Vitamin D deficiency rickets (VDDR) is a disorder biochemically characterized by elevated serum alkaline phosphatase (ALP) activity, normal or decreased serum calcium (Ca) and inorganic phosphate concentrations, secondary hyperparathyroidism and decreased serum 25−hydroxyvitamin D (25(OH)D) levels. In stage 1 VDDR, urinary amino acid and phosphate excretion are normal with minimal or no findings of rickets on radiographs. Pseudohypoparathyroidism (PHP) is an inherited disorder characterized by end−organ resistance to parathormone (PTH). VDDR occasionally resembles PHP type 2 in clinical presentation and biochemical features, creating difficulties in the differential diagnosis of these two entities. Here we report an infant diagnosed with VDDR. In addition to inadequate vitamin D intake, usage of antiepileptic drugs (AED) may have led to the worsening of the vitamin D deficiency. The patient presented with a history of febrile convulsions, for which he received phenobarbital treatment. The initial findings of hypocalcemia, hyperphosphatemia and normal tubular reabsorption of phosphate, mimicking PHP 2, responded well to vitamin D and oral Ca treatment with normalization of serum Ca, phosphorus (P), ALP and PTH levels
Conflict of interest:None declared.
Vitamin D deficiency rickets; Pseudohypoparathyroidism; antiepileptic drugs
Objective: Serum alkaline phosphatase (ALP) levels show great variation with age and sex in children and adolescents. Additionally, different buffers used even in the same method cause variable results. This detail is not usually taken into account in the evaluation. We aimed to study pediatric age- and sex-specific reference ranges for ALP by colorimetric assay using p-nitrophenyl phosphate as substrate and diethanolamine as buffer and also to compare the ALP levels in patients with different types of rickets.
Methods: 1741 healthy children and adolescents (904 girls) were included in the study for normative data. 77 different ALP measurements from 38 nutritional rickets (NR), 7 vitamin D-dependent rickets (VDDR) and 8 hypophosphatemic rickets (HR) patients were included.
Results: Reference values for ALP were constructed. ALP levels demonstrated a tetraphasic course with two peaks at infancy and puberty. There was no difference in ALP levels between boys and girls until puberty. However, higher ALP levels were noted at 10-11 years in girls (p=0.02) and at 12-13, 14-15, 16-17 years in boys (p<0.001). ALP levels start to decline after age 12 and 14 in girls and boys, respectively. Serum ALP levels were highest in the VDDR group and lowest in the HR group (median z-score values in HR, VDDR and NR were 3.6, 10.4 and 6.5, respectively; p<0.001). Similarly, plasma parathormone(PTH) levels ranged from highest to lowest in the VDDR, NR and HR groups (median values: 525, 237 and 98 pg/mL, respectively; p<0.001).
Conclusions: This normative data will provide a basis for better evaluation of ALP levels determined by the described method. Furthermore, use of z-scores gives a more precise assessment of changes in ALP levels in rickets and other bone disorders.
Conflict of interest:None declared.
Alkaline phosphatase; children; reference values; rickets
Rickets is softening of bones due to defective mineralization of cartilage in the epiphyseal growth plate, leading to widening of ends of long bones, growth retardation, and skeletal deformities in children. The predominant cause is deficiency or impaired metabolism of vitamin D. The observation that some forms of rickets could not be cured by regular doses of vitamin D, led to the discovery of rare inherited abnormalities of vitamin D metabolism or vitamin D receptor. Vitamin D dependent rickets (VDDR) is of two types: Type I is due to defective renal tubular 25-hydroxyvitamin D 1-α hydroxylase and type II is due to end-organ resistance to active metabolite of vitamin D. Typical signs are observed from the first month of life. The patient with rickets described below had markedly increased serum alkaline phosphatase and 1,25-dihydroxyvitamin D. We attribute these abnormalities to impaired end-organ responsiveness to 1,25-dihydroxyvitamin D.
End-organ resistance; rickets; vitamin D; vitamin D dependent rickets; 1,25-dihydroxyvitamin D
Objective: Insulin-like growth factor binding protein-4 (IGFBP-4), inhibits IGF actions under a variety of experimental conditions. Parathyroid hormone (PTH), 1.25-hydroxy(OH)vitamin D, IGF-I, IGF-II and transforming growth factor (TGF)-b are the major regulators of IGFBP-4 production in vitro. However, little is known about the in vivo regulation of circulating IGFBP-4 in humans.
Methods: We measured serum concentrations of calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), PTH, vitamin D, IGF-I, IGFBP-3, and IGFBP-4 in infants (n=22) with nutritional rickets before and after treatment of rickets with vitamin D (300 000 U single dose po).
Results: The mean±SD age of the patients was 1.3±1.6 years (range 0.2-3). Serum Ca and P increased, whereas ALP and PTH decreased after treatment (Ca from 6.6±1.4 to 9.5±1.6 mg/dL, P from 3.9±1.4 to 5.4±0.8 mg/dL, ALP from 2590±2630 to 1072±776 IU/mL and PTH from 407±248 to 27.4±20.8 ng/dL, respectively). Vitamin D levels were low (7.8±2.5 ng/mL) and increased after treatment (18.1±4.0 ng/mL, p<0.001). Serum IGF-I and IGFBP-3 levels both increased after treatment (IGF-I: 13.5±12.2 vs. 23.7±14.2 ng/mL, p<0.001 and IGFBP-3: 1108±544 vs. 1652±424 ng/mL, p<0.001). However, serum IGFBP-4 levels did not change significantly after treatment (18.8±8.0 vs. 21.5±4.8 ng/mL). No correlation between PTH and IGF-I, IGFBP-3 or IGFBP-4 was detected. Significant correlations were observed between PTH and ALP (r=0.53, p<0.05), and between IGF-I and IGFBP-3 (r=0.46, p<0.05).
Conclusion: The results demonstrate that contrary to in vivo studies, circulating IGFBP-4 levels are not influenced by secondary hyperparathyroidism in vitamin D deficiency rickets since IGFBP-4 levels did not change after normalization of PTH with vitamin D treatment.
Conflict of interest:None declared.
Vitamin D; rickets; IGF-I; IGFBP-3; IGFBP-4; PTH; Bone
One hundred Asian schoolchildren provided evidence of the relationships between radiological and biochemical evidence of rickets in a vitamin D-deficient population. In a retrospective study of the X-rays of 56 children the variables serum alkaline phosphatase, inorganic phosphorus and age provided a discriminant function which correctly classified 10 of 11 children with radiological evidence of rickets and 44 of 45 children with negative or marginally abnormal X-rays. When the discriminant function was applied to a prospective study of 44 children, three children with radiological evidence of rickets were correctly classified together with 38 of the remaining 41 children with negative or marginally abnormal X-rays. Serum alkaline phosphatase was the most important variable in the discriminant analysis, followed by serum inorganic phosphorus and age. Low levels of serum 25-hydroxy vitamin D (25-OHD) are of little value in predicting the severity of radiological evidence of rachitic bone disease in a vitamin D-deficient population.
Serum levels of calcium, phosphorus, alkaline phosphatase, and 25 hydroxy-vitamin D (25-OH-D3) were measured in normal and malnourished children with and without rickets. Children with rickets had clinical, biochemical, and x-ray evidence of the disease; most of them were malnourished. 25-OH-D3 levels were lower than in normal children. After treatment with vitamin D their condition improved. 25-OH-D3 levels were also found to be reduced in malnourished children without rickets. These studies show that rickets is common in malnourished children. Inadequate exposure to sunlight appears to be the factor mainly responsible for the high incidence of the disease. In addition, malnutrition perhaps contributes to the development of rickets.
Among 569 schoolchildren (386 boys and 183 girls) aged 14-17 years, 233 had serum alkaline phosphatase values of 30 K.A. units or greater. There was no significant difference in the results in Asian, white, or West Indian children. The mean values were significantly greater in boys than girls and both showed a fall in mean values with increasing age. Radiological rickets occurred in at least 4% of the survey, and was more common in Asians. Low calcium and high hydroxyproline excretion in most of those investigated and the response to vitamin D therapy suggests that most children with alkaline phosphatase levels above 30 K.A. units have rickets.
Since the decline of the widespread supplementation of the diet with vitamin D, the demands of the physiological growth spurt for extra vitamin D in adolescents already on a borderline intake may be responsible for the great increase in “biochemical” rickets. Once the growth spurt is over the condition subsides but the results of impaired growth or permanent pelvic deformity will not necessarily be eradicated.
A 12-week-old domestic cat presented at a local veterinary clinic with hypocalcemia and skeletal abnormalities suggestive of rickets. Osteomalacia (rickets) is a disease caused by impaired bone mineralization leading to an increased prevalence of fractures and deformity. Described in a variety of species, rickets is most commonly caused by vitamin D or calcium deficiencies owing to both environmental and or genetic abnormalities. Vitamin D-dependent rickets type 1A (VDDR-1A) is a result of the enzymatic pathway defect caused by mutations in the 25-hydroxyvitamin D3-1-alpha-hydroxylase gene [cytochrome P27 B1 (CYP27B1)]. Calcitriol, the active form of vitamin D3, regulates calcium homeostasis, which requires sufficient dietary calcium availability and correct hormonal function for proper bone growth and maintenance. Patient calcitriol concentrations were low while calcidiol levels were normal suggestive of VDDR-1A. The entire DNA coding sequencing of CYP27B1 was evaluated. The affected cat was wild type for previously identified VDDR-1A causative mutations. However, six novel mutations were identified, one of which was a nonsense mutation at G637T in exon 4. The exon 4 G637T nonsense mutation results in a premature protein truncation, changing a glutamic acid to a stop codon, E213X, likely causing the clinical presentation of rickets. The previously documented genetic mutation resulting in feline VDDR-1A rickets, as well as the case presented in this research, result from novel exon 4 CYP27B1 mutations, thus exon 4 should be the initial focus of future sequencing efforts.
Objective: To investigate the frequency and effects of vitamin D deficiency in children with type 1 diabetes (T1D) in a region which is known to have a high rate of vitamin D deficiency among adolescents.
Methods: In this prospective cross-sectional study, 120 children and adolescents with T1D (55 girls and 65 boys) aged 3-20 years were evaluated. Serum 25-hydroxyvitamin D [25(OH)D], parathormone (PTH), and alkaline phosphatase (ALP) levels were measured. Hemoglobin A1c levels and daily insulin requirement were also evaluated. Classification of vitamin D status was made according to the American Academy of Pediatrics (AAP)/LWEPS’s recommendations. The patients were divided into 2 groups according to their vitamin D status and also according to the season of the year in which 25(OH)D sampling was done.
Results: Serum 25(OH)D levels revealed vitamin D deficiency or insufficiency in 38% of the patients. Higher PTH levels were found in the patient group whose mean 25(OH)D level was <20 ng/mL as compared to the group whose mean 25(OH)D level was >20 ng/mL (p<0.05). Only 11% of patients had secondary hyperparathyroidism. The 25(OH)D levels of patients whose serum samples were taken in summer and spring months were significantly different (p<0.05). There were no significant correlationsbetween 25(OH)D level and daily insulin dose.
Conclusion: Although we could not show a significant association between vitamin D deficiency and metabolic parameters, the frequency of vitamin D deficiency in T1D children is substantial. Vitamin D status should be assessed also in patients who do not have signs of rickets.
Conflict of interest:None declared.
Vitamin D; type 1 diabetes; children and adolescents
Rickets/osteomalacia is an important problem in a tropical country. Many cases are due to poor vitamin D intake or calcium deficient diets and can be corrected by administration of calcium and vitamin D. However, some cases are refractory to vitamin D therapy and are related to renal defects. These include rickets of renal tubular acidosis (RTA), hypophosphatemic rickets, and vitamin D dependent rickets (VDDR). The latter is due to impaired action of 1α-hydroxylase in renal tubule. These varieties need proper diagnosis and specific treatment.
Hypophosphatemic rickets; osteomalacia; renal rickets; rickets; renal tubular acidosis; vitamin D rickets
Calciferol therapy for 12 months in white, Asian, and West Indian schoolchildren resulted in a highly significant increase in height and weight when compared with schoolchildren not so treated. The rate of fall of serum alkaline phosphatase was similar in both the treated and untreated schoolchildren and in other children treated in hospital for rickets. Dietary studies on 9% of the total survey by weighed inventory methods showed a low average intake of vitamin D, while random estimates of 25-hydroxycalciferol levels on 6% of the children were less than 3·8 ng/ml in 40% of those studied (principally Asian). It was concluded that there was a significant problem of vitamin D deficiency among Asian and West Indian teenagers and that white children were also affected to a less degree.
The epidemic scourge of rickets in the 19th century was caused by vitamin D deficiency due to inadequate sun exposure and resulted in growth retardation, muscle weakness, skeletal deformities, hypocalcemia, tetany, and seizures. The encouragement of sensible sun exposure and the fortification of milk with vitamin D resulted in almost complete eradication of the disease. Vitamin D (where D represents D2 or D3) is biologically inert and metabolized in the liver to 25-hydroxyvitamin D [25(OH)D], the major circulating form of vitamin D that is used to determine vitamin D status. 25(OH)D is activated in the kidneys to 1,25-dihydroxyvitamin D [1,25(OH)2D], which regulates calcium, phosphorus, and bone metabolism. Vitamin D deficiency has again become an epidemic in children, and rickets has become a global health issue. In addition to vitamin D deficiency, calcium deficiency and acquired and inherited disorders of vitamin D, calcium, and phosphorus metabolism cause rickets. This review summarizes the role of vitamin D in the prevention of rickets and its importance in the overall health and welfare of infants and children.
44 randomly selected infants under age one year with suspected lower respiratory infections were investigated for the presence of subclinical rickets. Seven infants had metaphyseal changes at the wrist compatible with a diagnosis of rickets and all of these infants had 25-hydroxy-vitamin D (25-OHD) concentrations less than 12 ng/ml. Serum calcium and phosphorus concentrations were normal in all 44 children. Alkaline phosphatase concentrations did not correlate with the presence of metaphyseal changes. The clinical presence of craniotabes or splaying and loss of definition of the anterior ends of the ribs on x-rays did not correlate with metaphyseal changes at the wrist or with 25-OHD concentrations. An x-ray of the wrist is essential to confirm the presence of subclinical rickets and the at-risk infant can be detected by measuring serum 25-OHD concentrations.
Children with calcium-deficiency rickets may have increased vitamin D requirements and respond differently to vitamin D2 and vitamin D3. Our objective was to compare the metabolism of vitamins D2 and D3 in rachitic and control children. We administered an oral single dose of vitamin D2 or D3 of 1.25 mg to 49 Nigerian children—28 with active rickets and 21 healthy controls. The primary outcome measure was the incremental change in vitamin D metabolites. Baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations ranged from 7 to 24 and 15 to 34 ng/mL in rachitic and control children, respectively (p < .001), whereas baseline 1,25-dihydroxyvitamin D [1,25(OH)2D] values (mean ± SD) were 224 ± 72 and 121 ± 34 pg/mL, respectively (p < .001), and baseline 24,25-dihydroxyvitamin D [24,25(OH)2D] values were 1.13 ± 0.59 and 4.03 ± 1.33 ng/mL, respectively (p < .001). The peak increment in 25(OH)D was on day 3 and was similar with vitamins D2 and D3 in children with rickets (29 ± 17 and 25 ± 11 ng/mL, respectively) and in control children (33 ± 13 and 31 ± 16 ng/mL, respectively). 1,25(OH)2D rose significantly (p < .001) and similarly (p = .18) on day 3 by 166 ± 80 and 209 ± 83 pg/mL after vitamin D2 and D3 administration, respectively, in children with rickets. By contrast, control children had no significant increase in 1,25(OH)2D (19 ± 28 and 16 ± 38 pg/mL after vitamin D2 and D3 administration, respectively). We conclude that in the short term, vitamins D2 and D3 similarly increase serum 25(OH)D concentrations in rachitic and healthy children. A marked increase in 1,25(OH)2D in response to vitamin D distinguishes children with putative dietary calcium-deficiency rickets from healthy children, consistent with increased vitamin D requirements in children with calcium-deficiency rickets. © 2010 American Society for Bone and Mineral Research.
metabolic bone; vitamin D; calcium; pediatric; nutrition
Vitamin-D-deficient rickets still exists in children in Manitoba and adjacent areas. Between 1972 and 1984, 48 cases were documented at Winnipeg Children's Hospital. The patients ranged in age from 1 to 49 months; 40 were Canadian natives (38 Indians and 2 Inuit), most of whom lived in the Island Lake area of northern Manitoba. Of the 48, 16 had clinical signs of rickets, 12 had tetany due to hypocalcemia and 38 had radiologic evidence of rickets. Hypocalcemia was found in 27, and hypophosphatemia in 19; hyperaminoaciduria was found in 7 of 20. All 48 had elevated serum alkaline phosphatase levels. In addition to rickets, 16 patients aged 12 months or more had evidence of malnutrition. Climate and lifestyle in northern areas of the Canadian midwest result in little or no biosynthesis of vitamin D by solar radiation; therefore, adequate dietary vitamin D intake is essential to prevent deficiency. The diets of pregnant women and infants in these areas are deficient in vitamin D. The authors recommend vitamin D supplements for all pregnant women and infants in areas of risk to eradicate this preventable disease.
Twenty-seven unselected patients were investigated three to eight years after jejunoileal bypass for morbid obesity. The serum levels of calcium, magnesium, and phosphorus, and the renal excretions of calcium and magnesium were reduced. The serum alkaline phosphatase levels were increased. The serum levels of the two vitamin D metabolites 25-hydroxyvitamin D (25-OHD) and 1.25-dihydroxyvitamin D (1.25-(OHD)2D) were reduced and inversely related to the increased serum levels of immunoreactive parathyroid hormones (iPTH). Serum 1.25-(OH)2D correlated positively and serum iPTH inversely with serum concentrations and renal excretion rates of calcium. Iliac crest bone biopsies after in vivo tetracycline double-labelling showed a reduced bone turnover with an increased amount of osteoid due to an increase in both surface extent and mean width of osteoid seams. The increased volume of osteoid was caused by a decreased osteoblastic function with a longer life-span of bone-forming sites and a prolongation of the mineralisation lag time. The amount of trabecular bone was normal. The results indicate an impaired vitamin D metabolism with osteomalacia and secondary hyperparathyroidism.
Objective. This study describes the magnitude and characteristics of nutritional rickets and associated risk factors among children in Qatar. Subjects. A consecutive sample of 730 healthy subjects who visited the primay health care clinics were approached and 540 (73.9%) subjects gave consent. Mehods. Nutritional rickets diagnosis was based on clinical radiologic and biochemical parameters and normalization of alkaline phosphatase level after 6 weeks course of daily vitamin D therapy. Results. The study revealed that 23.9% of the studied children had nutritional rickets. The mean ± SD age of those with rickets (3.76 years ± 1.51) was slightly higher than those without rickets (3.57 years ± 1.45). Family history of vitamin D deficiency (44.2%; P = .001) and diabetes mellitus (53.5%; P = .002) were significantly higher in rachitic children than in nonrachitic children. The children with rickets spent a significantly shorter average duration (26.86 minutes ± 19.94) under the sun than those without rickets (30.59 minutes ± 15.72; P < .001). A significantly larger proportion of rachitic children was afflicted with vitamin D deficiency (75.2% versus 62.2%; P < .001), secondary hypothyroidism (100% versus 7.5%; P = .009) and muscular weakness (56.6% versus 26.3%; P < .001). Conclusion. The most important risk factors were low vitamin D and calcium intakes, lack of exposure to sunlight, prolonged breast feeding without supplementation of vitamin D.
Eight Pakistani children with late rickets and two Pakistani women with osteomalacia were given a chupatty-free diet for seven weeks, substituting leavened bread of lower extraction. On this diet serum calcium levels rose to normal or near normal, levels of serum inorganic phosphorus rose slightly but significantly, and serum alkaline phosphatase levels showed a definite rise indicative of healing bone disease. It is concluded that the high phytate content of unleavened bread is the major cause of late rickets and osteomalacia in Pakistani and Indian communities in the United Kingdom. The simplest prophylactic measure seems to be the additional fortification with calcium carbonate of the high extraction flour used in preparing unleavened bread.
In an oral calcium-loading test performed on 10 infants with vitamin-D deficiency rickets and low fasting calcium levels, a comparison of results before and after therapy showed that vitamin D raised the serum calcium level at each stage of the test and altered the response so that a more rapid and substantial rise and fall in serum calcium occurred.
The effects of vitamin D therapy on newborn infants with hypocalcaemic hyperphosphataemic tetany in another study suggests that these infants should be treated in this way to make them more responsive to oral calcium therapy.
An epidemiological study on vitamin D-dependent rickets was carried out in severely handicapped institutionalised children on long-term anticonvulsant therapy. Nine (10%) of 94 patients had overt rickets on the basis of roentgenological bone changes and biochemical indices, but 46 patients in hospital without medication, and 50 epileptic patients attending an outpatient clinic and taking anticonvulsants had no sign of rickets. Causative factors for the development of rickets were evaluated. Administration of anticonvulsive drugs depressed the serum 25-hydroxyvitamin D (25-OHD) level, but this was not the major factor in the development of rickets. Vitamin D intake seemed to be about average in these patients and its supplementation increased their serum 25-OHD level. This serum 25-OHD level was not maintained by supplemental vitamin D, unless the children were exposed to sunlight. These results indicate that although several factors--such as anticonvulsants, low vitamin D intake, and inactivity--are concerned in the development of rickets, the main cause is lack of sun in institutionalised handicapped children.
Aim: To determine the prevalence of vitamin D hypovitaminosis among obese and overweight schoolchildren.
Design: A cross−sectional population based sample.
Methods: In a cross−sectional study, 301 students (177 girls and 124 boys) aged 11−19 years were selected by multistage stratified sampling design. Subjects were classified according to their body mass index as obese, overweight and normal. Serum 25−hydroxyvitamin D (25−OHD), intact parathyroid hormone (iPTH) and alkaline phosphatase (ALP) were measured in late winter months. Vitamin D deficiency was defined as a 25−OHD 20 ng/ml.
Results: The prevalence of hypovitaminosis D was found as 65% in all students. Vitamin D deficiency was found in 12% and insufficiency in 53% of all students. Vitamin D deficiency in female students was about two times more common than in males. In obese and overweight schoolchildren with hypovitaminosis D, serum 25−OHD levels decreased as BMI increased. There were no correlations between serum 25−OHD and ALP and iPTH levels.
Conclusion: Vitamin D deficiency and insufficiency are common in obese and overweight schoolchildren, especially in girls. Obesity could be a risk factor in terms of hypovitaminosis D in adolescents. Vitamin D supplementation should be administered particularly to adolescent girls.
Conflict of interest:None declared.
adolescents; obesity; Vitamin D; hypovitaminosis D; schoolchildren
Hypophosphatemic rickets is an uncommon metabolic bone disorder which affects all ages and both sexes. It is characterized by low concentration of serum phosphate levels, impairment of mineralization of bone matrix and teeth with variable etiology. Dental problems in this disorder have not been described well in previous studies.
All hypophosphatemic rickets patients who came to a referral clinic during 2008-2010 enrolled in this study. All patients had low phosphorous and high ALP, normal PTH and 25-hydroxy-vitamin D and normal or low level of serum calcium. After diagnosis all patients were examined by a dentist for enamel hypoplasia, taurodontism, dental abscess, gingivitis, dental caries, and dentition delay.
Nineteen patients were enrolled in this study. The average age of the patients was 10 (±4.23) years (range 3-17). Seventy-nine percent of patients had regular follow-up after diagnosis of background disease. Dental caries and delay in the dentition were most prevalent (each one 47.7%) followed by enamel hypoplasia in 42.1% of the patients. Other problems were taurodontism in 15.8% patients, dental abscess and gingivitis in 10.9%.
Hypophosphatemic rickets is a disease with different clinical features; one of them is dental problem, dental caries is the most common problem.
Dental caries; Hypophosphatemia; Rickets; Enamel hypoplasia
We report the beneficial effects of calcium infusions in a child with hereditary resistance to 1,25(OH)2D and alopecia. This patient after transient responsiveness to vitamin D derivatives became unresponsive to all therapy despite serum 1,25(OH)2D concentrations maintained at levels approximately 100-fold normal. A 7-mo trial with calcium infusions led to correction of biochemical abnormalities and healing of rickets. Bone biopsies (n = 3) showed a normal mineralization and the disappearance of the osteomalacia. Cultures of bone-derived cells demonstrated a lack of activation of 25-hydroxyvitamin D 24-hydroxylase and osteocalcin synthesis by 1,25(OH)2D3 (10(-9) and 10(-6) M). These results demonstrate that even in the absence of a normal 1,25(OH)2D3 receptor-effector system in bone cells, normal mineralization can be achieved in humans if adequate serum calcium and phosphorus concentrations are maintained; and calcium infusions may be an efficient alternative for the management of patients with this condition who are unresponsive to large doses of vitamin D derivatives.
Elevated serum alkaline phosphatase (ALP) is a screening marker for the diagnosis of vitamin D deficiency, which may fail to be diagnosed if serum ALP is not elevated. Here, we describe a case of vitamin D deficiency without elevation of serum ALP. A 1-year-old Japanese girl was referred to our hospital for the evaluation of genu varum. Her serum intact PTH level was elevated, while her serum ALP level was normal. Furthermore, her serum 25-hydroxyvitamin D level was reduced, and her urine phosphoethanolamine (PEA) level was mildly elevated. ALPL gene analysis revealed she was a heterozygous carrier of hypophosphatasia (c.1559delT). Serum intact PTH and urine PEA evaluations were helpful for diagnosing vitamin D deficiency and hypophosphatasia carrier status, respectively. Therefore, the possibility of vitamin D deficiency without elevation of serum ALP should be considered.
vitamin D deficiency; hypophosphatasia; ALPL; intact PTH; phosphoethanolamine
Thirty patients with thalassemia major receiving repeated blood transfusion were studied to see their serum parathyroid hormone (PTH) and calcium status. Serum PTH, serum and 24 h urinary calcium, and serum alkaline phosphatase, phosphorus, and albumin-corrected calcium levels were determined. Half of these patients, in addition to transfusion, were also supplemented with vitamin D (60,000 IU for 10d) and calcium (1500 mg/day for 3 months). Serum PTH, and serum and 24 h urinary calcium concentrations of the patients receiving transfusions were found to be significantly reduced while their serum alkaline phosphatase, phosphorus, and albumin-corrected calcium levels were not significantly altered when compared to the respective mean values for the control group. Vitamin D and calcium supplementation significantly increased their serum PTH and calcium levels. Supplementations also increased urinary excretion of calcium. The results thus suggest that patients with thalassemia have hypoparathyroidism and reduced serum calcium concentrations that in turn were improved with vitamin D and calcium supplementation.
Parathyroid hormone; Calcium; Thalassemia