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1.
Eur J Endocrinol ; 184(5): K15-K20, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33690157

RESUMO

INTRODUCTION: Autosomal recessive forms of pseudohypoaldosteronism are caused by genetic defects in the epithelial sodium channel. Little is known about the long-term outcome and medication needs during childhood and adolescence. OBJECTIVE: This study reports a single-centre experience of children affected with this ultra-rare condition over a 37-year period. METHODS: We report the clinical presentation, growth, neuro-development, associated conditions, mortality and medication dosing and administration for 12 affected children from eight families. RESULTS: All children were presented within the first 2 weeks of life with life-threatening, severe hyperkalaemia and hyponatraemia. All parents were consanguineous and of South Asian, Middle Eastern or African ethnic origin. Eight children had homozygous mutations in the SCNN1A and SCNN1G genes, encoding the epithelial sodium channel subunits alpha and gamma, respectively, including one novel mutation. Three children died (25%) and two (16%) had severe neurological impairment post-cardiac arrest secondary to hyperkalaemia. One affected female had a successful pregnancy at the age of 28 years. CONCLUSION: Despite high mortality and morbidity in this condition, survival with normal physical and neurological outcome is possible, justifying intensive management to prevent electrolyte imbalance.


Assuntos
Pseudo-Hipoaldosteronismo/diagnóstico , Pseudo-Hipoaldosteronismo/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Consanguinidade , Canais Epiteliais de Sódio/genética , Família , Feminino , Genes Recessivos , Homozigoto , Humanos , Masculino , Mutação , Pseudo-Hipoaldosteronismo/genética , Pseudo-Hipoaldosteronismo/mortalidade , Estudos Retrospectivos , Reino Unido/epidemiologia , Adulto Jovem
2.
Eur J Endocrinol ; 180(3): 213-221, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30566905

RESUMO

Objective Androgen excess in childhood is a common presentation and may signify sinister underlying pathology. Data describing its patterns and severity are scarce, limiting the information available for clinical decision processes. Here, we examined the differential diagnostic value of serum DHEAS, androstenedione (A4) and testosterone in childhood androgen excess. Design Retrospective review of all children undergoing serum androgen measurement at a single center over 5 years. Methods Serum A4 and testosterone were measured by tandem mass spectrometry and DHEAS by immunoassay. Patients with at least one increased androgen underwent phenotyping by clinical notes review. Results In 487 children with simultaneous DHEAS, A4 and testosterone measurements, we identified 199 with androgen excess (140 pre- and 59 post-pubertal). Premature adrenarche (PA) was the most common pre-pubertal diagnosis (61%), characterized by DHEAS excess in 85%, while A4 and testosterone were only increased in 26 and 9% respectively. PCOS was diagnosed in 40% of post-pubertal subjects, presenting equally frequent with isolated excess of DHEAS (29%) or testosterone (25%) or increases in both A4 and testosterone (25%). CAH patients (6%) predominantly had A4 excess (86%); testosterone and DHEAS were increased in 50 and 33% respectively. Concentrations increased above the two-fold upper limit of normal were mostly observed in PA for serum DHEAS (>20-fold in the single case of adrenocortical carcinoma) and in CAH for serum androstenedione. Conclusions Patterns and severity of childhood androgen excess provide pointers to the underlying diagnosis and can be used to guide further investigations.


Assuntos
Androgênios/sangue , Doenças do Sistema Endócrino/epidemiologia , Doenças do Sistema Endócrino/etiologia , Puberdade/sangue , Adolescente , Androstenodiona/sangue , Criança , Pré-Escolar , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona/sangue , Doenças do Sistema Endócrino/sangue , Doenças do Sistema Endócrino/patologia , Feminino , Humanos , Masculino , Puberdade Precoce/sangue , Puberdade Precoce/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Maturidade Sexual/fisiologia , Testosterona/sangue
3.
J Clin Invest ; 128(5): 1913-1918, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29461981

RESUMO

Genetic forms of vitamin D-dependent rickets (VDDRs) are due to mutations impairing activation of vitamin D or decreasing vitamin D receptor responsiveness. Here we describe two unrelated patients with early-onset rickets, reduced serum levels of the vitamin D metabolites 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and deficient responsiveness to parent and activated forms of vitamin D. Neither patient had a mutation in any genes known to cause VDDR; however, using whole exome sequencing analysis, we identified a recurrent de novo missense mutation, c.902T>C (p.I301T), in CYP3A4 in both subjects that alters the conformation of substrate recognition site 4 (SRS-4). In vitro, the mutant CYP3A4 oxidized 1,25-dihydroxyvitamin D with 10-fold greater activity than WT CYP3A4 and 2-fold greater activity than CYP24A1, the principal inactivator of vitamin D metabolites. As CYP3A4 mutations have not previously been linked to rickets, these findings provide insight into vitamin D metabolism and demonstrate that accelerated inactivation of vitamin D metabolites represents a mechanism for vitamin D deficiency.


Assuntos
Calcitriol , Citocromo P-450 CYP3A , Exoma , Mutação , Raquitismo , Vitamina D/análogos & derivados , Calcitriol/genética , Calcitriol/metabolismo , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Feminino , Células HEK293 , Humanos , Masculino , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Raquitismo/enzimologia , Raquitismo/genética , Vitamina D/genética , Vitamina D/metabolismo , Vitamina D3 24-Hidroxilase/genética , Vitamina D3 24-Hidroxilase/metabolismo , Sequenciamento Completo do Genoma
4.
Arch Dis Child ; 103(1): 92-94, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28988216

RESUMO

Intravenous pamidronate has been used in the treatment of osteogenesis imperfecta (OI) in children for over 20 years. The more potent zoledronate is an attractive alternative as it is administered less frequently. This study compares the clinical efficacy of intravenous pamidronate (1.5 mg/kg/day over 2 days, every 3 months) versus zoledronate (0.05 mg/kg/dose every 6 months) in 40 children (20 per group) with mild to moderate OI and the treatment costs of the two drugs in a tertiary centre for children with osteoporosis. Lumbar spine bone mineral density and fracture rate did not differ between drug groups following 1 and 2 years of treatment, respectively. Total cost per treatment course per patient was £1157 for pamidronate and £498 for zoledronate. Therefore, zoledronate is a considerably cheaper alternative to pamidronate with comparable efficacy, resulting in substantial annual savings for healthcare providers and a more convenient option for patients due to fewer hospital visits.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Osteoporose/tratamento farmacológico , Administração Intravenosa , Densidade Óssea , Conservadores da Densidade Óssea/economia , Criança , Difosfonatos/economia , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Imidazóis/economia , Masculino , Pamidronato , Estudos Retrospectivos , Ácido Zoledrônico
5.
J Bone Miner Res ; 32(1): 172-180, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27490028

RESUMO

The increasing use of dual-energy X-ray absorptiometry (DXA) in children has led to the need for robust reference data for interpretation of scans in daily clinical practice. Such data need to be representative of the population being studied and be "future-proofed" to software and hardware upgrades. The aim was to combine all available pediatric DXA reference data from seven UK centers to create reference curves adjusted for age, sex, ethnicity, and body size to enable clinical application, using in vivo cross-calibration and making data back and forward compatible. Seven UK sites collected data on GE Lunar or Hologic Scanners between 1996 and 2012. Males and females aged 4 to 20 years were recruited (n = 3598). The split by ethnic group was white 2887; South Asian 385; black Afro-Caribbean 286; and mixed heritage 40. Scans of the total body and lumbar spine (L1 to L4 ) were obtained. The European Spine Phantom was used to cross-calibrate the 7 centers and 11 scanners. Reference curves were produced for L1 to L4 bone mineral apparent density (BMAD) and total body less head (TBLH) and L1 to L4 areal bone mineral density (aBMD) for GE Lunar Prodigy and iDXA (sex- and ethnic-specific) and for Hologic (sex-specific). Regression equations for TBLH BMC were produced using stepwise linear regression. Scans of 100 children were randomly selected to test backward and forward compatibility of software versions, up to version 15.0 for GE Lunar and Apex 4.1 for Hologic. For the first time, sex- and ethnic-specific reference curves for lumbar spine BMAD, aBMD, and TBLH aBMD are provided for both GE Lunar and Hologic scanners. These curves will facilitate interpretation of DXA data in children using methods recommended in ISCD guidelines. The databases have been created to allow future updates and analysis when more definitive evidence for the best method of fracture prediction in children is agreed. © 2016 American Society for Bone and Mineral Research.


Assuntos
Tamanho Corporal , Osso e Ossos/anatomia & histologia , Densitometria , Absorciometria de Fóton , Adolescente , Antropometria , Densidade Óssea , Criança , Pré-Escolar , Feminino , Humanos , Vértebras Lombares/fisiologia , Masculino , Imagens de Fantasmas , Valores de Referência , Adulto Jovem
6.
PLoS Genet ; 12(7): e1006156, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27441836

RESUMO

Recessive osteogenesis imperfecta (OI) is caused by defects in proteins involved in post-translational interactions with type I collagen. Recently, a novel form of moderately severe OI caused by null mutations in TMEM38B was identified. TMEM38B encodes the ER membrane monovalent cation channel, TRIC-B, proposed to counterbalance IP3R-mediated Ca2+ release from intracellular stores. The molecular mechanisms by which TMEM38B mutations cause OI are unknown. We identified 3 probands with recessive defects in TMEM38B. TRIC-B protein is undetectable in proband fibroblasts and osteoblasts, although reduced TMEM38B transcripts are present. TRIC-B deficiency causes impaired release of ER luminal Ca2+, associated with deficient store-operated calcium entry, although SERCA and IP3R have normal stability. Notably, steady state ER Ca2+ is unchanged in TRIC-B deficiency, supporting a role for TRIC-B in the kinetics of ER calcium depletion and recovery. The disturbed Ca2+ flux causes ER stress and increased BiP, and dysregulates synthesis of proband type I collagen at multiple steps. Collagen helical lysine hydroxylation is reduced, while telopeptide hydroxylation is increased, despite increased LH1 and decreased Ca2+-dependent FKBP65, respectively. Although PDI levels are maintained, procollagen chain assembly is delayed in proband cells. The resulting misfolded collagen is substantially retained in TRIC-B null cells, consistent with a 50-70% reduction in secreted collagen. Lower-stability forms of collagen that elude proteasomal degradation are not incorporated into extracellular matrix, which contains only normal stability collagen, resulting in matrix insufficiency. These data support a role for TRIC-B in intracellular Ca2+ homeostasis, and demonstrate that absence of TMEM38B causes OI by dysregulation of calcium flux kinetics in the ER, impacting multiple collagen-specific chaperones and modifying enzymes.


Assuntos
Cálcio/metabolismo , Colágeno Tipo I/biossíntese , Canais Iônicos/genética , Osteogênese Imperfeita/genética , Adulto , Sinalização do Cálcio , Colágeno Tipo I/metabolismo , Consanguinidade , Análise Mutacional de DNA , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático , Feminino , Genes Recessivos , Estudos de Associação Genética , Predisposição Genética para Doença , Homeostase , Humanos , Lactente , Masculino , Linhagem , Processamento de Proteína Pós-Traducional
7.
Artigo em Inglês | MEDLINE | ID: mdl-26843960

RESUMO

UNLABELLED: Estrogen is used to induce puberty in peripubertal girls with hypogonadism. Although both synthetic and natural forms are available, along with different routes of administration, in the UK oral ethinyl estradiol and the low-dose oral contraceptive pill are commonly used as hormone replacement therapy for practical reasons. We present five peripubertal girls (aged 12.5-14.9 years) with hypogonadism (two with primary hypogonadism due to Turner syndrome and three with central (secondary) hypogonadism as part of multiple pituitary hormone deficiency) who for a variety of reasons have received milligram doses of estradiol (E2) in error for between 6 weeks and 6 months, instead of the expected microgram doses of ethinyl estradiol. Although there are no direct comparisons in peripubertal girls between synthetic and natural estrogens, all girls had vaginal bleeding whilst receiving the milligram doses and have ended up with reduced final heights, below the 9th centile in 1 and below the 2nd centile in 4. Whilst reduction in final height may be part of the underlying condition (especially in Turner syndrome) the two girls with height predictions performed prior to receiving the estrogen overdose have not achieved their predicted height. Estrogen is one of the few drugs which is available in both milligram and microgram formulations. Clinicians need to be alert to the possibility of patients receiving the wrong formulation and dosage in error. LEARNING POINTS: Girls with primary and secondary gonadal failure require assistance with pubertal induction.Although several different formulations and route of administration are available, for practical reasons, the majority of girls in the UK receive oral ethinyl estradiol.Estrogen preparations are available in both milligram and microgram formulations, with potential for receiving the wrong dose.Girls receiving milligram rather than microgram preparations all had vaginal bleeding and a short final height.

8.
J Pediatr ; 172: 181-186.e1, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26896157

RESUMO

OBJECTIVES: To explore the role of laboratory screening for hypophosphatasia and propose a diagnostic pathway for children with low serum alkaline phosphatase (ALP) activities. STUDY DESIGN: A retrospective hospital-based study over an 8-year period was conducted to identify children younger than 16 years of age with low ALP activity (<100 U/L). Study-positive patients were contacted for repeat sampling, and those with persistently low ALP had plasma pyridoxal-5'-phosphate and urinary phosphoethanolamine measured. RESULTS: Of 323 064 analyzed samples, 1526 had ALP activities <100 U/L. Most patients had transient hypophosphatasemia. Of 50 patients with last-recorded ALP <100 U/L, 32 were excluded given previous ALP >100 U/L. Eighteen were identified as study-positive. Of the 15 surviving children, 13 were traceable. Four had persistently low ALP activity on retesting, of whom 2 had raised pyridoxal-5'-phosphate and phosphoethanolamine concentrations and were subsequently tested for ALPL gene mutations; a 4-year-old asymptomatic girl with a novel homozygous ALPL missense mutation and a 23-year-old female with a heterozygous mutation. There was significant overlap in ALP activities between study-positive and 11 current patients with hypophosphatasia. We propose a diagnostic algorithm for children with low ALP activities based on clinical and biochemical variables. CONCLUSIONS: Patients with persistently low ALP activity require further clinical, biochemical, and radiological assessment for hypophosphatasia, even in the absence of clinical symptoms. The proposed diagnostic algorithm for children with low ALP will facilitate early detection of cases of hypophosphatasia, which, with the availability of enzyme replacement for hypophosphatasia, can be life-saving or avoid years of undiagnosed morbidity.


Assuntos
Fosfatase Alcalina/sangue , Hipofosfatasia/diagnóstico , Programas de Rastreamento/métodos , Adolescente , Algoritmos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Estudos Retrospectivos
10.
J Pediatr Endocrinol Metab ; 28(7-8): 967-70, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25741938

RESUMO

Autosomal recessive hypophosphatemic rickets 2 (ARHR2) is a rare form of renal tubular phosphate wasting disorder. Loss of function mutations of the ecto-nucleotide pyrophosphatase/pyrophosphodiesterase 1 gene (ENPP1) causes a wide spectrum of phenotypes, ranging from lethal generalized arterial calcification of infancy to hypophosphatemic rickets with hypertension. Hearing loss was not previously thought to be one of the features of the disease entities and was merely regarded as a complication rather than a part of the disease. We report two children who presented in mid to late childhood with progressive varus deformity of their legs due to hypophosphatemic rickets caused by mutations in the ENPP1 gene. Both children had evidence of progressive hearing loss requiring the use of hearing aids. This report of two unrelated infants with compound heterozygous mutations in ENPP1 and previously published cases confirms that mild to moderate hearing loss is frequently associated with ARHR2. Early onset conductive hearing loss may further distinguish the autosomal recessive ENPP1 related type from other types of hypophosphatemia.


Assuntos
Raquitismo Hipofosfatêmico Familiar/complicações , Raquitismo Hipofosfatêmico Familiar/genética , Perda Auditiva/etiologia , Mutação/genética , Diester Fosfórico Hidrolases/genética , Pirofosfatases/genética , Idade de Início , Feminino , Perda Auditiva/patologia , Heterozigoto , Humanos , Recém-Nascido , Masculino , Prognóstico
12.
J Bone Miner Res ; 29(12): 2601-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24919763

RESUMO

Among the high bone mass disorders, the osteopetroses reflect osteoclast failure that prevents skeletal resorption and turnover, leading to reduced bone growth and modeling and characteristic histopathological and radiographic findings. We report an 11-year-old boy with a new syndrome that radiographically mimics osteopetrosis (OPT), but features rapid skeletal turnover. He presented at age 21 months with a parasellar, osteoclast-rich giant cell granuloma. Radiographs showed a dense skull, generalized osteosclerosis and cortical thickening, medullary cavity narrowing, and diminished modeling of tubular bones. His serum alkaline phosphatase was >5000 IU/L (normal <850 IU/L). After partial resection, the granuloma re-grew but then regressed and stabilized during 3 years of uncomplicated pamidronate treatment. His hyperphosphatasemia transiently diminished, but all bone turnover markers, especially those of apposition, remained elevated. Two years after pamidronate therapy stopped, bone mineral density (BMD) Z-scores reached +9.1 and +5.8 in the lumbar spine and hip, respectively, and iliac crest histopathology confirmed rapid bone remodeling. Serum multiplex biomarker profiling was striking for low sclerostin. Mutation analysis was negative for activation of lipoprotein receptor-related protein 4 (LRP4), LRP5, or TGFß1, and for defective sclerostin (SOST), osteoprotegerin (OPG), RANKL, RANK, SQSTM1, or sFRP1. Microarray showed no notable copy number variation. Studies of his nonconsanguineous parents were unremarkable. The etiology and pathogenesis of this unique syndrome are unknown.


Assuntos
Remodelação Óssea , Osteoporose , Osteosclerose , Criança , Difosfonatos/administração & dosagem , Humanos , Masculino , Osteoporose/sangue , Osteoporose/diagnóstico por imagem , Osteoporose/fisiopatologia , Osteosclerose/sangue , Osteosclerose/diagnóstico por imagem , Osteosclerose/fisiopatologia , Pamidronato , Radiografia , Esqueleto , Síndrome
13.
Clin Endocrinol (Oxf) ; 80(1): 85-91, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23745601

RESUMO

INTRODUCTION: Obesity has been associated with a positive influence on bone mass. This is thought to be due to a mechanical load exerted on the skeleton, together with various hormones and adipocytokines that control appetite and weight, such as leptin, some of which directly affect bone mass. However, there are conflicting reports of the association between fat mass and bone mass in children. Animal studies demonstrate increased bone mass where there is impaired central leptin signalling. Hypothalamic damage can cause abnormal central leptin action, which contributes to the development of obesity. OBJECTIVE: The objective of this study was to investigate the relationship between body composition and bone mass in hypothalamic and simple childhood obesity, in conjunction with the effect of the adipocytokines, leptin and adiponectin. DESIGN: This was a cross-sectional study of three groups of children, those with hypothalamic obesity (HO), those with congenital hypopituitarism (CH) and those with simple obesity (SO). RESULTS: A total of 65 children (HO = 26 [11 males], CH = 17 [eight males] and SO = 22 [15 males]) had body composition assessed using dual-energy X-ray absorptiometry together with measurement of serum leptin and adiponectin. No significant differences were seen in bone mass once bone density (BMD) was adjusted for differences in body size between groups. Significantly elevated levels of leptin and adiponectin were seen in the HO group compared with the SO group (P < 0·01, P < 0·05, respectively). CONCLUSION: Adiposity is associated with increased bone mass; however, this relationship is complex. Despite the presence of hyperleptinaemia, increased bone mass in the HO group was not seen. This may be due to the effects of other factors such as adiponectin, abnormal hypothalamic signalling, pituitary hormone deficiencies and disruption of normal homoeostatic mechanisms within the hypothalamus.


Assuntos
Composição Corporal/fisiologia , Leptina/metabolismo , Obesidade/metabolismo , Absorciometria de Fóton , Adiposidade/fisiologia , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Hipopituitarismo/metabolismo , Masculino
14.
J Pediatr Endocrinol Metab ; 26(11-12): 1041-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23751384

RESUMO

AIM: Cranial diabetes insipidus (CDI) is rare in infants with no guidelines on its management. We describe the first case series, characterizing the clinical features and treatment challenges. METHOD: Retrospective case note review of infants diagnosed with CDI between April 1992 and February 2011. RESULTS: Nineteen infants (52% male) were identified. Eight were born preterm. Median (range) age at diagnosis was 24 days (5-300); preterm babies were younger at diagnosis (21 vs. 46 days). In 58% (11/19) of infants, hypernatraemia was discovered incidentally. In 37% of cases there was associated midline anomalies, however, only four patients (21%) had absent posterior pituitary signal on a magnetic resonance imaging brain scan. The most frequent (5/19) underlying diagnosis was septo-optic dysplasia. Eight patients had isolated CDI and 11 had multiple pituitary hormone deficiencies. Isolated CDI tended to be more common in preterm, compared to term babies (p=0.11). Des-amino arginine vasopressin (DDAVP) was administered intranasally in eight and orally in 11 infants. Plasma sodium nadir following DDAVP administration was lower following intranasal compared to an oral route of administration (median: 128 vs. 133 mmol/L, p=0.022). No cases resolved on follow-up. CONCLUSIONS: CDI in infants is often diagnosed incidentally. Aetiology, clinical, and imaging features are very variable, with some differences between preterm and term infants. Oral DDAVP appears to be superior to intranasal with less pronounced serum sodium fluctuations.


Assuntos
Diabetes Insípido/terapia , Crânio/patologia , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Imageamento por Ressonância Magnética , Estudos Retrospectivos
15.
Hum Mol Genet ; 21(22): 4904-9, 2012 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-22875837

RESUMO

Dysosteosclerosis (DSS) is the form of osteopetrosis distinguished by the presence of skin findings such as red-violet macular atrophy, platyspondyly and metaphyseal osteosclerosis with relative radiolucency of widened diaphyses. At the histopathological level, there is a paucity of osteoclasts when the disease presents. In two patients with DSS, we identified homozygous or compound heterozygous missense mutations in SLC29A3 by whole-exome sequencing. This gene encodes a nucleoside transporter, mutations in which cause histiocytosis-lymphadenopathy plus syndrome, a group of conditions with little or no skeletal involvement. This transporter is essential for lysosomal function in mice. We demonstrate the expression of Slc29a3 in mouse osteoclasts in vivo. In monocytes from patients with DSS, we observed reduced osteoclast differentiation and function (demineralization of calcium surface). Our report highlights the pleomorphic consequences of dysfunction of this nucleoside transporter, and importantly suggests a new mechanism for the control of osteoclast differentiation and function.


Assuntos
Exoma , Mutação , Proteínas de Transporte de Nucleosídeos/genética , Osteopetrose/genética , Osteosclerose/genética , Sequência de Aminoácidos , Animais , Pré-Escolar , Consanguinidade , Feminino , Humanos , Lactente , Camundongos , Dados de Sequência Molecular , Osteopetrose/diagnóstico por imagem , Osteosclerose/diagnóstico por imagem , Radiografia , Alinhamento de Sequência
16.
Arch Dis Child ; 97(11): 952-4, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22913973

RESUMO

BACKGROUND: In response to a resurgence of symptomatic cases of vitamin D deficiency in a high-risk predominantly ethnic minority population, a programme of universal rather than targeted vitamin D supplementation was begun with a public awareness campaign about the importance of vitamin D. OBJECTIVE: To evaluate the effectiveness of this programme in reducing case numbers. METHODS: Cases of symptomatic vitamin D deficiency in children under 5 years resident in a primary care trust catchment area presenting at local hospitals were identified through laboratory records of low vitamin D levels which were cross-checked against medical records to confirm the diagnosis. Comparisons were made of the case incidence rate, level of public knowledge and vitamin supplement uptake rate at the onset of the programme in 2005 and 4 years later. RESULTS: The number of cases of symptomatic vitamin D deficiency in those under 5 years fell by 59% (case incidence rate falling from 120/100 000 to 49/100 000) despite the supplement uptake rate rising only to 17%. Public awareness of vitamin D deficiency rose to near universal levels. CONCLUSIONS: A programme of universal rather than targeted Healthy Start vitamin D supplementation for pregnant and lactating women and young children has led to a substantial decrease in cases of symptomatic vitamin D deficiency in a high-risk population. Supplementation was also started at a younger age than in the national programme. This approach has implications for the delivery of vitamin D supplementation programmes in similar populations.


Assuntos
Suplementos Nutricionais , Assistência Alimentar , Saúde Pública/métodos , Raquitismo/prevenção & controle , Deficiência de Vitamina D/prevenção & controle , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Pré-Escolar , Inglaterra , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Lactação , Gravidez , Avaliação de Programas e Projetos de Saúde , Raquitismo/epidemiologia , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/etnologia
17.
Arch Dis Child ; 97(6): 533-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22447996

RESUMO

Hypercalcaemia is a far less common finding in children than in adults. It may present with characteristic symptoms or may be identified as a coincidental finding in children investigated for a variety of complaints. Assessment of hypercalcaemia requires an understanding of the normal physiological regulation of plasma calcium by the combined actions of parathyroid hormone, 1,25-dihydroxyvitamin D(3) and the calcium sensing receptor. Hypercalcaemia will usually require treatment using a number of different modalities but occasionally it can be due to a benign asymptomatic condition that requires no intervention. This article presents a logical approach to the investigation and subsequent management of this condition.


Assuntos
Cálcio/metabolismo , Hipercalcemia/etiologia , Hormônio Paratireóideo/fisiologia , Adulto , Cálcio/sangue , Criança , Homeostase , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/fisiopatologia , Hipercalcemia/terapia , Hormônio Paratireóideo/sangue , Vitamina D/análogos & derivados , Vitamina D/fisiologia
19.
J Pediatr ; 156(3): 450-5, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19880140

RESUMO

OBJECTIVE: To examine the functional and skeletal effects of 30 months of steroid treatment in boys with Duchenne muscular dystrophy. STUDY DESIGN: Lumbar spine (L(2)L(4)) and subcranial dual energy X-ray absorptiometry scanning was performed on 25 boys (mean age 7.4 years) at baseline and after 30 months of steroid treatment. RESULTS: At baseline, L(2)L(4) bone mineral content (BMC) was significantly low for projected bone area although appropriate for reduced lean body mass (LBM). Subcranial bone area for height and subcranial BMC for area and LBM were all significantly reduced. After 30 months of steroid therapy there was a significant increase in subcranial bone area for height but a significant reduction of subcranial BMC for area. At the lumbar spine there were no significant changes in bone area but small increases in L(2)L(4) BMC both for bone area and LBM. CONCLUSION: At baseline reduced mechanical load from diminished muscle function results in narrow light bones more noticeable in the subcranial region than the lumbar spine. Increases observed in subcranial bone area at 30 months suggest a gradual adaptation to increased gravitational load whereas at the spine there were no apparent detrimental effects on bone after 30 months of steroid therapy.


Assuntos
Densidade Óssea , Osso e Ossos/patologia , Glucocorticoides/uso terapêutico , Distrofia Muscular de Duchenne/tratamento farmacológico , Prednisolona/uso terapêutico , Absorciometria de Fóton , Índice de Massa Corporal , Criança , Glucocorticoides/efeitos adversos , Humanos , Vértebras Lombares , Masculino , Força Muscular , Distrofia Muscular de Duchenne/patologia , Distrofia Muscular de Duchenne/fisiopatologia , Prednisolona/efeitos adversos , Caminhada
20.
Eur J Endocrinol ; 159 Suppl 1: S33-9, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18772270

RESUMO

Osteoporosis is being increasingly recognised in paediatric practice as a consequence of several factors. These include the increasing complexity of chronic conditions and the associated treatments managed by paediatricians. In addition, the improved care provided to children with chronic illness has led to many of them living long enough to develop osteoporosis. The availability of methods to assess bone density in children as a surrogate marker of bone strength and the possibility of medical treatment to increase bone density have also resulted in an increased awareness of groups of children who may be at risk of osteoporosis. This article reviews the current definition of osteoporosis in children, aetiological factors and the evidence for effective treatment.


Assuntos
Osteoporose/diagnóstico , Osteoporose/terapia , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Osso e Ossos/anormalidades , Criança , Citocinas/metabolismo , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Fraturas Ósseas/etiologia , Glucocorticoides/efeitos adversos , Humanos , Mediadores da Inflamação/metabolismo , Limitação da Mobilidade , Osteoporose/complicações , Osteoporose/etiologia , Prevenção Primária/métodos , Puberdade Tardia/complicações , Terminologia como Assunto , Magreza/complicações
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