RESUMEN

BACKGROUND: Ectopic calcification is inappropriate biomineralization of soft tissues occurring due to genetic or acquired causes of hyperphosphataemia and rarely in normophosphataemic individuals. Tumoral Calcinosis (TC) is a rare metabolic bone disorder commonly presenting in childhood and adolescence with periarticular extra-capsular calcinosis. Three subtypes of TC have been recognised: primary hyperphosphataemic familial TC (HFTC), primary normophosphataemic familial TC and secondary TC most commonly seen in chronic renal failure. In the absence of established treatment, management is challenging due to variable success rates with medical therapies and recurrence following surgery. AIM: We outline the successful treatment approaches in four children with TC (2 normophosphatemic TC, 2 HFTC) aged 2.5-10 years at initial presentation. CASES: Patient 1 (P1) presented at 10 years with a painless lump behind the right knee, P2 with swelling of the right knee anteriorly at 9 years, P3 and P4 with pain and swelling over the right elbow at 5 and 2.5 years respectively. All patients were of Black African-Caribbean origin and were previously reported to be fit and well with no family history of TC. RESULTS: P1, P2 had normophosphataemic TC and P3, P4 had HFTC with genetically confirmed GALNT3 mutation. All four patients had initial surgical resection with TC confirmed on histology. P1 had complete surgical resection with no recurrence at 27 months post-operatively. P2 had significant overgrowth of the tumour following surgery and was subsequently successfully managed with 25 % topical sodium metabisulphite (total duration of 8 months with a 4 month gap during which there was recurrence). P3 had post-surgical recurrence of TC on the right elbow and a new lesion on left elbow which resolved with oral acetazolamide monotherapy (15-20 mg/kg/day). P4 had recurrence of right elbow lesion following surgery and developed an extensive new hip lesion on sevelamer therapy which resolved completely with additional acetazolamide therapy (18-33 mg/kg/day). Acetazolamide was well tolerated with normal growth for 5 years in P3 and 6.5 years in P4 and no recurrence of lesions. CONCLUSION: The frequent post-surgical recurrence in TC and successful medical therapy on the other hand indicates that medical management as first line therapy should be adopted. Monotherapies with topical 25 % sodium metabisulphite in normophosphataemic and oral acetazolamide in HFTC are effective treatment strategies which are well tolerated.

Asunto(s)

Calcinosis , Hiperfosfatemia , Niño , Adolescente , Humanos , Acetazolamida/uso terapéutico , Sulfitos , Hiperfosfatemia/genética , Calcinosis/genética

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INTRODUCTION: X-linked hypophosphataemia (XLH) is conventionally managed with oral phosphate and active vitamin D analogues. OBJECTIVES: To evaluate long term treatment response by assessing biochemical disease activity [serum alkaline phosphatase (ALP)], radiological rickets severity score (RSS), growth and morbidity in patients with XLH on conventional therapy and assess the correlation between serum ALP and RSS. METHODS: XLH patients from 3 UK tertiary centres with ≥3 radiographs one year apart were included. Data was collected retrospectively. The RSS was assessed from routine hand and knee radiographs and ALP z scores were calculated using age-specific reference data. RESULTS: Thirty-eight (male = 12) patients met the inclusion criteria. The mean ± SD knee, wrist and total RSS at baseline (median age 1.2 years) were 2.0 ± 1.2, 1.9 ± 1.2 and 3.6 ± 1.3 respectively; and at the most recent clinic visit (median age 9.0 years, range 3.3-18.9) were 1.6 ± 1.0, 1.0 ± 1.0 and 2.5 ± 1.5 respectively. The mean ± SD serum ALP z scores at baseline and the most recent visit were 4.2 ± 2.3 and 4.0 ± 3.3. Median height SDS at baseline and most recent visit were -1.2 and -2.1 (p = 0.05). Dental abscess, craniosynostosis, limb deformity requiring orthopaedic intervention and nephrocalcinosis were present in 31.5%, 7.9%, 31.6% and 42.1% of the cohort respectively. There was no statistically significant (p > 0.05) correlation between ALP z scores and knee (r = 0.07) or total (r = 0.12) RSS. CONCLUSIONS: Conventional therapy was not effective in significantly improving biochemical and radiological features of disease. The lack of association between serum ALP and rickets severity on radiographs limits the value of ALP as the sole indicator of rickets activity in patients receiving conventional therapy.

Asunto(s)

Raquitismo Hipofosfatémico Familiar , Raquitismo , Adolescente , Niño , Preescolar , Mano , Humanos , Lactante , Articulación de la Rodilla , Masculino , Fosfatos , Estudios Retrospectivos , Raquitismo/tratamiento farmacológico

RESUMEN

BACKGROUND: Vitamin D deficiency (VDD) affects the health and wellbeing of millions worldwide. In high latitude countries such as the United Kingdom (UK), severe complications disproportionally affect ethnic minority groups. OBJECTIVE: To develop a decision-analytic model to estimate the cost effectiveness of population strategies to prevent VDD. METHODS: An individual-level simulation model was used to compare: (I) wheat flour fortification; (II) supplementation of at-risk groups; and (III) combined flour fortification and supplementation; with (IV) a 'no additional intervention' scenario, reflecting the current Vitamin D policy in the UK. We simulated the whole population over 90 years. Data from national nutrition surveys were used to estimate the risk of deficiency under the alternative scenarios. Costs incurred by the health care sector, the government, local authorities, and the general public were considered. Results were expressed as total cost and effect of each strategy, and as the cost per 'prevented case of VDD' and the 'cost per Quality Adjusted Life Year (QALY)'. RESULTS: Wheat flour fortification was cost saving as its costs were more than offset by the cost savings from preventing VDD. The combination of supplementation and fortification was cost effective (£9.5 per QALY gained). The model estimated that wheat flour fortification alone would result in 25% fewer cases of VDD, while the combined strategy would reduce the number of cases by a further 8%. CONCLUSION: There is a strong economic case for fortifying wheat flour with Vitamin D, alone or in combination with targeted vitamin D3 supplementation.

Asunto(s)

Harina , Alimentos Fortificados , Triticum , Deficiencia de Vitamina D/economía , Deficiencia de Vitamina D/prevención & control , Vitamina D , Adolescente , Adulto , Anciano , Niño , Colecalciferol/administración & dosificación , Colecalciferol/economía , Análisis Costo-Beneficio , Inglaterra/epidemiología , Etnicidad/estadística & datos numéricos , Femenino , Harina/economía , Alimentos Fortificados/economía , Humanos , Masculino , Persona de Mediana Edad , Grupos Minoritarios/estadística & datos numéricos , Vitamina D/administración & dosificación , Vitamina D/economía , Deficiencia de Vitamina D/dietoterapia , Deficiencia de Vitamina D/epidemiología , Gales/epidemiología , Adulto Joven

RESUMEN

AIM: To estimate the proportion of type 2 diabetes mellitus and abnormal glucose homeostasis in childhood obesity and assess the predictive role of HbA1c as a diagnostic marker compared with oral glucose tolerance testing (OGTT). METHODS: A retrospective study in a tertiary paediatric hospital. Data were collected on all overweight or obese children who underwent routine OGTT between 2012 and 2016. Ethnicity, anthropometry, comorbidities and other risk factors associated with diabetes were recorded systematically. Fasting venous glucose, insulin and HbA1c values, along with 120-min venous glucose were recorded. Receiver operating characteristic (ROC) curve analysis was performed to derive optimum thresholds of HbA1c for detection of type 2 diabetes, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Predictive HbA1c thresholds for the detection of abnormal glucose homeostasis in children with obesity were calculated. RESULTS: Of 156 children, 13 (8%, 10 female, 10 Asian) had type 2 diabetes, 95 (61%) had normal glucose tolerance, 18 (12%) had isolated IFG, 19 (12%) had isolated IGT, and another 11 (7%) had both IFG and IGT. The proportion of abnormal glucose homeostasis was 39%. ROC curve analysis demonstrated that HbA1c ≥ 42 mmol/mol (6.0%) predicted type 2 diabetes (specificity 95%, sensitivity 85%) but performed moderately for IFG (specificity 46%, sensitivity 78%) and IGT (specificity 78%, sensitivity 55%). CONCLUSION: Despite HbA1c being a less-sensitive diagnostic tool compared with OGTT for children with IFG and IGT, it is reliable in detecting type 2 diabetes in asymptomatic children with obesity, instead of the labour- and cost-intensive OGTT.

Asunto(s)

Glucemia/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Intolerancia a la Glucosa/diagnóstico , Hemoglobina Glucada/metabolismo , Obesidad Infantil/metabolismo , Estado Prediabético/diagnóstico , Adolescente , Niño , Diabetes Mellitus Tipo 2/metabolismo , Ayuno/metabolismo , Femenino , Intolerancia a la Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Humanos , Resistencia a la Insulina , Masculino , Tamizaje Masivo , Estado Prediabético/metabolismo , Estudios Retrospectivos , Sensibilidad y Especificidad , Reino Unido

RESUMEN

OBJECTIVES: Hypophosphataemic rickets (HR) is usually secondary to renal phosphate wasting but may occur secondary to reduced intake or absorption of phosphate. We describe a series of cases of HR associated with the use of Neocate®, an amino-acid based formula (AAF). METHODS: A retrospective review of cases with HR associated with AAF use presenting to centres across the United Kingdom. RESULTS: 10 cases were identified, over a 9 month period, all associated with Neocate® use. The age at presentation was 5 months to 3 years. The majority (8/10) were born prematurely. Gastro oesophageal reflux disease (6/10) was the most frequent indication for AAF use. Radiologically apparent rickets was observed after a median of 8 months (range 3-15 months) of exclusive Neocate® feed. The majority (7/10) were diagnosed on the basis of incidental findings on radiographs: rickets (6/10) or fracture with osteopenia (5/10). All patients had typical biochemical features of HR with low serum phosphate, high alkaline phosphatase, normal serum calcium and 25 hydroxyvitamin D. However, in all cases the tubular reabsorption of phosphate (TRP) was ≥96%. Phosphate supplementation resulted in normalisation of serum phosphate within 1-16 weeks, and levels remained normal only after Neocate® cessation. In patients with sufficient follow up duration (4/10), normalisation of phosphate and radiological healing of rickets was noted after 6 months (range: 6-8 months) following discontinuation of Neocate®. CONCLUSION: The presence of a normal TRP and resolution of hypophosphataemia and rickets following discontinuation of Neocate® indicates this is a reversible cause likely mediated by poor phosphate absorption. Close biochemical surveillance is recommended for children on Neocate®, especially in those with gastrointestinal co-morbidities, with consideration of a change in feed or phosphate supplementation in affected children.

Asunto(s)

Aminoácidos/efectos adversos , Carbohidratos/efectos adversos , Grasas de la Dieta/efectos adversos , Fosfatos , Raquitismo Hipofosfatémico , Huesos/diagnóstico por imagen , Huesos/patología , Preescolar , Femenino , Humanos , Lactante , Fórmulas Infantiles , Masculino , Fosfatos/sangre , Fosfatos/metabolismo , Fosfatos/uso terapéutico , Estudios Retrospectivos

RESUMEN

Oral glucocorticoids (GC) preserve muscle strength and prolong walking in boys with Duchenne muscular dystrophy (DMD). Although vertebral fractures have been reported in boys taking GC, fracture rates for different GC regimes have not been investigated. The aim of this pragmatic longitudinal study was to compare growth, body mass, bone mineral density (BMD), vertebral fractures (VF) and ambulatory status in boys with DMD on daily (DAILY) or intermittent (INTERMITTENT), oral GC regimens. A convenience sample of 50 DMD boys from two centres was included in the study; 25 boys each were on the DAILY or INTERMITTENT regimen. Size adjusted lumbar spine BMD (LS BMAD), total body less head BMD (TBLH), by DXA and distal forearm bone densities by pQCT, GC exposure, VF assessment and ambulatory status were analysed at three time points; baseline, 1 and 2 years. At baseline, there were no differences in age, GC duration or any bone parameters. However, DAILY boys were shorter (height SDS DAILY = -1.4(0.9); INTERMITTENT = -0.8(1.0), p = 0.04) with higher BMI (BMI SDS DAILY = 1.5(0.9); INTERMITTENT = 0.8(1.0), p = 0.01). Over 2 years, DAILY boys got progressively shorter (delta height SDS DAILY = -0.9(1.1); INTERMITTENT = +0.1(0.6), p < 0.001). At their 2 year assessment, 5 DAILY and 10 INTERMITTENT boys were non-ambulant. DAILY boys had more VFs than INTERMITTENT boys (10 versus 2; χ2 p = 0.008). BMAD SDS remained unchanged between groups. TBLH and radius BMD declined significantly but the rate of loss was not different. In conclusion, there was a trend for more boys on daily GCs to remain ambulant but at the cost of more VFs, greater adiposity and markedly diminished growth. In contrast, boys on intermittent GCs had fewer vertebral fractures but there was a trend for more boys to loose independent ambulation.

Asunto(s)

Huesos/patología , Glucocorticoides/uso terapéutico , Crecimiento y Desarrollo , Distrofia Muscular de Duchenne/tratamiento farmacológico , Caminata , Administración Oral , Densidad Ósea/efectos de los fármacos , Huesos/efectos de los fármacos , Huesos/fisiopatología , Niño , Esquema de Medicación , Estudios de Seguimiento , Fracturas Óseas/complicaciones , Fracturas Óseas/patología , Fracturas Óseas/fisiopatología , Glucocorticoides/farmacología , Crecimiento y Desarrollo/efectos de los fármacos , Humanos , Masculino , Distrofia Muscular de Duchenne/complicaciones , Distrofia Muscular de Duchenne/fisiopatología

RESUMEN

Cartilage-hair hypoplasia (CHH) is an autosomal recessive chondrodysplasia characterized by short-stature, sparse hair and impaired cellular immunity. We describe a young girl who was diagnosed with CHH based on the findings of recurrent infections, short stature with metaphyseal chondrodysplasia, and a confirmed bi-allelic RMRP gene mutation. At 13 years, the patient developed an Epstein-Barr virus (EBV)-driven lymphoproliferative disorder involving the lung, which responded partially to chemotherapy. Simultaneously, she developed multiple indurated plaques involving her face, which had histological findings of granulomatous inflammation and EBV-associated low-grade lymphomatoid granulomatosis. The patient received a matched unrelated peripheral blood stem cell transplant at 15 years of age, and her immunological parameters and skin lesions improved. Lymphomatoid forms of granulomatosis and cutaneous EBV-associated malignancies have not been described previously in CHH. This case highlights the possibility of EBV-associated cutaneous malignancy in CHH.

Asunto(s)

Cabello/anomalías , Enfermedad de Hirschsprung/complicaciones , Síndromes de Inmunodeficiencia/complicaciones , Neoplasias Pulmonares/complicaciones , Pulmón/patología , Granulomatosis Linfomatoide/complicaciones , Osteocondrodisplasias/congénito , Neoplasias Cutáneas/complicaciones , Adolescente , Femenino , Herpesvirus Humano 4/aislamiento & purificación , Enfermedad de Hirschsprung/terapia , Humanos , Síndromes de Inmunodeficiencia/terapia , Pulmón/virología , Neoplasias Pulmonares/patología , Granulomatosis Linfomatoide/patología , Osteocondrodisplasias/complicaciones , Osteocondrodisplasias/terapia , Enfermedades de Inmunodeficiencia Primaria , Trasplante de Células Madre

RESUMEN

Osteogenesis Imperfecta (OI) is a condition of bone fragility and can present with early onset scoliosis that can cause respiratory complications in later life. The fear of instrumenting the spine in OI is the possibility of fracture either on primary insertion or subsequent lengthening. Magnetically controlled growing rods were inserted to control a scoliosis in a 6-year old with OI type IV. Fixation was obtained using pedicle screws proximally and distally with sublaminar bands around the ribs proximally. These rods have been remotely lengthened on multiple occasions over a 2-year period. This has controlled the scoliosis whilst also allowing the spine to grow. There are no complications to report. This case reports the use of magnetically controlled growth rods used to manage early onset scoliosis in OI. Frequent lengthening, achieving small increases in length on every occasion protects against the risk of fracture during the lengthening procedure.

RESUMEN

Vertebral fracture assessment (VFA) by DXA is an accepted tool in adults. However, its use in children has not been assessed. The aim of this study was to evaluate DXA VFA and morphometric analysis (MXA) using a GE Lunar iDXA bone densitometer against spinal radiographic assessment (RA) for the identification of vertebral fractures in children. Spine RA and VFA (T3-L5) were acquired on the same day in 80 children. Forty children considered high risk for fracture by their metabolic bone specialist were referred for spinal RA. Another 40 children were recruited as part of a prospective fracture study and were considered low risk for vertebral fracture. Agreement between RA and VFA was assessed by an expert paediatric radiologist and two paediatricians with expertise in bone pathology. Agreement between RA and MXA was assessed by an expert paediatric radiologist, two clinical scientists and an experienced paediatric radiographer. Vertebrae were ranked as normal, mild, moderate or severe if they had <10%, 11-25%, 26-50% and >50% deformity, respectively. Levels of agreement were calculated using the Cohen kappa score. Evaluating the data from all readable vertebrae, 121 mild, 44 moderate and 16 severe vertebral fractures were identified; with 26, 8, and 5 subjects having at least one mild, moderate or severe fracture, respectively. Depending on rater, 92.8-94.8% of the vertebrae were evaluable by RA. In contrast, 98.4% were evaluable by VFA and only 83.6% were evaluable by MXA. Moderate agreement was found between raters for RA [kappa 0.526-0.592], and VFA [kappa 0.601-0.658] and between RA and VFA [kappa 0.630-0.687]. In contrast, only slight agreement was noted between raters for MXA [kappa 0.361-0.406] and between VFA and MXA [kappa 0.137-0.325]. Agreement substantially improved if the deformities were dichotomised as normal or mild versus moderate or severe [kappa 0.826-0.834]. For the detection of moderate and/or severe fractures the sensitivities & specificities were 81.3% & 99.3%, and 62.5% & 99.2% for VFA and MXA, respectively. This study demonstrates that VFA is as good as RA for detecting moderate and severe vertebral fractures. Given the significant radiation dose saving of VFA compared with RA, VFA is recommended as a diagnostic tool for the assessment of moderate or severe vertebral fracture in children.

Asunto(s)

Absorciometría de Fotón , Fracturas de la Columna Vertebral/diagnóstico por imagen , Adolescente , Niño , Relación Dosis-Respuesta en la Radiación , Humanos , Radiografía , Estándares de Referencia , Fracturas de la Columna Vertebral/patología

RESUMEN

PurposeTo describe the prevalence and natural history of retinopathy in a cohort of children and young people with type 1 diabetes attending a tertiary hospital diabetes clinic.MethodsWe analysed retinopathy screening data from 2008 to 2010 on all eligible children using the 'Twinkle' diabetes database and the regional retinal screening database.ResultsA total of 88% (149/169) of eligible children were screened in 2008, median age 14 years, 52% male. The prevalence of retinopathy was 19.5% (30/149). All children had background retinopathy grade R1. There was significant difference in median (range) duration of diabetes, 7.7 years (0.6-13.7) vs 5 years (0.2-12.5) (P<0.001) and median (range) HbA1C, 9.1% (7.2-14) vs 8.6% (5.6-13.1) (P=0.02), between the groups with and without retinopathy. At 2- years follow-up, 12/30 (40%) had unchanged retinopathy grade R1, 10/30 (33.3%) showed resolution of changes (R0), 1/30 progressed to maculopathy, and 7/30 had no follow-up data. Median (range) HbA1C in 2008 and 2010 for the groups with stable vs resolved changes was similar, 9.1% (7.2-14.0) and 9.2% (7-14.0) vs 9.5% (7.8-14.0) and 9.2% (8.7-14.0). Of the 119 without retinopathy in 2008, 27 (22.5%) had developed retinopathy within 2 years, including 1 with pre-proliferative retinopathy and 1 with maculopathy. There was no significant difference in HbA1c between those who progressed to retinopathy (8.7% (7.1-13.1)) (8.7% (7.1-13.1)), and those who did not (8.6% (6.3-12.2)).ConclusionsPrevalence of background retinopathy in our cohort was comparable to the previously published reports, with higher HbA1c and longer duration of diabetes being significant risk factors. On short-term follow-up, Grade 1 retinopathy is likely to resolve in a third of patients and remain unchanged in just over a third.

Asunto(s)

Diabetes Mellitus Tipo 1/epidemiología , Retinopatía Diabética/epidemiología , Adolescente , Glucemia/metabolismo , Niño , Bases de Datos Factuales , Diabetes Mellitus Tipo 1/diagnóstico , Retinopatía Diabética/diagnóstico , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Centros de Atención Terciaria , Factores de Tiempo , Reino Unido/epidemiología

RESUMEN

"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)

Humanos , Femenino , Raquitismo/terapia , Complicaciones del Embarazo/prevención & control , Raquitismo , Raquitismo/diagnóstico , Deficiencia de Vitamina D/complicaciones , Lactancia , Embarazo , Calcio/deficiencia , Salud Pública , Factores de Riesgo

RESUMEN

UNLABELLED: Several established methods are used to size adjust dual-energy X-ray absorptiometry (DXA) measurements in children. However, there is no consensus as to which method is most diagnostically accurate. All size-adjusted bone mineral density (BMD) values were more diagnostically accurate than non-size-adjusted values. The greatest odds ratio was estimated volumetric BMD for vertebral fracture. INTRODUCTION: The size dependence of areal bone density (BMDa) complicates the use of DXA in children with abnormal stature. Despite several size adjustment techniques being proposed, there is no consensus as to the most appropriate size adjustment technique for estimating fracture risk in children. The aim of this study was to establish whether size adjustment techniques improve the diagnostic ability of DXA in a cohort of children with chronic diseases. METHODS: DXA measurements were performed on 450 children, 181 of whom had sustained at least one low trauma fracture. Lumbar spine (L2-L4) and total body less head (TBLH) Z-scores were calculated using different size adjustment techniques, namely BMDa and volumetric BMD for age (bone mineral apparent density (BMAD)); bone mineral content (BMC) and bone area for height; BMC for bone area; BMC for lean mass (adjusted for height); and BMC for bone and body size. RESULTS: Unadjusted L2-L4 and TBLH BMDa were most sensitive but least specific at distinguishing children with fracture. All size adjustments reduced sensitivity but increased post-test probabilities, from a pre-test probability of 40 % to between 58 and 77 %. The greatest odds ratio for fracture was L2-L4 BMAD for a vertebral fracture and TBLH for lean body mass (LBM) (adjusted for height) for a long bone fracture with diagnostic odds ratios of 9.3 (5.8-14.9) and 6.5 (4.1-10.2), respectively. CONCLUSION: All size adjustment techniques improved the predictive ability of DXA. The most accurate method for assessing vertebral fracture was BMAD for age. The most accurate method for assessing long bone fracture was TBLH for LBM adjusted for height.

Asunto(s)

Absorciometría de Fotón/métodos , Densidad Ósea/fisiología , Fracturas Osteoporóticas/diagnóstico , Fracturas de la Columna Vertebral/diagnóstico , Adolescente , Niño , Enfermedad Crónica , Femenino , Humanos , Vértebras Lumbares/fisiopatología , Masculino , Fracturas Osteoporóticas/fisiopatología , Estudios Retrospectivos , Fracturas de la Columna Vertebral/fisiopatología

RESUMEN

The association in young females of long-standing primary hypothyroidism, isosexual precocious pseudopuberty and multicystic enlarged ovaries was first described in 1960 by Van Wyk and Grumbach. Since then, sporadic case reports have contributed to clarifying the key features of this syndrome. The unique elements that lead to this diagnosis are FSH-dominated sexual precocity combined with a delayed bone age in the presence of hypothyroidism. It is important to recognise this syndrome because initiating simple thyroid hormone replacement completely resolves symptoms and hormone abnormalities, avoiding unnecessary investigations for malignancies or surgical intervention. We describe an 8-year-old girl with autoimmune thyroiditis and severe long-standing hypothyroidism presenting with the clinical features of Van Wyk-Grumbach syndrome, a secondary TSH-secreting adenoma and hyperprolactinaemia. In addition, this girl presented with microcytic anaemia, elevated erythrocyte sedimentation rate (ESR) and two unusual features - a newly developed streaky hyperpigmented skin lesion and parathyroid hormone suppression despite vitamin D deficiency. Thyroxine replacement normalised all hormone abnormalities and shrunk the pituitary adenoma within 9 months, but the new skin lesion persisted. We review the literature and explore the pathophysiology of known and new features that give rise to speculation indicating stimulation of the FSH G protein-coupled receptor by excessive TSH, but LH suppression by hyperprolactinaemia.

Asunto(s)

Hipotiroidismo/diagnóstico por imagen , Quistes Ováricos/diagnóstico por imagen , Pubertad Precoz/diagnóstico por imagen , Niño , Diagnóstico Diferencial , Femenino , Humanos , Hipotiroidismo/complicaciones , Quistes Ováricos/complicaciones , Pubertad Precoz/complicaciones , Ultrasonografía

RESUMEN

BACKGROUND: Sodium valproate (VPA) is commonly used to treat epilepsy in children. Renal dysfunction is a rare side eff ect but can present as tubulopathy such as Fanconi syndrome. CASE REPORT: We report on an 8-year-old disabled girl with myoclonic epilepsy who was referred for investigation of recurrent low impact fractures of the distal femur which were initially thought to be caused by her severe immobility. However, she was subsequently found to have hypophosphataemia secondary to Fanconi syndrome due to prolonged VPA use. After VPA withdrawal renal function and serum phosphate levels normalised and X-rays improved dramatically. CONCLUSION: The possibility of drug-induced osteoporosis and fractures should always be considered in disabled children, even in the presence of severe immobility.

Asunto(s)

Niños con Discapacidad , Epilepsias Mioclónicas/tratamiento farmacológico , Síndrome de Fanconi/inducido químicamente , Fracturas del Fémur/inducido químicamente , Ácido Valproico/efectos adversos , Niño , Femenino , Humanos , Ácido Valproico/uso terapéutico

RESUMEN

PURPOSE: The diversity of pediatric dual-energy x-ray absorptiometry (DXA) bone mineral density (BMD) reference databases raises questions as to whether they are interchangeable in their application. This study examined the comparability of BMD Z-scores generated from the largest available Hologic DXA databases, applied on BMD results of a large series of unselected pediatric patients. METHODS: A total of 2027 BMD scans were extracted from Hologic QDR-4500A machines. Age- and sex-specific BMD Z-scores of children aged 8-17 yr, calculated from six Hologic databases, were compared for lumbar spine (LS) and total body (TB). The final dataset included 708 scans (307 of girls). RESULTS: BMD Z-scores calculated from the six databases were highly correlated but differed significantly (P < 0.001) in both scan regions. Interdatabase Z-score differences (boys/girls, respectively) were up to 0.54/0.55 for LS and 1.0/0.83 for TB. These differences also varied significantly among age groups. In girls, the percentage of LS BMD Z-scores of -2 or below ("low BMD for age") varied between 15.4 and 27.9% (P < 0.012). The percentage of TB BMD Z-scores of -2 or below varied similarly in boys (P < 0.009). CONCLUSIONS: Clinically relevant differences in BMD Z-scores exist between the Hologic databases, revealing a significant potential for misdiagnosis. Ideally, Z-scores should be calculated using model-, brand-, and software-specific reference curves for age, sex, and ethnic group. However, our results can be used to estimate converted values. There are other differences in children's bone mass, shape, strength, and body size that are not detected by DXA.

Asunto(s)

Densidad Ósea/fisiología , Bases de Datos Factuales , Gráficos de Crecimiento , Proyectos de Investigación/normas , Absorciometría de Fotón , Adolescente , Determinación de la Edad por el Esqueleto/métodos , Determinación de la Edad por el Esqueleto/normas , Niño , Bases de Datos Factuales/normas , Femenino , Humanos , Vértebras Lumbares/diagnóstico por imagen , Masculino , Valores de Referencia , Estudios Retrospectivos

RESUMEN

Oxcarbazepine (OXC) induces cytochrome CYP3A4 activity, lowering female sex steroid concentrations. To date, similar effects on corticosteroid concentrations have not been reported. The observation of an adolescent boy with Addison's disease requiring high hydrocortisone replacement doses while on OXC for epilepsy led us to investigate effects of OXC on CYP3A4 induction and steroid metabolism. Six young epileptic men on OXC monotherapy and six controls collected 24-h urines and had blood taken for steroid analysis. Accelerated cortisol elimination was confirmed by greater relative 24-h urinary 6-hydroxycortisol/cortisol excretion (4.67 (1.25) µg/day vs controls 2.32 (0.5) µg/day, p=0.001). Patients on OXC had lower serum oestradiol and dehydroepiandrosterone sulphate levels, but only tendencies remained after age adjustment. This study shows that OXC-induced CYP3A4 activity increases cortisol elimination. The effect is small in subjects with healthy adrenals. However, caution is warranted for patients with adrenal failure on high doses of OXC where choosing an alternative anticonvulsant may be advisable.

Asunto(s)

Anticonvulsivantes/farmacología , Carbamazepina/análogos & derivados , Citocromo P-450 CYP3A/biosíntesis , Hidrocortisona/farmacocinética , Enfermedad de Addison/complicaciones , Enfermedad de Addison/tratamiento farmacológico , Enfermedad de Addison/metabolismo , Adolescente , Adulto , Carbamazepina/farmacología , Interacciones Farmacológicas , Inducción Enzimática/efectos de los fármacos , Epilepsia del Lóbulo Temporal/complicaciones , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Epilepsia del Lóbulo Temporal/metabolismo , Humanos , Masculino , Oxcarbazepina , Adulto Joven

Asunto(s)

Desarrollo Óseo/fisiología , Huesos/fisiología , Músculo Esquelético/crecimiento & desarrollo , Músculo Esquelético/fisiología , Caracteres Sexuales , Niño , Femenino , Humanos , Masculino

RESUMEN

INTRODUCTION: When expressed as a percentage of the average result in young adults, bone mineral content lags behind bone length before puberty. Even though this observation has led to speculation about bone fragility in children, such relationships could simply be due to scaling effects when measures with different geometrical dimensions are compared. METHODS: The study population comprised 145 healthy subjects (6-25 years, 94 females). Magnetic resonance imaging and dual-energy X-ray absorptiometry were used to determine femur length, bone mineral content, cortical bone mineral density, cross-sectional bone geometry (bone diameter; cortical thickness; total, cortical and medullary areas; cross-sectional and polar moments of area; bone strength index) and muscle area at the proximal one-third site of the femur. Results were dimensionally scaled by raising two-, three- and four-dimensional variables to the power of 1/2, 1/3 and 1/4, respectively. Sex-differences were also assessed before and after functionally adjusting variables for femur length and weight or muscle size. RESULTS: In prepubertal children, unscaled results expressed as percentages of adult values were lowest for variables with the highest dimensions (e.g., moments of area

Asunto(s)

Desarrollo Óseo/fisiología , Fémur/crecimiento & desarrollo , Desarrollo de Músculos/fisiología , Músculo Esquelético/crecimiento & desarrollo , Adolescente , Adulto , Tamaño Corporal , Peso Corporal , Densidad Ósea , Niño , Estudios Transversales , Femenino , Fémur/anatomía & histología , Fémur/metabolismo , Humanos , Masculino , Músculo Esquelético/anatomía & histología , Factores Sexuales

RESUMEN

AIM: To define the demographics and clinical characteristics of cases presenting with nutritional rickets to paediatric centres in Sydney, Australia. METHODS: Retrospective descriptive study of 126 cases seen from 1993 to 2003 with a diagnosis of vitamin D deficiency and/or confirmed rickets defined by long bone x ray changes. RESULTS: A steady increase was seen in the number of cases per year, with a doubling of cases from 2002 to 2003. Median age of presentation was 15.1 months, with 25% presenting at less than 6 months of age. The most common presenting features were hypocalcaemic seizures (33%) and bowed legs (22%). Males presented at a younger age, with a lower weight SDS, and more often with seizures. The caseload was almost exclusively from recently immigrated children or first generation offspring of immigrant parents, with the region of origin predominantly the Indian subcontinent (37%), Africa (33%), and the Middle East (11%). Seventy nine per cent of the cases were born in Australia. Eleven cases (all aged <7 months) presented atypically with hyperphosphataemia. CONCLUSIONS: This large case series shows that a significant and increasing caseload of vitamin D deficiency remains, even in a developed country with high sunlight hours. Cases mirror recent immigration trends. Since birth or residence in Australia does not appear to be protective, screening of at risk immigrant families should be implemented through public health policies.

Asunto(s)

Raquitismo/epidemiología , Preescolar , Estudios de Cohortes , Femenino , Humanos , Hidroxicolecalciferoles/sangre , Incidencia , Masculino , Nueva Gales del Sur/epidemiología , Hormona Paratiroidea/sangre , Estudios Retrospectivos , Raquitismo/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/epidemiología