Valoración nutricional mediante curvas de crecimiento de la OMS y las clasificaciones de Gómez / Waterlow. Estudio de prevalencia. Cuenca-2015

Objetivo: Determinar la prevalencia de malnutrición mediante las curvas de crecimiento (OMS) y de desnutrición según la clasificación Gómez/Waterlow; establecer ventajas y desventajas del empleo de ambos sistemas de clasificación. Métodos: Estudio de prevalencia realizado en el Subcentro de Salud Sinincay, con una población de 737 niños/as registrados en la matriz de vigilancia alimentaria y nutricional (SIVAN) durante Enero-Junio 2015, que identificó la malnutrición infantil mediante el uso de criterios OMS y de desnutrición según Gómez/ Waterlow. Resultados: De 47.6% niñas y 52.4% niños, divididos en lactantes (35.8%) y preescolares (64.2%), se determinó la prevalencia de malnutrición según las tablas de OMS (bajo peso 4.6%, bajo peso severo 0.4%, talla baja 20.8%, talla baja severa 2.8%, sobrepeso 0.5% y obesidad 0.3%) y de desnutrición según la clasificación de Gómez/Waterlow (desnutrición aguda 0.1%, desnutrición crónica agudizada 0.1% y enanismo nutricional 30.3%). No hubo variaciones estadísticamente significativas (p>0.05) entre sexo/grupo etario y ambos sistemas de clasificación, pero si existió variación estadística (p<0.05) entre la relación de la OMS y la clasificación Gómez/Waterlow. Conclusiones: El método de Gómez/Waterlow permitió detectar mayor número de casos de desnutrición mientras que las curvas OMS, detectaron sobrepeso y obesidad

The use of fluorescence in situ hybridization in the diagnosis of hidden mosaicism: apropos of three cases of sex chromosome anomalies

FISH has been used as a complement to classical cytogenetics in the detection of mosaicism in sex chromosome anomalies. The aim of this study is to describe three cases in which the final diagnosis could only be achieved by FISH. Case 1 was an 8-year-old 46,XY girl with normal female genitalia referred to our service because of short stature. FISH analysis of lymphocytes with probes for the X and Y centromeres identified a 45,X/46,X,idic(Y) constitution, and established the diagnosis of Turner syndrome. Case 2 was a 21-month-old 46,XY boy with genital ambiguity (penile hypospadias, right testis, and left streak gonad). FISH analysis of lymphocytes and buccal smear identified a 45,X/46,XY karyotype, leading to diagnosis of mixed gonadal dysgenesis. Case 3 was a 47,XYY 19-year-old boy with delayed neuromotor development, learning disabilities, psychological problems, tall stature, small testes, elevated gonadotropins, and azoospermia. FISH analysis of lymphocytes and buccal smear identified a 47,XYY/48,XXYY constitution. Cases 1 and 2 illustrate the phenotypic variability of the 45,X/46,XY mosaicism, and the importance of detection of the 45,X cell line for proper management and follow-up. In case 3, abnormal gonadal function could be explained by the 48,XXYY cell line. The use of FISH in clinical practice is particularly relevant when classical cytogenetic analysis yields normal or uncertain results in patients with features of sex chromosome aneuploidy. Arq Bras Endocrinol Metab. 2012;56(8):545-51

Síndrome metabólica e baixa estatura em adultos da região metropolitana de São Paulo (SP, Brasil)

A desnutrição pregressa, expressa pela baixa estatura, pode ser fator de risco para síndrome metabólica (SM). O objetivo deste estudo foi verificar a prevalência de SM e sua relação com a baixa estatura, possível resultante de desnutrição crônica na infância, em população adulta. Foi feito um estudo transversal em população adulta, com idades entre 20 e 64 anos, residente em município da região metropolitana da cidade de São Paulo (SP). A amostra foi composta por 287 indivíduos, sendo 214 (74,6%) do sexo feminino e 75 (25,4%) do sexo masculino. Foram obtidos dados antropométricos, por meio de exame físico, dados bioquímicos (glicemia, colesterol total e frações, triglicérides) pela coleta de sangue em jejum e dados clínicos. A prevalência padronizada por sexo e idade para a síndrome metabólica foi de 34,0% e para a baixa estatura, 29,0%. A análise por regressão logística múltipla demonstrou associação entre a baixa estatura e a SM, ajustada por sexo, idade, escolaridade, renda, tabagismo, etilismo, atividade física, antecedentes familiares de doenças coronarianas, hipertensão arterial, diabetes e índice de massa corporal. Neste estudo, encontrou-se associação entre SM e baixa estatura, sugerindo que a desnutrição pregressa seja fator de risco para essa morbidade.

A novel COL1A1 gene-splicing mutation (c. 1875+1G > C) in a Brazilian patient with osteogenesis imperfecta

Osteogenesis imperfecta is a heterogeneous genetic disorder characterized by bone fragility and deformity, recurrent fractures, blue sclera, short stature, and dentinogenesis imperfecta. Most cases are caused by mutations in COL1A1 and COL1A2 genes. We present a novel splicing mutation in the COL1A1 gene (c. 1875+ 1G>C) in a 16-year-old Brazilian boy diagnosed as a type III osteogenesis imperfecta patient. This splicing mutation and its association with clinical phenotypes will be submitted to the reference database of COL1A1 mutations, which has no other description of this mutation.

A Previously Undescribed Syndrome Combining Fibular Agenesis/Hypoplasia, Oligodactylous Clubfeet, Anonychia/Ungual Hypoplasia, and Other Defects

We describe an apparently new genetic syndrome in six members of a family living in a remote area in Northeastern Brazil. This syndrome comprises: short stature Clue to a marked decrease in the length of the lower limbs (predominantly mesomelic with fibular agenesis/marked hypoplasia), grossly malformed/deformed clubfeet with severe oligodactyly, tipper limbs with acromial dimples and variable motion limitation of the forearms and/or hands, severe nail hypoplasia/anonychia sometimes associated with mild brachydactyly and occasionally with pre-axial polydactyly. This syndrome is apparently distinct from the syndrome of brachydactyly-ectrodactyly with fibular aplasia or hypoplasia (OMIM 113310), the syndrome of fibular aplasia or hypoplasia, femoral bowing and poly-, syn-, and oligodactyly (OMIM 228930), and from other previously described conditions exhibiting fibular agenesis/hvpoplasia. (C) 2008 Wiley-Liss, Inc.

Usefulness of MLPA in the detection of SHOX deletions

SHOX haploinsufficiency causes a wide spectrum of short stature phenotypes, such as Leri-Weill dyschondrosteosis (LWD) and disproportionate short stature (DSS). SHOX deletions are responsible for approximately two thirds of isolated haploinsufficiency; therefore, it is important to determine the most appropriate methodology for detection of gene deletion. In this study, three methodologies for the detection of SHOX deletions were compared: the fluorescence in situ hybridization (FISH), microsatellite analysis and multiplex ligation-dependent probe amplification (MLPA). Forty-four patients (8 LWD and 36 DSS) were analyzed. The cosmid LLNOYCO3`M`34F5 was used as a probe for the FISH analysis and microsatellite analysis were performed using three intragenic microsatellite markers. MLPA was performed using commercial kits. Twelve patients (8 LWD and 4 DSS) had deletions in SHOX area detected by MLPA and 2 patients generated discordant results with the other methodologies. In the first case, the deletion was not detected by FISH. In the second case, both FISH and microsatellite analyses were unable to identify the intragenic deletion. In conclusion, MLPA was more sensitive, less expensive and less laborious; therefore, it should be used as the initial molecular method for the detection of SHOX gene deletion. (C) 2010 Elsevier Masson SAS. All rights reserved.

A novel STAT5B mutation causing GH insensitivity syndrome associated with hyperprolactinemia and immune dysfunction in two male siblings

Background: GH insensitivity (GHI) syndrome caused by STAT5B mutations was recently reported, and it is characterized by extreme short stature and immune dysfunction. Treatment with recombinant human IGF1 (rhIGF1) is approved for patients with GHI, but the growth response to this therapy in patients with STAT5B mutations has not been reported. Objectives: To report the clinical features, molecular findings, and the short-term growth response to rhIGF1 therapy in patients with STAT5B mutation. Subjects and methods: Hormonal and immunological evaluations were performed in two male siblings with GHI associated with atopic eczema, interstitial lung disease, and thrombocytopenic purpura. STAT5B genes were directly sequenced. The younger sibling was treated with rhIGF1 at a dose of 110 mu g/kg BID. Results: Both siblings had laboratory findings compatible with GHI associated with hyperprolactinemia. Lymphopenia and reduced number of natural killer cells without immunoglobulin abnormalities were observed. STAT5B sequence revealed a homozygous frameshift mutation (p.L142fsX161) in both siblings. The younger sibling (9.9 years of age) was treated with rhIGF1 at appropriate dosage, and he did not present any significant change in his growth velocity (from 2.3 to 3.0 cm/year after 1.5 years of therapy). The presence of a chronic illness could possibly be responsible for the poor result of rhIGF1 treatment. Further studies in patients with STAT5B defects are necessary to define the response to rhIGF1 treatment in this disorder. Conclusion: GHI associated with immune dysfunction, especially interstitial lung disease, and hyperprolactinemia is strongly suggestive of a mutation in STAT5B in both sexes.

A novel bioassay for human somatogenic activity in serum samples supports the clinical reliability of immunoassays

OBJECTIVE Because there is discordance between different immunoassay values for serum hGH, and because clinical state may not correlate with immunoreactive hGH, we have developed an assay to accurately measure serum hGH somatogenic bioactivity. The results of this assay were compared with the Elegance two-site ELISA assay across 135 patient samples in a variety of clinical states. DESIGN The somatogenic assay was based on stable expression of hGH receptor in the murine BaF line, allowing these cells to proliferate in response to hGH. To eliminate interference by other growth factors in serum, we created a specific antagonist of the hGH receptor (similar to Trovert or Pegvisomant) which allowed us to obtain a true measure of hGH somatogenic activity by subtraction of the activity in the presence of the antagonist. The assay was carried out in microtiter plates over 24 h, with oxidation of a chromogenic tetrazolium salt (MTT) as the endpoint. PATIENTS These encompassed a number of different clinical conditions related to short stature, including idiopathic short stature, neurosecretory dysfunction and renal failure, as well as obese patients on dietary restriction and normal volunteers. MEASUREMENTS In addition to the colourimetric (MTT) response to hGH, we measured free hGH by stripping out GHBP-bound hGH using beads coupled to a monoclonal antibody to the GHBP (GH binding protein). All samples were measured in both bioassay and ELISA assay. RESULTS This bioassay was sensitive (5 mU/l or 2 mug/l) and precise, and not subject to interference by the GHBP. There was a good correlation (r = 0.95) between bioactivity and immunoactivity across clinical states. There was, however, an increased bioactivity during secretory peaks (over 25 mU/l), which has been reported previously for the Nb2 bioassay. Free hGH did not correlate with clinical state. CONCLUSIONS Because the results of the Elegance ELISA and the bioassay correlate well, even though there is greater bioactivity at higher hormone concentrations, it is evident that an appropriate immunoassay is able to act as a reliable indicator for clinical assessment. In those rare cases where bio-inactive GH exists, our bioassay should provide an appropriate means to demonstrate this.

Heritability of adult body height: A comparative study of twin cohorts in eight countries

A major component of variation in body height is due to genetic differences, but environmental factors have a substantial contributory effect. In this study we aimed to analyse whether the genetic architecture of body height varies between affluent western societies. We analysed twin data from eight countries comprising 30,111 complete twin pairs by using the univariate genetic model of the Mx statistical package. Body height and zygosity were self-reported in seven populations and measured directly in one population. We found that there was substantial variation in mean body height between countries; body height was least in Italy (177 cm in men and 163 cm in women) and greatest in the Netherlands (184 cm and 171 cm, respectively). In men there was no corresponding variation in heritability of body height, heritability estimates ranging from 0.87 to 0.93 in populations under an additive genes/unique environment (AE) model. Among women the heritability estimates were generally lower than among men with greater variation between countries, ranging from 0.68 to 0.84 when an additive genes/shared environment/unique environment (ACE) model was used. In four populations where an AE model fit equally well or better, heritability ranged from 0.89 to 0.93. This difference between the sexes was mainly due to the effect of the shared environmental component of variance, which appears to be more important among women than among men in our study populations. Our results indicate that, in general, there are only minor differences in the genetic architecture of height between affluent Caucasian populations, especially among men.

Mammography equipment design: impact on radiographers’ practice

Objectives - Identify radiographers’ postures during frequent mammography procedures related to the mammography equipment and patient characteristics. Methods - A postural task analysis was performed using images acquired during the simulation of mammography positioning procedures. Simulations included craniocaudal/(CC) and mediolateral-oblique/(MLO) positioning in three different settings: radiographers and patients with similar statures, radiographers smaller than the patients and radiographers taller than the patients. Measurements of postural angles were performed by two raters using adequate software and classified according to the European Standard EN1005-4:2005 + A1:2008. Results - The simulations revealed that the most awkward posture in mammography is during the positioning of MLO projection in short-stature patients. Postures identified as causing work-related musculoskeletal disorder (WRMSD) risk were neck extension, arms elevated and the back stooped, presenting angles of 87.2, 118.6 and 63.6, respectively. If radiographers were taller than patients, then the trunk and arm postures were not acceptable. Conclusions - Working in a mammography room leads to awkward postures that can have an impact on radiographers’ health, namely WRMSDs. The results in this study showed that there are non-acceptable postures associated with frequent working procedures in mammography. MLO is the most demanding procedure for radiographer postures and may be related to WRMSDs. Mammography devices should be redesigned considering adjustability for radiographers. Main Messages: • Mammography constraints for radiographers in mammography procedures have not been well studied. • Performing mammography leads to awkward postures that can impact radiographers’ health. • MLO, the most demanding procedure for radiographers, is possibly related to WRMSDs.

Achondroplasia and Down’s Syndrome – Case Report of a Rare Association

The association of achondroplasia and Down’s syndrome is very rare and only five cases have been reported in the literature so far. These two genetic alterations have overlapping features such as short stature, developmental delay or hypotonia that complicate management and follow up. We report the case of a girl that is unique since she was born from a mother with achondroplasia and a healthy father. Achondroplasia was dominantly inherited from the mother but at birth she had features of Down’s syndrome as well, confirmed later by kariotype. We review her evolution regarding physical health, cognitive problems and adaptive behavior during her eight years of life. To our knowledge this is the first report of the combination of both disorders in which the achondroplasia was inherited and not a “de novo” mutation. We address the problems resulting from the additional burden of having two disorders, and how they can be improved, aiming to help others in the future to deal with these cases.

Inibidores da Aromatase em Adolescentes do Sexo Masculino com Baixa Estatura Idiopática

Introdução: O efeito dos fármacos inibidores da aromatase (IA) na estatura de jovens do sexo masculino com baixa estatura idiopática (BEI) tem vindo a ser estudado desde que foi evidenciado o papel dos estrogénios na paragem do crescimento linear. Os ensaios clínicos aleatorizados, duplamente cegos, de caso-controlo com letrozol indicam impacto positivo na previsão de estatura final em jovens do sexo masculino com BEI, com ou sem atraso constitucional do crescimento e puberdade. Por persistirem aspetos de segurança a requerer melhor estudo, a sua utilização terapêutica continua a ser off label. Objetivos: Tendo em vista a implementação de um ensaio clínico sobre a terapêutica com IA em jovens do sexo masculino com BEI procedeu-se a uma revisão sistemática da literatura, na qual se fundamenta a proposta de protocolo apresentada. Métodos: Pesquisa na base de dados eletrónica Medline de revisões sistemáticas, ensaios clínicos alea-torizados controlados e referências bibliográficas dos artigos seleccionados, publicados entre Janeiro de 2001 e Dezembro de 2012. Conclusões: A terapêutica com um IA de terceira geração (letrozol) poderá ser considerada em jovens do sexo masculino com BEI, altura inferior a pelo menos −2,0 SDS para a idade ou previsão de altura final pelo menos 2,0 SDS abaixo da estatura média parental, desde que já tenha sido iniciada a puberdade e a idade óssea seja inferior a 14 anos. Os principais aspectos de segurança ainda sob discussão na literatura referem-se a potenciais efeitos a nível ósseo. A utilização de medicamentos off-label deve obedecer a critérios estritos de prescrição e seguimento das crianças, de forma a minimizar os riscos e obter resultados fiáveis e comparáveis. Apresenta-se proposta de sistematização de monitorização clínica, imagiológica e laboratorial, bem como critérios de término ou suspensão da mesma.

Noonan syndrome: a clinical and genetic study of 31 patients

Noonan syndrome is a multiple congenital anomaly syndrome, inherited in an autosomal dominant pattern. We studied 31 patients (18 males and 13 females) affected by this disorder regarding their clinical and genetic characteristics. The most frequent clinical findings were short stature (71%); craniofacial dysmorphisms, especially hypertelorism, ptosis, downslanting of the palpebral fissures; short or webbed neck (87%); cardiac anomalies (65%), and fetal pads in fingers and toes (70%). After studying the probands' first-degree relatives, we made the diagnosis of Noonan syndrome in more than one family member in three families. Therefore, the majority of our cases were sporadic.

Oral manifestations of Albright hereditary Osteodystrophy: a case report

Albright hereditary osteodystrophy is a hereditary metabolic disorder of dominant autosomal etiology that is commonly characterized by short stature, round face, small metacarpus and metatarsus, mental retardation, osteoporosis, subcutaneous calcification, variable hypocalcemia, and hyperphosphatemia. In this study, we report a clinical case of a 17-year-old woman with Albright hereditary osteodystrophy, and we discuss her clinical, radiographic, and laboratory test characteristics together with the oral manifestations, and we correlate them with the characteristics found in the literature. We also discuss the odontological management of treatment of related periodontal disease and planning for corrections of related malocclusions.