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Reduced muscle tone, muscle weakness, and physical fatigue can impact considerably on quality of life for children with neurofibromatosis type 1 (NF1). Human muscle biopsies and mouse models of NF1 deficiency in muscle show intramyocellular lipid accumulation, and preclinical data have indicated that L-carnitine supplementation can ameliorate this phenotype. The aim of this study is to examine whether daily L-carnitine supplementation is safe and feasible, and will improve muscle strength and reduce fatigue in children with NF1. A 12-week Phase 2a trial was conducted using 1000 mg daily oral levocarnitine tartrate supplementation. Recruited children were between 8 and 12 years old with a clinical diagnosis of NF1, history of muscle weakness and fatigue, and naïve to L-carnitine. Primary outcomes were safety (self-reporting, biochemical testing) and compliance. Secondary outcomes included plasma acylcarnitine profiles, functional measures (muscle strength, long jump, handwriting speed, 6-minute-walk test [6MWT]), and parent-reported questionnaires (PedsQL™, CBCL/6-18). Six children completed the trial with no self-reported adverse events. Biochemical tests for kidney and liver function were normal, and the average compliance was 95%. Plasma acylcarnitine levels were low, but within a range not clinically linked to carnitine deficiency. For strength measures, there was a mean 53% increase in dorsiflexion strength (95% confidence interval [CI] 8.89-60.75; p = 0.02) and mean 66% increase in plantarflexion strength (95% CI 12.99-134.1; p = 0.03). In terms of muscle performance, there was a mean 10% increase in long jump distance (95% CI 2.97-16.03; p = 0.01) and 6MWT distance (95% CI 5.88-75.45; p = 0.03). Comparison with the 1000 Norms Project data showed a significant improvement in Z-score for all of these measures. Parent reports showed no negative impact on quality of life, and the perceived benefits led to the majority of individuals remaining on L-carnitine after the study. Twelve weeks of L-carnitine supplementation is safe and feasible in children with NF1, and a Phase 3 trial should confirm the efficacy of treatment.
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Carnitina/administración & dosificación , Fatiga/dietoterapia , Debilidad Muscular/dietoterapia , Neurofibromatosis 1/dietoterapia , Cardiomiopatías/dietoterapia , Cardiomiopatías/metabolismo , Cardiomiopatías/patología , Carnitina/efectos adversos , Carnitina/deficiencia , Carnitina/metabolismo , Niño , Suplementos Dietéticos/efectos adversos , Fatiga/genética , Fatiga/patología , Femenino , Humanos , Hiperamonemia/dietoterapia , Hiperamonemia/metabolismo , Hiperamonemia/patología , Masculino , Fuerza Muscular/efectos de los fármacos , Debilidad Muscular/metabolismo , Debilidad Muscular/patología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiopatología , Enfermedades Musculares/dietoterapia , Enfermedades Musculares/metabolismo , Enfermedades Musculares/patología , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/metabolismo , Neurofibromatosis 1/patología , Calidad de VidaRESUMEN
OBJECTIVE: The aim of this study was to determine, retrospectively, the serum 25OHD and calcium concentrations of screened neonates of mothers at high risk of 25OHD deficiency and examine whether their measurement contributes to the management of these neonates. METHODS: Serum 25OHD and calcium concentrations from 600 samples of umbilical cord blood or venous blood collected from neonates over a 12-month period were analysed. RESULTS: There was a high prevalence of vitamin D insufficiency (27.6%, 30-50 nmol/L) and deficiency (21.3%, < 30 nmol/L) in neonates from high-risk maternal groups. There was a statistically positive but weak correlation (ρ = 0.22, P < 0.0001) between 25OHD and serum calcium. Only 7 neonates out of 569 (1.2%) had calcium concentrations in the hypocalcaemic range; however, a significant number (47.6%) were reported to be in the hypercalcaemic range. Nearly all of these were venous samples collected in first 24 h after birth. CONCLUSION: Vitamin D deficiency is prevalent in neonates of high-risk mothers but the risk of hypocalcaemia due to vitamin D deficiency at birth is low. Screening neonates entails blood testing which can cause distress to neonates and their parents, substantial imposition on staff and financial burden on the health care system. Vitamin D supplementation of these neonates from birth without routine screening appears more reasonable. Also, the data from this study suggest that the paediatric reference range for corrected calcium concentrations in neonates should be re-evaluated.
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Deficiencia de Vitamina D , Vitamina D , Calcio , Niño , Femenino , Humanos , Recién Nacido , Madres , Estudios Retrospectivos , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/epidemiologíaRESUMEN
In 2016, a global consensus on the prevention, diagnosis and management of nutritional rickets was published. The bone and mineral working group of the Australasian Paediatric Endocrine Group provides a summary and highlights differences to previous Australian and New Zealand (ANZ) guidelines on vitamin D deficiency and their implications for clinicians. Key points are: (i) The International Consensus document is focused on nutritional rickets, whereas the ANZ guidelines were focused on vitamin D deficiency. (ii) Definitions for the interpretation of 25-hydroxy vitamin D (25OHD) levels do not differ between statements. (iii) The global consensus recommends that routine 25OHD screening should not be performed in healthy children and recommendations for vitamin D supplementation are not based solely on 25OHD levels. The Australasian Paediatric Endocrine Group bone and mineral working group supports that screening for vitamin D deficiency should be restricted to populations at risk. (iv) Recommendations from the global consensus for vitamin D dosages for the therapy of nutritional rickets (diagnosed based on history, physical examination, biochemical testing and a confirmation by X-rays) are higher than in ANZ publications. (v) The global consensus recommends the implementation of public health strategies such as universal supplementation with vitamin D from birth to 1 year of age and food fortification. We conclude that updated global recommendations for therapy of nutritional rickets complement previously published position statements for Australia and New Zealand. Screening, management and the implementation of public health strategies need to be further explored for Australia.
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Raquitismo , Deficiencia de Vitamina D , Australia , Niño , Consenso , Humanos , Nueva Zelanda , Raquitismo/diagnóstico , Raquitismo/tratamiento farmacológico , Raquitismo/prevención & control , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/prevención & controlRESUMEN
Clinical concerns have been raised over prior exposure to bisphosphonates impairing fracture healing. To model this, groups of male Wistar rats were assigned to saline control or treatment groups receiving 0.15 mg/kg (low dose), 0.5 mg/kg (medium dose), and 5 mg/kg (high dose) Pamidronate (PAM) twice weekly for 4 weeks. At this point, closed fractures were made using an Einhorn apparatus, and bisphosphonate dosing was continued until the experimental endpoint. Specimens were analyzed at 2 and 6 weeks (N = 8 per group per time point). Twice weekly PAM dosing was found to have no effect on early soft callus remodeling at 2 weeks post fracture. At this time point, the highest dose PAM group gave significant increases in bone volume (+ 10%, p < 0.05), bone mineral content (+ 30%, p < 0.01), and bone mineral density (+ 10%, p < 0.01). This PAM dosing regimen showed more substantive effects on hard callus at 6 weeks post fracture, with PAM treatment groups showing + 46-79% increased bone volume. Dynamic bone labeling showed reduced calcein signal in the PAM-treated calluses (38-63%, p < 0.01) and reduced MAR (32-49%, p < 0.01), suggesting a compensatory reduction in bone anabolism. These data support the concept that bisphosphonates lead to profound decreases in bone turnover in fracture repair, however, this does not affect soft callus remodeling.
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Callo Óseo/efectos de los fármacos , Fracturas del Fémur/patología , Fracturas Cerradas/patología , Osteogénesis/efectos de los fármacos , Pamidronato/farmacología , Animales , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/farmacología , Remodelación Ósea/efectos de los fármacos , Callo Óseo/patología , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Fracturas del Fémur/tratamiento farmacológico , Curación de Fractura/efectos de los fármacos , Fracturas Cerradas/tratamiento farmacológico , Masculino , Tamaño de los Órganos/efectos de los fármacos , Osteogénesis Imperfecta/patología , Pamidronato/administración & dosificación , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
FGF23 is an important hormonal regulator of phosphate homeostasis. Together with its co-receptor Klotho, it modulates phosphate reabsorption and both 1α-hydroxylation and 24-hydroxylation in the renal proximal tubules. The most common FGF23-mediated hypophosphatemia is X-linked hypophosphatemia (XLH), caused by mutations in the PHEX gene. FGF23-mediated forms of hypophosphatemia are characterized by phosphaturia and low or low-normal calcitriol concentrations, and unlike nutritional rickets, these cannot be cured with nutritional vitamin D supplementation. Autosomal dominant and autosomal recessive forms of FGF23-mediated hypophosphatemias show a similar pathophysiology, despite a variety of different underlying genetic causes. An excess of FGF23 activity has also been associated with a number of other conditions causing hypophosphatemia, including tumor-induced osteomalacia, fibrous dysplasia of the bone, and cutaneous skeletal hypophosphatemia syndrome. Historically phosphate supplementation and therapy using analogs of highly active vitamin D (eg, calcitriol, alfacalcidol, paricalcitol, eldecalcitol) have been used to manage conditions involving hypophosphatemia; however, recently a neutralizing antibody for FGF23 (burosumab) has emerged as a promising treatment agent for FGF23-mediated disorders. This review discusses the progression of clinical trials for burosumab for the treatment of XLH and its recent availability for clinical use. Burosumab may have potential for treating other conditions associated with FGF23 overactivity, but these are not yet supported by trial data. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
RESUMEN
The etiology of endemic rickets was discovered a century ago. Vitamin D is the precursor of 25-hydroxyvitamin D and other metabolites, including 1,25(OH)2D, the ligand for the vitamin D receptor (VDR). The effects of the vitamin D endocrine system on bone and its growth plate are primarily indirect and mediated by its effect on intestinal calcium transport and serum calcium and phosphate homeostasis. Rickets and osteomalacia can be prevented by daily supplements of 400 IU of vitamin D. Vitamin D deficiency (serum 25-hydroxyvitamin D <50 nmol/L) accelerates bone turnover, bone loss, and osteoporotic fractures. These risks can be reduced by 800 IU of vitamin D together with an appropriate calcium intake, given to institutionalized or vitamin D-deficient elderly subjects. VDR and vitamin D metabolic enzymes are widely expressed. Numerous genetic, molecular, cellular, and animal studies strongly suggest that vitamin D signaling has many extraskeletal effects. These include regulation of cell proliferation, immune and muscle function, skin differentiation, and reproduction, as well as vascular and metabolic properties. From observational studies in human subjects, poor vitamin D status is associated with nearly all diseases predicted by these extraskeletal actions. Results of randomized controlled trials and Mendelian randomization studies are supportive of vitamin D supplementation in reducing the incidence of some diseases, but, globally, conclusions are mixed. These findings point to a need for continued ongoing and future basic and clinical studies to better define whether vitamin D status can be optimized to improve many aspects of human health. Vitamin D deficiency enhances the risk of osteoporotic fractures and is associated with many diseases. We review what is established and what is plausible regarding the health effects of vitamin D.
Asunto(s)
Huesos/metabolismo , Calcio/metabolismo , Vitamina D/metabolismo , Animales , Huesos/fisiología , Femenino , Humanos , Masculino , Osteomalacia/tratamiento farmacológico , Osteomalacia/prevención & control , Raquitismo/tratamiento farmacológico , Raquitismo/prevención & control , Transducción de Señal , Vitamina D/fisiología , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/prevención & controlAsunto(s)
Emigrantes e Inmigrantes , Etnicidad , Alimentos Fortificados , Osteomalacia/prevención & control , Raquitismo/prevención & control , Calcio de la Dieta/administración & dosificación , Europa (Continente) , Humanos , Osteomalacia/etnología , Salud Pública , Raquitismo/etnología , Factores de Riesgo , Vitamina D/administración & dosificaciónRESUMEN
BACKGROUND: Vitamin D and calcium deficiencies are common worldwide, causing nutritional rickets and osteomalacia, which have a major impact on health, growth, and development of infants, children, and adolescents; the consequences can be lethal or can last into adulthood. The goals of this evidence-based consensus document are to provide health care professionals with guidance for prevention, diagnosis, and management of nutritional rickets and to provide policy makers with a framework to work toward its eradication. EVIDENCE: A systematic literature search examining the definition, diagnosis, treatment, and prevention of nutritional rickets in children was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system that describe the strength of the recommendation and the quality of supporting evidence. PROCESS: Thirty-three nominated experts in pediatric endocrinology, pediatrics, nutrition, epidemiology, public health, and health economics evaluated the evidence on specific questions within five working groups. The consensus group, representing 11 international scientific organizations, participated in a multiday conference in May 2014 to reach a global evidence-based consensus. RESULTS: This consensus document defines nutritional rickets and its diagnostic criteria and describes the clinical management of rickets and osteomalacia. Risk factors, particularly in mothers and infants, are ranked, and specific prevention recommendations including food fortification and supplementation are offered for both the clinical and public health contexts. CONCLUSION: Rickets, osteomalacia, and vitamin D and calcium deficiencies are preventable global public health problems in infants, children, and adolescents. Implementation of international rickets prevention programs, including supplementation and food fortification, is urgently required.
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Ingesta Diaria Recomendada , Raquitismo/prevención & control , Calcio/deficiencia , Niño , Preescolar , Consenso , Política de Salud , Humanos , Lactante , Madres , Osteomalacia/diagnóstico , Osteomalacia/terapia , Raquitismo/terapia , Factores de Riesgo , Vitamina D/administración & dosificación , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/terapia , Vitaminas/administración & dosificación , Vitaminas/uso terapéuticoRESUMEN
BACKGROUND: Vitamin D and calcium deficiencies are common worldwide, causing nutritional rickets and osteomalacia, which have a major impact on health, growth, and development of infants, children, and adolescents; the consequences can be lethal or can last into adulthood. The goals of this evidence-based consensus document are to provide health care professionals with guidance for prevention, diagnosis, and management of nutritional rickets and to provide policy makers with a framework to work toward its eradication. EVIDENCE: A systematic literature search examining the definition, diagnosis, treatment, and prevention of nutritional rickets in children was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system that describes the strength of the recommendation and the quality of supporting evidence. PROCESS: Thirty-three nominated experts in pediatric endocrinology, pediatrics, nutrition, epidemiology, public health, and health economics evaluated the evidence on specific questions within five working groups. The consensus group, representing 11 international scientific organizations, participated in a multiday conference in May 2014 to reach a global evidence-based consensus. RESULTS: This consensus document defines nutritional rickets and its diagnostic criteria and describes the clinical management of rickets and osteomalacia. Risk factors, particularly in mothers and infants, are ranked, and specific prevention recommendations including food fortification and supplementation are offered for both the clinical and public health contexts. CONCLUSION: Rickets, osteomalacia, and vitamin D and calcium deficiencies are preventable global public health problems in infants, children, and adolescents. Implementation of international rickets prevention programs, including supplementation and food fortification, is urgently required.
Asunto(s)
Raquitismo/terapia , Calcio/deficiencia , Femenino , Humanos , Lactancia , Embarazo , Complicaciones del Embarazo/prevención & control , Salud Pública , Raquitismo/diagnóstico , Raquitismo/etiología , Factores de Riesgo , Deficiencia de Vitamina D/complicacionesRESUMEN
Immigrant and refugee populations bring public health challenges to host nations. In the current global refugee crisis, children are the most vulnerable subpopulation. Diseases that were considered rare in the host nation may be highly prevalent among immigrant children. The prevalence of nutritional rickets is increasing in high-income countries, largely driven by an influx of immigrant populations. Nutritional rickets is a bone disease in early childhood resulting in bone pain, delayed motor development, and bending of the bones, caused by vitamin D deficiency and/or inadequate dietary calcium intake. The consequences of nutritional rickets include stunted growth, developmental delay, lifelong bone deformities, seizures, cardiomyopathy, and even death. Nutritional rickets is most commonly seen in children from the Middle East, Africa, and South Asia in high-income countries. Dark skin pigmentation, sun avoidance, covering the skin, and prolonged breast feeding without vitamin D supplementation, are important risk factors for vitamin D deficiency, and combined with a lack of dairy products in the diet, these deficiencies can result in insufficient calcium supply for bone mineralization. We recommend screening all immigrant and refugee children under 5 years of age from these ethnic groups for nutritional rickets, based on clinical features, and confirming the diagnosis with radiographs of the wrists and knees. Because nutritional rickets is entirely preventable, public health policies must address the need for universal vitamin D supplementation and adequate dietary calcium to protect children from this scourge. Vitamin D supplementation of all infants and children with 400 IU/d during the first year of life and dietary or supplemental intakes of at least 600 IU/d of vitamin D and 500 mg/d of calcium thereafter, will effectively prevent nutritional rickets. We call on national health authorities of host countries to implement health check lists and prevention programs that include screening for micronutrient deficiencies, in addition to assessing infections and vaccination programs. Due to their high prevalence of vitamin D deficiency, refugee children of all ages from these ethnic groups should be supplemented with vitamin D, beginning upon arrival.
RESUMEN
OBJECTIVE: Vitamin D deficiency in pregnancy is associated with an increased risk of gestational diabetes mellitus (GDM) and neonatal vitamin D deficiency. We conducted a double-blind, randomized controlled trial of low-dose (LD) versus high-dose (HD) vitamin D supplementation to investigate the effects of vitamin D supplementation on glucose metabolism during pregnancy. RESEARCH DESIGN AND METHODS: Women with plasma 25-hydroxyvitamin D (25OHD) levels <32 ng/mL before 20 weeks' gestation were randomized to oral vitamin D3 at 5,000 IU daily (HD) (n = 89) or the recommended pregnancy dose of 400 IU daily (LD) (n = 90) until delivery. The primary end point was maternal glucose levels on oral glucose tolerance test (OGTT) at 26-28 weeks' gestation. Secondary end points included neonatal 25OHD, obstetric and other neonatal outcomes, and maternal homeostasis model assessment of insulin resistance. Analysis was by intention to treat. RESULTS: There was no difference in maternal glucose levels on OGTT. Twelve LD women (13%) developed GDM versus seven (8%) HD women (P = 0.25). Neonatal cord 25OHD was higher in HD offspring (46 ± 11 vs. 29 ± 12 ng/mL, P < 0.001), and deficiency was more common in LD offspring (24 vs. 10%, P = 0.06). Post hoc analysis in LD women showed an inverse relationship between pretreatment 25OHD and both fasting and 2-h blood glucose level on OGTT (both P < 0.001). Baseline 25OHD remained an independent predictor after multiple regression analysis. CONCLUSIONS: HD vitamin D supplementation commencing at a mean of 14 weeks' gestation does not improve glucose levels in pregnancy. However, in women with baseline levels <32 ng/mL, 5,000 IU per day was well tolerated and highly effective at preventing neonatal vitamin D deficiency.
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Colecalciferol/uso terapéutico , Diabetes Gestacional/prevención & control , Deficiencia de Vitamina D/tratamiento farmacológico , Vitamina D/análogos & derivados , Adulto , Colecalciferol/administración & dosificación , Colecalciferol/efectos adversos , Diabetes Gestacional/epidemiología , Diabetes Gestacional/etiología , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Ayuno , Femenino , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Humanos , Resistencia a la Insulina , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones , Adulto JovenRESUMEN
BACKGROUND: The genetic mutation resulting in osteogenesis imperfecta (OI) type V was recently characterised as a single point mutation (c.-14C > T) in the 5' untranslated region (UTR) of IFITM5, a gene encoding a transmembrane protein with expression restricted to skeletal tissue. This mutation creates an alternative start codon and has been shown in a eukaryotic cell line to result in a longer variant of IFITM5, but its expression has not previously been demonstrated in bone from a patient with OI type V. METHODS: Sanger sequencing of the IFITM5 5' UTR was performed in our cohort of subjects with a clinical diagnosis of OI type V. Clinical data was collated from referring clinicians. RNA was extracted from a bone sample from one patient and Sanger sequenced to determine expression of wild-type and mutant IFITM5. RESULTS: All nine subjects with OI type V were heterozygous for the c.-14C > T IFITM5 mutation. Clinically, there was heterogeneity in phenotype, particularly in the manifestation of bone fragility amongst subjects. Both wild-type and mutant IFITM5 mRNA transcripts were present in bone. CONCLUSIONS: The c.-14C > T IFITM5 mutation does not result in an RNA-null allele but is expressed in bone. Individuals with identical mutations in IFITM5 have highly variable phenotypic expression, even within the same family.
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Regiones no Traducidas 5'/genética , Huesos/metabolismo , Osteogénesis Imperfecta/genética , Mutación Puntual , ARN Mensajero/biosíntesis , Adolescente , Adulto , Densidad Ósea , Callo Óseo/patología , Calcinosis/etiología , Niño , Codón Iniciador/genética , ADN Complementario/genética , Femenino , Fracturas Espontáneas/etiología , Genes Dominantes , Heterocigoto , Humanos , Hiperplasia , Luxaciones Articulares/etiología , Masculino , Persona de Mediana Edad , Osteogénesis Imperfecta/complicaciones , Fenotipo , ARN Mensajero/genética , Radio (Anatomía) , Análisis de Secuencia de ADNRESUMEN
⢠The recommended level for serum 25-hydroxyvitamin D (25(OH)D) in infants, children, adolescents and during pregnancy and lactation is ≥ 50 nmol/L. This level may need to be 10-20 nmol/L higher at the end of summer to maintain levels ≥ 50 nmol/L over winter and spring. ⢠Sunlight is the most important source of vitamin D. The US recommended dietary allowance for vitamin D is 600 IU daily in children aged over 12 months and during pregnancy and lactation, assuming minimal sun exposure. ⢠Risk factors for low vitamin D are: lack of skin exposure to sunlight, dark skin, southerly latitude, conditions affecting vitamin D metabolism and storage (including obesity) and, for infants, being born to a mother with low vitamin D and exclusive breastfeeding combined with at least one other risk factor. ⢠Targeted measurement of 25(OH)D levels is recommended for infants, children and adolescents with at least one risk factor for low vitamin D and for pregnant women with at least one risk factor for low vitamin D at the first antenatal visit. ⢠Vitamin D deficiency can be treated with daily low-dose vitamin D supplements, although barriers to adherence have been identified. High-dose intermittent vitamin D can be used in children and adolescents. Treatment should be paired with health education and advice about sensible sun exposure. Infants at risk of low vitamin D should be supplemented with 400 IU vitamin D3 daily for at least the first year of life. ⢠There is increasing evidence of an association between low vitamin D and a range of non-bone health outcomes, however there is a lack of data from robust randomised controlled trials of vitamin D supplementation.
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Vitamina D/sangre , Vitaminas/sangre , Adolescente , Australia/epidemiología , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Nueva Zelanda/epidemiología , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/terapia , Vitamina D/fisiología , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/terapia , Vitaminas/fisiologíaRESUMEN
OBJECTIVE: To describe the natural history of vitamin D deficiency in an at-risk population of African migrants living in Sydney. DESIGN, SETTING AND PARTICIPANTS: Opportunistic study of 25-hydroxyvitamin D [25(OH)D] concentrations over time in a community-based cohort of North African refugee families living in south-western Sydney. As part of a health-screening program, serum concentrations of 25(OH)D, parathyroid hormone (PTH), calcium, phosphate (PO(4)) and alkaline phosphatase (ALP) were measured in September 2006 (end of winter, T1). Results for 25(OH)D were made available, and treatment was recommended as appropriate. In February-March 2007 (end of summer, T2), in the setting of a separate study of high-dose vitamin D (stoss) therapy, the same cohort was contacted, and measurements were repeated. MAIN OUTCOME MEASURES: Changes in 25(OH)D, PTH, ALP and PO(4) concentrations between T1 and T2 in those who had not received vitamin D supplementation in the intervening period. RESULTS: We collected data from 149 participants at T1; by T2, 58 participants (39%) had been excluded or lost to follow-up. Data from 91 participants (46% female), all of whom had Type VI (very dark) skin pigmentation, were included in the analysis. All 91 were 25(OH)D deficient at T1. Between T1 and T2, mean 25(OH)D serum concentration increased from 19 nmol/L (SD, 5.6 nmol/L) to 36 nmol/L (SD, 12.4 nmol/L) (P < 0.001). Of the 91 participants, 79 (87%) remained vitamin D deficient at T2. Serum PTH and ALP activity decreased between T1 and T2 (P < 0.05). CONCLUSION: Despite a significant increase in 25(OH)D serum concentration over the study period, most participants (87%) remained 25(OH)D deficient at the end of summer. Our results support the current consensus that recommends annual screening for vitamin D deficiency and routine vitamin D supplementation in at-risk populations, such as dark-skinned or veiled groups.
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Población Negra/estadística & datos numéricos , Refugiados/estadística & datos numéricos , Estaciones del Año , Deficiencia de Vitamina D/etnología , Adolescente , Adulto , África del Norte/etnología , Factores de Edad , Australia , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Características de la Residencia , Factores Sexuales , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/diagnósticoRESUMEN
BACKGROUND: A baby girl developed respiratory distress immediately after birth and required supplemental oxygen. She was born at term via lower-segment cesarean section. The parents were nonconsanguineous, and antenatal ultrasonography during the pregnancy at 18 and 32 weeks of gestation did not reveal any abnormalities. On examination at birth, no pulses were palpable; however, the baby's blood pressure was normal and no remarkable abnormalities were detected. Ultrasonography revealed widespread arterial calcification. INVESTIGATIONS: Chest and abdominal radiography at birth and serial abdominal, renal and cardiac ultrasonography at follow-up examinations; dual-energy X-ray absorptiometry during treatment with bisphosphonates; genetic screening. DIAGNOSIS: Generalized arterial calcification of infancy, secondary to compound, heterozygous mutations in the ENPP1 gene, pL661V and pE668K of the paternal chromosome, and pN792S in the maternal chromosome. MANAGEMENT: Low-dose disodium pamidronate (0.1 mg/kg per week for 4 weeks), which commenced on the seventh day after birth and was changed to oral risedronate sodium (1 mg/kg per week as a single dose) at 4 weeks of age. Complete resolution of arterial calcification was seen by 3 months of age. At 12 months, ergocalciferol was added at a dose of 5,000 U daily for 6 weeks, followed by 200 U daily owing to the patient's vitamin D deficiency and elevated parathyroid hormone level. Treatment with bisphosphonates is ongoing, but is planned to be discontinued at 3 years of age. The child has remained healthy and developmentally normal.