RESUMO
UNLABELLED: Adding to the debate around vitamin D's effects on skeletal health, we report the long-term follow-up of two patients with severe vitamin D receptor mutations, who had normal bone mass acquisition and normalization of calcemia around puberty, suggesting that vitamin D might not be essential for skeletal health in adulthood. INTRODUCTION: Vitamin D plays a pivotal role in calcium homeostasis, and the consequences of vitamin D insufficiency for skeletal health, as well as the importance of its supplementation, are a matter of great interest. Individuals bearing homozygous vitamin D receptor (VDR) defects present with severe hypocalcemic rickets in early infancy due to vitamin D resistance. METHODS: Here, we report the follow-up of two patients with hereditary vitamin D-resistant rickets (HVDRR), focusing on bone mass acquisition and evolution of calcemia. RESULTS: Patient 1 is a 30-year-old male bearing a homozygous p.Arg30* nonsense mutation in the VDR DNA-binding domain, who presented at 6 months. From 9 years of age, treatment requirement decreased progressively. Follow-up with DXA showed normal bone mass acquisition. In adulthood, he maintains normocalcemia without calcium supplementation and has no signs of bone fragility. Patient 2 is a 37-year-old female with milder HVDRR and alopecia due to a homozygous p.Gly319Val mutation in the VDR ligand-binding domain. Around puberty, hypercalciuria and kidney stones were detected, resulting in suspension of treatment. Follow-up with DXA revealed normal bone mass, and she maintained normocalcemia without supplementation during gestation and lactation. CONCLUSIONS: The long-term follow-up of HVDRR provides insights into the role of vitamin D in human calcium homeostasis and bone health. The normalization of calcemia and normal bone mass acquisition despite a permanently dysfunctional VDR suggest that vitamin D might not be essential for skeletal health in adulthood. Extrapolation of these findings may have implications in broader clinical settings, especially considering widespread vitamin D supplementation.
Assuntos
Densidade Óssea/genética , Hipercalcemia/genética , Mutação , Receptores de Calcitriol/genética , Adulto , Cálcio/sangue , Feminino , Seguimentos , Humanos , Hipercalcemia/sangue , Masculino , Linhagem , Raquitismo/sangue , Raquitismo/genéticaRESUMO
AIM: Hypocalcaemia evaluation of the clinical, biochemical and radiologicalfeatures of 91 infants with rickets who presented as hypocalcaemic convulsions. SUBJECTS AND METHODS: Ninety-one hypocalcaemic infants who were brought to hospital with convulsion and diag-nosed with rickets related to vitamin D deficiency according to their clinical, biochemical and radio-logicalfeatures were retrospectively reviewed. RESULTS: Mean values of the laboratory data were as follows: calcium 5.55 +/- 0.79 mg/dL, phosphorus 4.77 +/- 1.66 mg/dL, alkaline phosphatase 1525.5 +/- 925.4 U/L and parathormone 256.8 +/- 158.3 pg/mL. Serum 25-OH vitamin D levels were below normal (< 20 ng/mL) in 37 infants. CONCLUSION: Vitamin D deficiency should be considered in infants presenting with hypocalcaemia. To avoid complications such as convulsions, clinicians should give vitamin D supplementation to such infants.
Assuntos
Hipocalcemia/etiologia , Raquitismo/complicações , Convulsões/etiologia , Fosfatase Alcalina/sangue , Cálcio/sangue , Pré-Escolar , Feminino , Humanos , Hipocalcemia/sangue , Lactente , Recém-Nascido , Masculino , Hormônio Paratireóideo/sangue , Fósforo/sangue , Estudos Retrospectivos , Raquitismo/sangue , Convulsões/sangue , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicaçõesAssuntos
Raquitismo/etiologia , Calcifediol/sangue , Feminino , Humanos , Lactente , Recém-Nascido , Mães , Nigéria , Raquitismo/sangueRESUMO
OBJECTIVE: To determine the prevalence of vitamin D deficiency in young Nigerian children residing in an area where nutritional rickets is common. STUDY DESIGN: A randomized cluster sample of children aged 6 to 35 months in Jos, Nigeria. RESULTS: Of 218 children evaluated, no child in the study had a 25-hydroxyvitamin D (25-OHD) concentration <10 ng/mL (the generally held definition of vitamin D deficiency). Children spent an average of 8.3 hours per day outside of the home. Twenty children (9.2%) had clinical findings of rickets. Children with clinical signs of rickets were more likely to be not currently breast fed and have significantly lower serum calcium concentrations than those without signs of rickets (9.1 vs 9.4 mg/dL, respectively, P =.01). Yet, 25-OHD levels were not significantly different between those children with clinical signs of rickets and those without such clinical signs. CONCLUSION: Vitamin D deficiency was not found in this population of young children in whom clinical rickets is common. This is consistent with the hypothesis that dietary calcium insufficiency, without preexisting vitamin D deficiency, accounts for the development of clinical rickets in Nigerian children.
PIP: Deficiencies of either calcium or vitamin D can cause nutritional rickets. Findings are reported from a study conducted to assess the prevalence of vitamin D deficiency in young Nigerian children living in an area where nutritional rickets is common. A random sample of 218 children aged 6-35 months in Jos, Nigeria, was evaluated. The children were of mean age 22 months. No child had a 25-hydroxyvitamin D (25-OHD) concentration of less than 10 ng/ml, the generally held definition of vitamin D deficiency. Children spent an average of 8.3 hours/day outside of the home, and 20 children (9.2%) had clinical findings of rickets. Children with clinical signs of rickets were more likely to be not currently breast-fed and have significantly lower serum calcium concentrations than those with no signs of rickets. 25-OHD levels were not significantly different between children with clinical signs of rickets and those without such clinical signs. The failure to find vitamin D deficiency in this population of young children in whom clinical rickets is common is consistent with the hypothesis that dietary calcium insufficiency, without preexisting vitamin D deficiency, accounts for the development of rickets in Nigerian children.
Assuntos
Cálcio/deficiência , Raquitismo/etiologia , Deficiência de Vitamina D/epidemiologia , Aleitamento Materno , Cálcio/sangue , Cálcio da Dieta/administração & dosagem , Pré-Escolar , Análise por Conglomerados , Estudos Transversais , Deficiências Nutricionais/complicações , Deficiências Nutricionais/diagnóstico , Deficiências Nutricionais/epidemiologia , Feminino , Humanos , Lactente , Masculino , Nigéria/epidemiologia , Prevalência , Raquitismo/sangue , Deficiência de Vitamina D/complicaçõesRESUMO
We studied 26 Nigerian children with active rickets (13 boys, 13 girls), aged 1 to 5 years, and compared results of biochemical studies with those of healthy control subjects. The plasma 1,25-dihydroxyvitamin D level was elevated (568 +/- 317 pmol/L) and the 25-hydroxyvitamin D level was (36 +/- 28 mol/L) in the children with rickets compared with the control subjects (369 +/- 134 nmol/L and 69 +/- 22 nmol/L, respectively). The results suggest that rickets in Nigeria is largely the result of calcium deficiency and that vitamin D deficiency and possibly end organ resistance may be contributory factors.
Assuntos
Cálcio/deficiência , Raquitismo/etiologia , Deficiência de Vitamina D/complicações , Cálcio/sangue , Estudos de Casos e Controles , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Nigéria/epidemiologia , Raquitismo/sangue , Raquitismo/epidemiologia , Deficiência de Vitamina D/sangueRESUMO
Vitamin D dependent rickets type II is an autosomal recessive disease caused by the vitamin D defective receptor. More than 200 patients with different types of lower limb deformities were detected in a rural area of the Cauca department in the southwest part of Colombia. Patients were well nourished and in good physical condition in spite of their deformities. None of them presented alopecia, myopathy, seizures or aminoaciduria. Serum analysis showed significantly lower serum calcium as compared to normal relatives, though in the normal low range, normal phosphorus, high alkaline phosphatase, normal 25-hydroxyvitamin D3 and high 1,25-dihydroxyvitamin D3, indicating target organ resistance. The cDNA analysis showed normal nucleotide sequence. We suggest that our patients represent a distinct form of receptor-positive resistance to vitamin D. This report is the first extensive study on this class of patients.
Assuntos
Receptores de Calcitriol/genética , Raquitismo/genética , Adulto , Criança , Colômbia , Feminino , Humanos , Masculino , Reação em Cadeia da Polimerase , Raquitismo/sangue , Raquitismo/urina , Vitamina D/análiseRESUMO
A single-day large dose of vitamin D (stosstherapy) was given to 42 patients with nutritional vitamin D-deficiency rickets. Stosstherapy is safe and effective, obviates problems with compliance, and, by evoking a response in 4 to 7 days in nutritional rickets, becomes a valuable diagnostic aid for patients in whom initial findings do not clearly distinguish nutritional rickets from familial hypophosphatemic rickets.
Assuntos
Raquitismo/tratamento farmacológico , Deficiência de Vitamina D/tratamento farmacológico , Vitamina D/uso terapêutico , Administração Oral , Cálcio/administração & dosagem , Cálcio/sangue , Cálcio/uso terapêutico , Cápsulas , Criança , Pré-Escolar , Esquema de Medicação , Ergocalciferóis/administração & dosagem , Ergocalciferóis/uso terapêutico , Humanos , Hiperparatireoidismo Secundário/etiologia , Hipocalcemia/etiologia , Hipofosfatemia Familiar/diagnóstico , Hipofosfatemia Familiar/tratamento farmacológico , Lactente , Fosfatos/sangue , Raquitismo/sangue , Raquitismo/complicações , Vitamina D/administração & dosagem , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicaçõesRESUMO
The cause of the growth retardation present in patients with hypophosphatemic rickets has not been totally elucidated. There has been a previous report of a growth hormone deficit in a group of these patients. To verify this abnormality we studied two groups of patients with hypophosphatemic rickets, one with (n = 6) and the other without (n = 7) treatment with calcitriol and oral phosphates. All patients in both groups showed a normal growth hormone response (> 10 micrograms/l) to standard stimulatory tests and normal IGF-I plasma levels. Mean IGF-I plasma levels were not significantly different (untreated 1.46 +/- 0.80 U/ml, treated 1.25 +/- 0.69 U/ml) and the mean logarithmic deviation of IGF-I plasma levels from both groups did not differ from normal. In summary, we found no abnormalities of the growth hormone-IGF-I axis in our patients with hypophosphatemic rickets.
Assuntos
Hormônio do Crescimento/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Fosfatos/sangue , Raquitismo/sangue , Absorção , Adolescente , Determinação da Idade pelo Esqueleto , Cálcio/sangue , Criança , Pré-Escolar , Humanos , Túbulos Renais/metabolismo , Fosfatos/metabolismoRESUMO
This paper describes a 9-year-old girl with primary hypophosphatemic rickets, an uncommon cause of bowed legs. A simple screening for patients presenting with bowed legs is suggested and the importance of using age-related standards for comparison of biochemical results is emphasized.
Assuntos
Fosfatos/sangue , Raquitismo/diagnóstico , Criança , Feminino , Humanos , Raquitismo/sangue , Raquitismo/etiologiaRESUMO
Para analizar la mayor incidencia de raquitismo nutricional en el Sur de la Argentina, se estudiaron durante el mes de agosto niños clínicamente sanos de edad promedio siete años de Buenos Aires (n = 37) y de Ushuaia (n = 63). Se midieron niveles séricos de calcio, fósforo, fosfatasa alcalina y 25-OH-D. Además, se determinaron los niveles de este metabolito en un grupo de 29 niños de Buenos Aire de edad promedio 13 años. Los valores de 25-OH-D fueron significativamente menores (p < 0.001) en Ushuaia: (xñ1ES)9.3ñ0.64ng/ml que en los dos grupos etarios de Buenos Aires: 21.1 ñ 2.03 ng/ml y 19.0ñ1.18ng/ml. No hubo diferencias entrre los niveles de calcemia y fosfatasemia alcalina. La fosfatemia fue mayor en los niños de Ushuaia. La ingesta cálcica que fue mayor en Ushuaia se correlacionó positivamente en esta zona con los niveles de 25-OH-D. En síntesis, los niños sanos de Ushuaia tienen niveles de 25-OH-D disminuidos al final del invierno, debido probablemente al menor número de horas de sol disponible y a una menor radiación ultravioleta efectiva para la síntesis en piel de vitamina D
Assuntos
Humanos , Pré-Escolar , Criança , Adolescente , Masculino , Feminino , 25-Hidroxivitamina D 2/sangue , Raquitismo/sangue , Fosfatase Alcalina/sangue , Argentina , Cálcio/sangue , Valores de Referência , Estações do AnoRESUMO
Para analizar la mayor incidencia de raquitismo nutricional en el Sur de la Argentina, se estudiaron durante el mes de agosto niños clínicamente sanos de edad promedio siete años de Buenos Aires (n = 37) y de Ushuaia (n = 63). Se midieron niveles séricos de calcio, fósforo, fosfatasa alcalina y 25-OH-D. Además, se determinaron los niveles de este metabolito en un grupo de 29 niños de Buenos Aire de edad promedio 13 años. Los valores de 25-OH-D fueron significativamente menores (p < 0.001) en Ushuaia: (xñ1ES)9.3ñ0.64ng/ml que en los dos grupos etarios de Buenos Aires: 21.1 ñ 2.03 ng/ml y 19.0ñ1.18ng/ml. No hubo diferencias entrre los niveles de calcemia y fosfatasemia alcalina. La fosfatemia fue mayor en los niños de Ushuaia. La ingesta cálcica que fue mayor en Ushuaia se correlacionó positivamente en esta zona con los niveles de 25-OH-D. En síntesis, los niños sanos de Ushuaia tienen niveles de 25-OH-D disminuidos al final del invierno, debido probablemente al menor número de horas de sol disponible y a una menor radiación ultravioleta efectiva para la síntesis en piel de vitamina D (AU)
Assuntos
Humanos , Pré-Escolar , Criança , Adolescente , Masculino , Feminino , Raquitismo/sangue , 25-Hidroxivitamina D 2/sangue , Estações do Ano , Valores de Referência , Cálcio/sangue , Fosfatase Alcalina/sangue , ArgentinaRESUMO
Public Health Annals recording diagnosis of nutritional rickets in patients admitted in Public Hospitals disclosed that from birth to age 14, in the period 1980-1981, the incidence was 2.7 higher in the Patagonia (latitude 39 degrees S to 55 degrees S) compared with the Pampeana Region and 8.5 higher than in the rest of the country. After informed parental consent 37 healthy children of Buenos Aires (34 degrees S) with an age of (Av +/- 1 SD) 7.0 +/- 1.2 years, 29 with an age of 13.1 +/- 1.5 years and 63 of Ushuaia (55 degrees S) with an age of 7.1 +/- 0.8 years were studied at the end of winter (August). Serum levels of 25-OH-D were as follows (mean +/- SE): Buenos Aires: 21.1 +/- 2.03 ng/ml (Average: seven years old), 19.0 +/- 1.18 ng/ml (children of thirteen years old) and Ushuaia: 9.3 +/- 0.64 ng/ml (p less than 0.001) (Fig. 2). Serum levels were below 8 ng/ml in 52% of the children in Ushuaia but only in 9% in Buenos Aires. Serum calcium and alkaline phosphatase levels were similar in the two groups but serum phosphate was higher in Ushuaia (Table 1). The calcium intake was greater in Ushuaia (811 +/- 49 mg/day) than in Buenos Aires (634 +/- 61 mg/day) and was correlated with 25-OH-D levels in children of Ushuaia (r = 0.50, p less than 0.001) but not in Buenos Aires (r = 0.08). The main source of calcium intake was vitamin D fortified milk. These results disclosed a significantly diminished level of serum 25-OH-D in Ushuaia.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
25-Hidroxivitamina D 2/sangue , Raquitismo/sangue , Adolescente , Fosfatase Alcalina/sangue , Argentina , Cálcio/sangue , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estações do AnoRESUMO
Seventy-one very low birth weight (less than or equal to 1500 gm) infants were studied to determine the sequential changes in serum vitamin D metabolite concentrations between infants with and without radiographically documented rickets, fractures, or both (R/F). Usual intake of vitamin D included 20 IU/kg/day from parenteral nutrition or 400 IU/day supplementation with enteral feeding. Radiographs of both forearms and serum samples were obtained at 3, 6, 9, and 12 months. Twenty-two infants had R/F. At 3 months, significantly lower mean (+/- SEM) serum phosphorus levels (4.5 +/- 0.4 vs 6.1 +/- 0.2 mg/dl), higher 1,25-dihydroxyvitamin D (1,25-[OH]2D) concentrations (96 +/- 5 vs 77 +/- 4 pg/ml), and higher free 1,25-(OH)2D index (1,25-[OH]2D:vitamin D binding protein ratio; 5.2 +/- 0.3 x 10(5) vs 4.0 +/- 0.2 x 10(5] were found in the R/F group. These values returned to normal and were similar between groups on subsequent measurements. Serum calcium, magnesium, and 25-hydroxyvitamin D (25-OHD) concentrations were normal and similar between groups. In both groups, serum vitamin D binding concentrations increased initially but remained stable and normal beyond 6 months. We conclude that in very low birth weight infants with R/F, the vitamin D status (as indicated by serum 25-OHD concentrations) is normal, and that lowered serum phosphorus levels, higher serum 1,25-(OH)2D levels, and a higher free 1,25-(OH)2D index support the thesis that mineral deficiency (especially of phosphorus) may be important in the pathogenesis of R/F in small preterm infants.
Assuntos
Calcifediol/sangue , Calcitriol/sangue , Fraturas Ósseas/sangue , Recém-Nascido de Baixo Peso/sangue , Raquitismo/sangue , Proteína de Ligação a Vitamina D/sangue , Nutrição Enteral , Fraturas Ósseas/complicações , Humanos , Recém-Nascido , Nutrição Parenteral , Estudos Prospectivos , Raquitismo/complicações , Vitamina D/administração & dosagemAssuntos
Cálcio/urina , Fosfatos/sangue , Raquitismo , Raquitismo/sangue , Microglobulina beta-2/urina , Criança , Humanos , Masculino , Raquitismo/urina , SíndromeRESUMO
Seventy-four infants weighing less than 1500 gm at birth were fed enterally from birth until day 47. Group A (18 infants) were given SMA Gold Cap: group B (18 infants), supplementary calcium to 21 mmol/L (84 mg/dl); group C (16 infants), further calcium supplementation to 31.2 mmol/L (125 mg/dl); and group D (22 infants), milk with calcium content 31.2 mmol/L (125 mg/dl) and phosphorus supplementation to 15.7 mmol/L (49 mg/dl). The addition of calcium reduced the radiologic evidence of rickets, and combined calcium and phosphorus supplementation maintained plasma alkaline phosphatase activity within the normal range for 6 weeks.
Assuntos
Cálcio/uso terapêutico , Recém-Nascido de Baixo Peso , Fósforo/uso terapêutico , Raquitismo/tratamento farmacológico , Fosfatase Alcalina/sangue , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/metabolismo , Cálcio/administração & dosagem , Cálcio/sangue , Humanos , Alimentos Infantis , Recém-Nascido , Fosfatos/sangue , Fósforo/administração & dosagem , Radiografia , Raquitismo/sangue , Raquitismo/diagnóstico por imagemRESUMO
Serum calcidiol, calcitriol, and 24,25-dihydroxyvitamin D concentrations were measured in 20 children with vitamin D-deficiency rickets. Vitamin D metabolite concentrations were measured in 17 of 20 patients before treatment and in 14 of 20 patients after vitamin D administration. Conclusions are as follows. (1) Before treatment, serum calcidiol seems to be the best criterion of D deficiency, as it was low (less than 8 ng/ml) in 15 of 17 studied children, whereas calcitriol and 24,25-dihydroxyvitamin D concentrations ranged from undetectable to high values (350 pg/ml and 5.9 ng/ml, respectively). (2) Low calcidiol concentrations may occur despite recent vitamin D intake: low serum values were found in children given vitamin D2 up to two months after the onset of therapy (50 micrograms/day). (3) Elevated calcitriol serum concentrations were observed in all children after initiation of vitamin D therapy; these high concentrations persisted for four weeks or more, even after normalization of serum calcium, phosphorus, and parathyroid hormone values. (4) Healing of biochemical abnormalities can occur even in children with low circulating concentrations of calcidiol and 24,25-dihydroxyvitamin D.
Assuntos
Calcitriol/sangue , Ergocalciferóis/análogos & derivados , Raquitismo/sangue , 25-Hidroxivitamina D 2 , Cálcio/sangue , Criança , Pré-Escolar , Ergocalciferóis/sangue , Ergocalciferóis/uso terapêutico , Feminino , Humanos , Lactente , Masculino , Raquitismo/tratamento farmacológicoAssuntos
Calcitriol/sangue , Raquitismo/sangue , Envelhecimento , Cálcio/metabolismo , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Ritmo Circadiano , Glucocorticoides/metabolismo , Hormônio do Crescimento/metabolismo , Humanos , Hipofosfatemia Familiar/sangue , Recém-Nascido de Baixo Peso , Recém-Nascido , Doenças do Recém-Nascido/sangue , Hormônio Paratireóideo/metabolismo , Fosfatos/metabolismo , Prolactina/metabolismo , Raquitismo/genética , Vitamina D/administração & dosagem , Vitamina D/sangueRESUMO
Elevated 1,25 dihydroxyvitamin D concentrations were found in five VLBW infants who developed rickets at two to three months postnatal age or term postconceptual age; 25 hydroxyvitamin D concentrations were low. Bone mineralization was found to be extremely low as measured by infant-adapted direct photon absorptiometry. After treatment with a formula supplemented with additional Ca and P, there was a rapid improvement in bone mineralization with a concomitant decrease of 1,25(OH)2D to normal adult values, whereas 250HD values increased and parathyroid hormone values decreased. In the VLBW infants studied, we suggest that rickets may be caused by Ca and P deficiency rather than by a deficiency of vitamin D metabolism.