran. Methods Healthy middle school girls were selected for estimation of vitamin D, calcium and phosphorus intake by a three-day food recall. And measurement of serum calcium, phosphorus, parathyroid hormone, alkaline-phosphatase and 25-hydroxyvitamin D concentration. The girls with abnormal findings divided in two groups. Hypovitaminosis D girls subdivided into two groups, supplementary sunlight exposure and vitamin-D administrated for them and calcium administration for the second group for 20 days. Results Of 414 girls, the mean daily vitamin D acquirment and calcium intake were 119 ± 52 IU and 360 ± 350 mg among all girls respectively. Mean serum 25-hydroxyvitamin D with two or more abnormal biochemical findings in 15 (3.6%) girls (group I) were 7.8 ng/ml and alkaline phosphatse with normal or low calcium in 29 (7%) girls (group II) was 1187 IU/L. Mean serum calcium was 8.2 mg % in 8 of 29 girls. Serum 25-hydroxyvitamin D before and after sunlight exposure was 7.1 ± 1.9 ng/ml and 13.9 ± 2.4 ng/ml and vitamin D administration was 7.4 ± 1.8 ng/ml (group la) and 27.9 ± 4.2ng/ml (group lb) respectively. Serum alkaline phosphatase before and after calcium administration were 1187 IU/L and 666 IU/L respectively. Conclusion We conclude that low daily calcium intake, and vitamin D acquirement are two important problems in Iranian girls during rapid growth at puberty; therefore, for prevention of overt rickets calcium and vitamin D Supplementation appear to be necessary.     

Serum concentrations of vitamin D metabolites in rachitic Libyan children

Twenty-two consecutive patients with rickets were studied in Benghazi, Libya. All were less than 2 years old. Rickets was associated with traditional cultural habits that limited sunshine exposure of the mothers and their infants, and with breast-feeding. Serum concentrations of the vitamin D metabolites 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D, and other parameters of mineral metabolism were typical of vitamin D deficiency disease, as was the biochemical and clinical response to treatment. Minimum safe serum levels of 25-OHD (20 nmol/L), and the serum levels of vitamin D metabolites in response to vitamin D treatment, were identical to previously obtained results from native Norwegian and Norwegian immigrant children with rickets, suggesting lack of racial differences in response to vitamin D. Fifty percent of the patients had adequate levels of vitamin D metabolites at the time of diagnosis, indicating that they had recently received oral vitamin D or cutaneous exposure to sunshine. Many cases of rickets in the area may, therefore, be spontaneously cured when the children's maturity allows adequate mobility and independence to achieve exposure to sunshine.     

Hypocalcaemia induced by glucocorticoids in a child with hypoparathyroidism treated with 1-α-hydroxyvitamin D3

Glucocorticoids tend to lower the intestinal absorption of calcium, leading to a negative calcium balance. A 7-year-old girl with hypoparathyroidism was maintained as normocalcaemic on 1--hydroxyvitamin D₃ (1D₃) and calcium gluconate lactate. During an episode of aplastic anaemia she was treated with prednisolone, with a subsequent dramatic fall of serum calcium despite 1D₃ treatment and serum 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) in the high-normal range. Glucocorticoids seem to have interfered directly with cellular events reponsible for intestinal absorption of calcium.Abbreviations 1D₃ 1--hydroxyvitamin D₃ - 1,25(OH)₂D₃ 1,25-dihydroxyvitamin D₃ - PTH parathyroid hormone - PTE parathyroid extract - RIA radioimmunoassay - TRP tubular reabsorption of phosphorus     

Treatment of malabsorption vitamin D deficiency myopathy with intramuscular vitamin D

A nearly 5 year-old boy presented with proximal muscle weakness, reduced muscle bulk, a positive Gower sign and Trendelenburg gait. He was known to have cholestatic liver disease. Investigations revealed markedly low serum total calcium, elevated alkaline phosphatase, very low serum 25-hydroxyvitamin D, and radiographs consistent with active rickets despite the ongoing administration of a water-soluble preparation of vitamin D. Only i.v. calcitriol acutely corrected the hypocalcemia, despite trying several oral preparations, suggesting that malabsorption secondary to chronic liver disease was the cause of his rickets. Intramuscular calciferol quickly corrected his muscle weakness and X-ray findings. Myopathy secondary to vitamin D deficiency is an uncommon diagnosis in children. Intermittent calciferol is an inexpensive and practical treatment for vitamin D deficiency, especially if associated with malabsorption.     

Lymphocyte subpopulations in children with vitamin D deficient rickets

Recent studies have shown 1,25(OH)₂D₃-mediated modulation of the immune system. We examined lymphocyte subpopulations of 16 children with nutritional rickets. Most of the patients suffered more frequent infection episodes than the control group of 15 healthy children and low serum levels of 25OHD and 1,25(OH)₂D, such as 38.2 ± 8.6 ng/mL and 15.7 ± 2.6 pg/mL respectively. This decrease correlated with a significant decrease in total T lymphocytes and an increase in B lymphocytes expressing surface IgA, IgM, IgG molecules. These results suggest that vitamin D plays an important role in the impaired functions of T lymphocytes which may lead to frequent infection episodes in nutritional rickets.     

Effect of parathyroid hormone on cAMP and 1,25-dihydroxyvitamin D formation and renal handling of phosphate in vitamin D-dependent rickets

Studies were carried out to compare the effects of parathyroid extract (PTE) on the serum concentration of 1,25-dihydroxyvitamin D (1,25[OH]2D), 24,25-dihydroxyvitamin D (24,25[OH]2D), 25,26-dihydroxy vitamin D (25,26[OH]2D) and cAMP, and the urinary excretion of calcium, phosphorus, and cAMP in two normal adult subjects, and in a girl with vitamin D-dependent rickets. The concentration of 1,25[OH]2D was markedly decreased even when she was receiving a daily dose of 25,000 IU of ergocalciferol. PTE infusion resulted in a prompt and distinct increase in the serum levels and the urinary excretion of cAMP in the patient and control subjects. In the control subjects the serum concentration of 1,25[OH]2D increased after the PTE infusion, whereas there was no response in the patient with vitamin D-dependent rickets. The two other dihydroxylated metabolites of vitamin D showed no consistent response to the PTE infusion in the control subjects or the patient. The patient showed no phosphaturic response to PTE while she was receiving high-dosage ergocalciferol treatment. By contrast, when the patient was re-studied after therapy with 1 alpha-hydroxyvitamin D, PTE infusion resulted in an increase in urinary phosphate excretion. These findings might lend support for the notion that 1,25[OH]2D has an effect on tubular phosphate resorption and has a permissive role in the phosphaturic effect of parathyroid hormone. The present findings also confirm that the formation of 1,25[OH]2D is impaired in vitamin D-dependent rickets and indicate that the renal 25-hydroxyvitamin D-1 alpha-hydroxylase is unresponsive to the stimulatory effect of parathyroid hormone in this condition.     

Unique form of rickets with low serum 25-hydroxyvitamin D in two normally nourished children

We present an unusual type of rickets involving two children: a 2 year old boy and a 15 month old boy, who presented with marked bowing of the lower extremities and bulging of costochondral junctions. Both children had normal growth, with their height and body weight greater than the 50th and 97th percentile for age. Roentgenograms of their extremities showed the typical changes of vitamin D refractory rickets. Serum alkaline phosphatase levels were elevated and serum levels of calcium and phosphate were both within the normal range. No primary cause for the rickets, including nutritional deficiencies, was found in the two patients. Characteristic findings were persistently low serum 25-hydroxyvitamin D (25-OH-D) and normal 1,25-dihydroxyvitamin D (1,25-(OH)2-D). Improvements in clinical and X-ray findings were observed after either oral administration of 1 α-(OH)-D3 (9–15 μg per day) or massive vitamin D2 therapy (600 000 IU single injection). The low serum levels of 25-OH-D did not increase unless massive vitamin D2 therapy was also given. These two cases represent a unique form of rickets that does not meet the criteria for any type of previously known rickets.