Diabetes mellitus in childhood: an emerging condition in the 21st century.

The International Diabetes Federation (IDF-2015) estimates the existence of 30,900 children under 15 years old with type 1 diabetes mellitus (DM1) in Brazil, and an increase of 3.0% per year is expected. This review focused on meta-analysis and pediatric diabetes update articles in order to draw attention to the need of planning coping strategies to support this serious public health problem in coming years. DM1 is considered an immuno-mediated disease with a complex transmission influenced by genetic and environmental factors responsible for a gradual destruction of the insulin producing pancreatic beta cells. Seroconversion to DM1-associated autoantibodies and abnormalities in metabolic tests that assess insulin secretion and glucose tolerance can be used as predictive criteria of beta cells functional reserve and the onset of the clinical disease. Symptomatic DM1 treatment is complex and the maintenance of good metabolic control is still the only effective strategy for preserving beta cell function. Disease duration and hyperglycemia are both risk factors for the onset of chronic vascular complications that negatively affect the quality of life and survival of these patients. In this regard, health teams must be trained to provide the best possible information on pediatric diabetes, through continuing education programs focused on enabling these young people and their families to diabetes self-management.

Diabetes mellitus in childhood: an emerging condition in the 21st century / Diabetes mellitus na infância: uma condição emergente no século 21

Summary The International Diabetes Federation (IDF-2015) estimates the existence of 30,900 children under 15 years old with type 1 diabetes mellitus (DM1) in Brazil, and an increase of 3.0% per year is expected. This review focused on meta-analysis and pediatric diabetes update articles in order to draw attention to the need of planning coping strategies to support this serious public health problem in coming years. DM1 is considered an immuno-mediated disease with a complex transmission influenced by genetic and environmental factors responsible for a gradual destruction of the insulin producing pancreatic beta cells. Seroconversion to DM1-associated autoantibodies and abnormalities in metabolic tests that assess insulin secretion and glucose tolerance can be used as predictive criteria of beta cells functional reserve and the onset of the clinical disease. Symptomatic DM1 treatment is complex and the maintenance of good metabolic control is still the only effective strategy for preserving beta cell function. Disease duration and hyperglycemia are both risk factors for the onset of chronic vascular complications that negatively affect the quality of life and survival of these patients. In this regard, health teams must be trained to provide the best possible information on pediatric diabetes, through continuing education programs focused on enabling these young people and their families to diabetes self-management.

Resumo A Federação Internacional de Diabetes (IDF-2015) estima a existência no Brasil de 30.900 menores de 15 anos portadores de diabetes mellitus tipo 1 (DM1), com previsão de aumento de 3,0% ao ano. Esta revisão buscou artigos de metanálise e atualização em diabetes infantil com o objetivo de alertar para a necessidade do planejamento de estratégias de enfrentamento deste que tende a ser um sério problema de saúde pública para os próximos anos. O DM1 é considerado uma doença imunomediada de transmissão complexa, influenciada por fatores genéticos e ambientais determinantes da destruição gradual das células beta pancreáticas produtoras de insulina. A positividade sorológica dos autoanticorpos associados ao DM1 e a alteração de testes metabólicos que avaliam a secreção de insulina e o estado glicêmico podem ser utilizados como critérios de previsão da reserva funcional de células beta e do início clínico da doença. O tratamento do DM1 sintomático é complexo, e a manutenção do bom controle metabólico é ainda a única estratégia efetiva de preservação das células beta ainda funcionantes. Tempo de duração da doença e hiperglicemia são fatores de risco para a instalação das complicações vasculares crônicas, que afetam negativamente a qualidade de vida e a sobrevida desses indivíduos. Torna-se necessária a formação de equipes de saúde preparadas para fornecer a melhor informação possível em diabetes infantil, através de programas de educação continuada, com potencial de capacitar esses jovens e suas famílias para o autocuidado.

Tireoidite autoimune na criança e no adolescente / Autoimmune thyroiditis in children and adolescents

Objetivo: Revisão da literatura sobre a tireoidite de Hashimoto no universo das doenças autoimunes em crianças e adolescentes. Fontes: MEDLINE, utilizando os termos tireoidite, doença de Hashimoto, genética da autoimunidade tireoidiana. Resumo: Doenças tireoidianas autoimunes são doenças endócrinas frequentes da criança e do adolescente. Genes como antígeno humano leucocitário (HLA), antígeno-4 associado ao linfócito T citotóxico (CTLA-4), a proteína tirosina-fosfatase 22 (PTPN22) e os genes específicos da glândula tireoide, como o receptor do TSH (TSHR) e tireoglobulina (Tg) afetam a resposta imunológica da tireoide. A tireoidite autoimune pode apresentar funções tireoidianas desde eutireoidismo até hipotireoidismo evidente, além de um quadro inicial, transitório, de hipertireoidismo e tem sido associada a doenças autoimunes como diabetes, doenças reumáticas, doença celíaca. Função tiroidiana e associações com outras doenças autoimunes são destacados...

Production and partial characterization of serine and metallo peptidases secreted by Aspergillus fumigatus Fresenius in submerged and solid state fermentation

Enzyme production varies in different fermentation systems. Enzyme expression in different fermentation systems yields important information for improving our understanding of enzymatic production induction. Comparative studies between solid-state fermentation (SSF) using agro-industrial waste wheat bran and submerged fermentation (SmF) using synthetic media were carried out to determinate the best parameters for peptidase production by the fungus Aspergillus fumigatus Fresen. Variables tested include: the concentration of carbon and protein nitrogen sources, the size of the inoculum, the pH of the media, temperature, and the length of the fermentation process. The best peptidase production during SSF was obtained after 96 hours using wheat bran at 30 ºC with an inoculum of 1 x 10(6) spores and yielded 1500 active units (UµmL). The best peptidase production using SmF was obtained after periods of 72 and 96 hours of fermentation in media containing 0.5% and 0.25% of casein, respectively, at a pH of 6.0 and at 30 ºC and yielded 40 UµmL. We also found examples of catabolite repression of peptidase production under SmF conditions. Biochemical characterization of the peptidases produced by both fermentative processes showed optimum activity at pH 8.0 and 50 ºC, and also showed that their proteolytic activity is modulated by surfactants. The enzymatic inhibition profile using phenylmethylsulfonyl fluoride (PMSF) in SmF and SSF indicated that both fermentative processes produced a serine peptidase. Additionally, the inhibitory effect of the ethylene-diaminetetraacetic acid (EDTA) chelating agent on the peptidase produced by SmF indicated that this fermentative process also produced a metallopeptidase.

A novel DAX1/NR0B1 mutation in a patient with adrenal hypoplasia congenita and hypogonadotropic hypogonadism / Uma nova mutação DAX1/NR0B1 em um paciente com hipoplasia adrenal congênita e hipogonadismo hipogonadotrófico

We report a case of adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH) due to a novel DAX1 mutation. A 19-month-old boy with hyperpigmentation and failure to thrive came to our service for investigation. Three brothers of the patient had died due to adrenal failure, and a maternal cousin had adrenal insufficiency. Adrenoleukodystrophy was excluded. MRI showed normal pituitary and hypothalamus. Plasma hormone evaluation revealed high ACTH (up to 2,790 pg/mL), and low levels of androstenedione, DHEA-S, 11-deoxycortisol, and cortisol. At 14 years of age the patient was still prepubescent, his weight was 43.6 kg (SDS: -0.87) and his height was 161 cm (SDS: -0.36), with normal body proportions. In the GnRH test, basal and maximum values of LH and FSH were respectively 0.6/2.1 and < 1.0/< 1.0 U/L. Molecular investigation identified a novel mutation that consists of a deletion of codon 372 (AAC; asparagine) in exon 1 of DAX1. This mutation was not found in a study of 200 alleles from normal individuals. Prediction site analysis indicated that this alteration, located in the DAX1 ligand-binding domain, may damage DAX1 protein. We hypothesize that the novel (p.Asp372del) DAX1 mutation might be able to cause a disruption of DAX1 function, and is probably involved in the development of AHC and HH in this patient. Arq Bras Endocrinol Metab. 2012;56(8):496-500.

Relatamos um caso de hipoplasia adrenal congênita (HAC) e hipogonadismo hipogonadotrófico (HH) causado por uma nova mutação do gene DAX1. Paciente do sexo masculino com 19 meses de idade, hiperpigmentação e desenvolvimento inadequado foi encaminhado ao nosso serviço. Antecedente familiar de três irmãos falecidos por falência da adrenal, e um primo materno portador de insuficiência adrenal. Excluída a hipótese de adrenoleucodistrofia. A RM demonstrou hipófise e hipotálamo normais. Os níveis de hormônios plasmáticos mostraram alta concentração de ACTH (até 2.790 pg/mL) e baixos níveis de androstenediona, DHEA-S, 11-deoxicortisol e cortisol. Aos 14 anos de idade, o paciente ainda era pré-púbere, com peso de 43,6 kg (SDS: -0,87) e altura de 161 cm (SDS: -0,36), proporcionado. O teste do GnRH mostrou níveis basais e máximos de LH e FSH, respectivamente, iguais a 0,6/2,1 e < 1,0/< 1,0 U/L. A análise molecular identificou uma nova mutação que consiste da deleção do códon 372 (AAC; asparagina) no éxon 1 do gene DAX1. Essa mutação não foi encontrada em 200 alelos de indivíduos normais. A análise no site PredictProtein indicou que essa alteração, localizada no domínio de ligação do DAX1, pode danificar a proteína. Nossa hipótese é que essa nova mutação (p.Asp372del) do gene DAX1 pode levar a uma alteração na função da proteína DAX1 e está provavelmente envolvida no desenvolvimento da HAC e HH nesse paciente. Arq Bras Endocrinol Metab. 2012;56(8):496-500.

A novel DAX1/NR0B1 mutation in a patient with adrenal hypoplasia congenita and hypogonadotropic hypogonadism.

We report a case of adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH) due to a novel DAX1 mutation. A 19-month-old boy with hyperpigmentation and failure to thrive came to our service for investigation. Three brothers of the patient had died due to adrenal failure, and a maternal cousin had adrenal insufficiency. Adrenoleukodystrophy was excluded. MRI showed normal pituitary and hypothalamus. Plasma hormone evaluation revealed high ACTH (up to 2,790 pg/mL), and low levels of androstenedione, DHEA-S, 11-deoxycortisol, and cortisol. At 14 years of age the patient was still prepubescent, his weight was 43.6 kg (SDS: -0.87) and his height was 161 cm (SDS: -0.36), with normal body proportions. In the GnRH test, basal and maximum values of LH and FSH were respectively 0.6/2.1 and < 1.0/< 1.0 U/L. Molecular investigation identified a novel mutation that consists of a deletion of codon 372 (AAC; asparagine) in exon 1 of DAX1. This mutation was not found in a study of 200 alleles from normal individuals. Prediction site analysis indicated that this alteration, located in the DAX1 ligand-binding domain, may damage DAX1 protein. We hypothesize that the novel (p.Asp372del) DAX1 mutation might be able to cause a disruption of DAX1 function, and is probably involved in the development of AHC and HH in this patient.

Síndrome metabólica em crianças e adolescentes: dúvidas na terminologia, mas não nos riscos cardiometabólicos / Metabolic syndrome in children and adolescents: doubts about terminology but not about cardiometabolic risks

A síndrome metabólica (SM) tem gerado enormes controvérsias, a iniciar-se pela terminologia. O próprio autor que sugeriu o termo, Gerald Reaven, recomenda que não o utilizemos, porque, como a síndrome é um apanhado de alterações metabólicas e três dessas alterações podem defini-la, fica sempre difícil saber-se a que conjunto de alterações estamos nos referindo quando conotamos o termo SM. Em crianças, a complicação é ainda maior, já que se fazem diferentes adaptações aos critérios propostos para adultos. De qualquer forma, independentemente da terminologia, os riscos cardiovasculares são bem estabelecidos e fica cada vez mais claro que as crianças, já em tenra idade, podem começar a ter alterações metabólicas preditivas de problemas mais sérios futuramente. Assim, o papel do endocrinologista pediátrico e do pediatra geral é de investigar essas crianças, especialmente se portadoras de sobrepeso ou obesidade, para detectar precocemente e intervir em condições que podem ser prevenidas na vida adulta. Essa é uma nova visão de uma abordagem pediátrica preventiva de problemas que, usualmente, só são diagnosticados em vida adulta. Nesta revisão, abordamos os aspectos de definição, epidemiologia, fisiopatologia e de complicações da SM em crianças e adolescentes.

Metabolic syndrome (MS) has been a condition involved in considerable controversy, starting with the terminology. Gerald Reaven himself, the author who proposed the term MS, advised against the use of this terminology because the definition implies in at least three metabolic alterations, and it is never clear to which group of alterations we are referring to when we say that a patient has MS. In children, the problem is even more complicated, since there are many different adaptations to the criteria used in adults. On the other hand, independent of the terminology, cardiovascular risks are well-established and it is very clear that even children may present metabolic disturbances which predict future metabolic problems. The role of the pediatric endocrinologist or the general pediatrician is to investigate, especially in overweight/obese children, conditions that if treated early, may prevent future complications that today, unfortunately, are being diagnosed only in adult life. In this review, we discuss problems on the definition, epidemiology, pathophysiology, and complications of MS in children and adolescents.

Novel mutation in MCT8 gene in a Brazilian boy with thyroid hormone resistance and severe neurologic abnormalities.

MCT8 is a cellular transporter of thyroid hormones important in their action and metabolization. We report a male patient with the novel inactivating mutation 630insG in the coding region in exon 1 of MCT8. He was characterized clinically by severe neurologic impairment (initially with global hypotonia, later evolving with generalized hypertonia), normal growth during infancy, reduced weight gain, and absence of typical signs and symptoms of hypothyroidism, while the laboratory evaluation disclosed elevated T3, low total and free T4, and mildly elevated TSH serum levels. Treatment with levothyroxine improved thyroid hormone profile but was not able to alter the clinical picture of the patient. These data reinforce the concept that the role of MCT8 is tissue-dependent: while neurons are highly dependent on MCT8, bone tissue, adipose tissue, muscle, and liver are less dependent on MCT8 and, therefore, may suffer the consequences of the exposition to high serum T3 levels.

Novel mutation in MCT8 gene in a Brazilian boy with thyroid hormone resistance and severe neurologic abnormalities / Mutação nova do gene MCT8 em menino Brasileiro com resistência ao hormônio tireioidiano e neuropatia grave

O MCT8 é um transportador celular de hormônios tireoidianos, importante para sua ação e metabolização. Relatamos o caso de um menino com a nova mutação inativadora 630insG no éxon 1 do MCT8. O paciente caracterizou-se por grave comprometimento neurológico (inicialmente com hipotonia global, evoluindo com hipertonia generalizada), crescimento normal nos dois primeiros anos de vida, reduzido ganho ponderal e ausência dos sinais e sintomas típicos de hipotireoidismo. A sua avaliação sérica revelou elevação do T3, redução do T4 total e livre e TSH levemente aumentado. O tratamento com levotiroxina melhorou o perfil hormonal tireoidiano, mas não modificou o quadro clínico do paciente. Esses dados reforçam o conceito de que o papel do MCT8 é tecido-dependente: enquanto os neurônios são altamente dependentes do MCT8, o osso, o tecido adiposo, o músculo e o fígado são menos dependentes do MCT8 e, portanto, podem sofrer as consequências da exposição a níveis séricos elevados de T3.

MCT8 is a cellular transporter of thyroid hormones important in their action and metabolization. We report a male patient with the novel inactivating mutation 630insG in the coding region in exon 1 of MCT8. He was characterized clinically by severe neurologic impairment (initially with global hypotonia, later evolving with generalized hypertonia), normal growth during infancy, reduced weight gain, and absence of typical signs and symptoms of hypothyroidism, while the laboratory evaluation disclosed elevated T3, low total and free T4, and mildly elevated TSH serum levels. Treatment with levothyroxine improved thyroid hormone profile but was not able to alter the clinical picture of the patient. These data reinforce the concept that the role of MCT8 is tissue-dependent: while neurons are highly dependent on MCT8, bone tissue, adipose tissue, muscle, and liver are less dependent on MCT8 and, therefore, may suffer the consequences of the exposition to high serum T3 levels.

[Metabolic syndrome in children and adolescents: doubts about terminology but not about cardiometabolic risks]. / Síndrome metabólica em crianças e adolescentes: dúvidas na terminologia, mas não nos riscos cardiometabólicos.

Metabolic syndrome (MS) has been a condition involved in considerable controversy, starting with the terminology. Gerald Reaven himself, the author who proposed the term MS, advised against the use of this terminology because the definition implies in at least three metabolic alterations, and it is never clear to which group of alterations we are referring to when we say that a patient has MS. In children, the problem is even more complicated, since there are many different adaptations to the criteria used in adults. On the other hand, independent of the terminology, cardiovascular risks are well-established and it is very clear that even children may present metabolic disturbances which predict future metabolic problems. The role of the pediatric endocrinologist or the general pediatrician is to investigate, especially in overweight/obese children, conditions that if treated early, may prevent future complications that today, unfortunately, are being diagnosed only in adult life. In this review, we discuss problems on the definition, epidemiology, pathophysiology, and complications of MS in children and adolescents.

Controle do apetite: mecanismos metabólicos e cognitivos: [revisão] / Appetite control: metabolic and cognitive mechanisms: [review]

Os mecanismos de controle do apetite têm sido estudados focando principalmente as funções hipotalâmicas, regulando o aspecto metabólico da alimentação. A principal preocupação do organismo é manter um equilíbrio energético e, dentro dessaproposta, genes foram selecionados que condicionavam um armazenamento energético, para fazer frente às situações de carência alimentar. Poucosestudos se dedicaram, nos últimos 10 anos, às integrações do hipotálamo com outros centros superiores. Quando os períodos de fome e de carência alimentar cessam em um estilo de vida moderna, este organismo se vê frente a sistemas poupadores, que passam a propiciar um grande armazenamentoenergético, sob a forma de depósitos de gordura, e explode uma verdadeira “pandemia” de obesidade. Os sistemas de controle do apetite estão muito maisvoltados para o armazenamento energético do que para a perda de peso. Todos sabemos das dificuldades de perder peso e como o “cérebro cognitivo” vence o “cérebro metabólico”. O desejo de comer, os estímulos olfatórios, visuais, de lembrança e de recompensa passam por centros superiores, em regiões de córtex órbito-frontal, núcleo acumbens, pálido ventral, dentre numerosas outrasestruturas. Um pouco desta integração será discutida nesta revisão.

The mechanisms that control the appetite have been studied mainly focusing on the hypothalamic functions,which regulates the metabolic aspects of feeding. The main goal of the organism is to keep the energeticbalance and, on this purpose, genes have been selected to allow storage of fuel to face food deprivation. In thelast 10 years, few studies have focused the integration between the hypothalamus and cortical centers. Ina modern era where food deprivation does not occur unless for economic reasons, the organism with its thrifty genes and phenotypes, accumulate energy in the form of fat and an explosion of obesity ensues. We allknow the difficulties to lose weight and how the “cognitive brain” surpasses the “metabolic brain”. The desire to eat, the olfactory, visual, and reward stimulus travel through superior regions of the central nervous system, such as accumbens, ventral pallidus nuclei, among others. A little bit of this integration will be discussed in this review.

[Search of prostatic tissue in 46,XX congenital adrenal hyperplasia]. / Pesquisa de tecido prostático em pacientes 46,XX portadoras da forma clássica de hiperplasia congênita das suprarrenais.

OBJECTIVES: To describe the presence of prostatic tissue in 46,XX patients with the classical form of congenital adrenal hyperplasia (CAH); to evaluate the sensitivity and specificity of prostatic specific antigen (PSA) measured in congenital adrenal hyperplasia patients with regard to the detection of prostatic tissue in pelvic MRI. METHODS: We studied 52 children and adolescents, 32 with the classical form of congenital adrenal hyperplasia, 10 boys and 10 girls without CAH. Pelvic MRI was performed in all patients to detect prostatic tissue. Prostate specific antigen, testosterone and dihydrotestosterone were measured in all patients. We used Receiver Operating Characteristic Curve for PSA discrimination capacity. RESULTS: Five girls with congenital adrenal hyperplasia showed image of prostatic tissue on pelvic MRI. Prostate specific antigen showed sensitivity and specificity of 100% and 88.9%, respectively, taking 0.1 ng/mL as the cutoff level. CONCLUSIONS: The incidence of prostatic tissue in 46,XX patients with the classical form of congenital adrenal hyperplasia was 15.6%. PSA demonstrated to be a good marker of prostatic tissue in these patients and should be used to screen patients to be submitted to image studies.

Pesquisa de tecido prostático em pacientes 46, XX portadoras da forma clássica de hiperplasia congênita das suprarrenais / Search of prostatic tissue in 46, XX congenital adrenal hyperplasia

OBJETIVOS: Verificar a ocorrência de tecido prostático em pacientes portadoras da forma clássica de hiperplasia congênita das suprarrenais, com cariótipo 46,XX e analisar a sensibilidade e a especificidade do antígeno prostático específico (PSA) das pacientes com hiperplasia congênita das suprarrenais em relação à detecção de tecido prostático na ressonância magnética (RNM) de região pélvica. MÉTODOS: Foram estudadas 52 crianças e adolescentes, sendo 32 meninas portadoras da forma clássica de hiperplasia congênita das suprarrenais, 10 meninas e 10 meninos sem hiperplasia congênita das suprarrenais. A RNM da região pélvica e a coleta de PSA, diidrotestosterona e testosterona foram realizadas em todos os pacientes. Para analisar a capacidade de discriminação do antígeno prostático-específico, foi utilizada a curva ROC (receiver operating characteristic curve). RESULTADOS: Cinco das 32 pacientes portadoras de hiperplasia congênita das suprarrenais apresentaram tecido prostático na RNM de região pélvica. Para concentração de antígeno prostático-específico de 0,1 ng/mL, obteve-se sensibilidade de 100 por cento e especificidade de 88,9 por cento para a detecção de tecido prostático. CONCLUSÕES: A ocorrência de tecido prostático nas pacientes portadoras de hiperplasia congênita das suprarrenais estudadas foi de 15,6 por cento. O antígeno prostático-específico mostrou ser valioso marcador de tecido prostático nestas pacientes.

OBJECTIVES: To describe the presence of prostatic tissue in 46,XX patients with the classical form of congenital adrenal hyperplasia (CAH); to evaluate the sensitivity and specificity of prostatic specific antigen (PSA) measured in congenital adrenal hyperplasia patients with regard to the detection of prostatic tissue in pelvic MRI. METHODS: We studied 52 children and adolescents, 32 with the classical form of congenital adrenal hyperplasia, 10 boys and 10 girls without CAH. Pelvic MRI was performed in all patients to detect prostatic tissue. Prostate specific antigen, testosterone and dihydrotestosterone were measured in all patients. We used Receiver Operating Characteristic Curve for PSA discrimination capacity. RESULTS: Five girls with congenital adrenal hyperplasia showed image of prostatic tissue on pelvic MRI. Prostate specific antigen showed sensitivity and specificity of 100 percent and 88.9 percent, respectively, taking 0.1 ng/mL as the cutoff level. CONCLUSIONS: The incidence of prostatic tissue in 46,XX patients with the classical form of congenital adrenal hyperplasia was 15.6 percent. PSA demonstrated to be a good marker of prostatic tissue in these patients and should be used to screen patients to be submitted to image studies.

Raquitismos e metabolismo ósseo / Rickets and bone metabolism / Raquitismos y metabolismo ósseo

Objetivo: atualizar o conhecimento do metabolismo ósseo e da fisiopatogenia, diagnóstico e tratamento dos raquitismos. Fontes pesquisadas:artigos localizados na base MEDLINE publicados entre 1997 e 2007, com as palavras chave “deficiência de vitamina D”, “raquitismo”, e “metabolismoósseo”, além de outros artigos relevantes publicados antes, e as publicações da American Society for Bone and Mineral Research entre 2003e 2008. Síntese dos dados: os conhecimentos relativos ao metabolismo ósseo ampliaram-se, destacando o receptor-sensor de cálcio (RSCa),fundamental no controle da secreção do PTH e da calciúria, e o FGF-23 (fator de crescimento dos fibroblastos-23), importante no controle da fosfatemia através da inibição do co-transportadorde sódio e fosfato tipo II (NPT-II) no túbulo proximal, além de inibir a 1α-hidroxilase e a formação da vitamina D ativa (calcitriol). Foi elucidado o sistema RANKL-RANK-OPG na atividadeosteoclástica. A homeostase do cálcio e fósforo no osso depende da ação integrada do calcitriol, PTH, RSCa e FGF-23. Os distúrbios dessa homeostasepodem causar raquitismo, caracterizadopela inadequada mineralização da placa de crescimento. A deficiência da vitamina D ainda constitui a principal causa, em especial nas populaçõesem desenvolvimento. Em crianças eadolescentes com doenças crônicas o raquitismo pode decorrer de deficiência da vitamina D ou de alterações no seu metabolismo. Novas etiologiasgenéticas de raquitismo hipofosfatêmico foram descritas, relacionadas às alterações da secreção ou ação do FGF-23, ou da ação do NPT-II. Conclusões:o conhecimento da fisiologia óssea pelopediatra permite que o raquitismo seja adequadamente suspeitado e investigado nas crianças com crescimento deficiente ou deformidades e naquelas com doenças crônicas.

Objective: up-to-date the knowledge about bone mineral metabolism and the physiopathology, diagnosis and treatment of rickets. Data source: articles published between 1997-2007 were selected from MEDLINE. Relevant articles published previously to this period and publications from “The American Society for Bone and Mineral Research” from 2003 to 2008 were also examined. Data synthesis: the knowledge about bone mineral physiology has been changed with emphasis on the calcium sensing-receptor (CaSR), that acts to regulate the PTH secretion and the calciuria, and on the FGF-23 (fibroblast growth factor-23), that controls phosphatemiainhibiting the sodium-phosphate co-transporter type II (NPT-II) on proximal tubule, and that also reduces the 1α-hydroxylase activity and the formation of active vitamin D (calcitriol). The role of RANKL-RANK-OPG system on osteoclasts was clarified. The calcium and phosphorus homeostasis depends on the integrated action of calcitriol, PTH,CaSR and FGF-23. Disturbances affecting this homeostasis may cause rickets, characterized by inadequatemineralization of the growth plate. Vitamin D deficiency is still considered an important cause of rickets in Africa, Asia and in populational groupsfrom other countries. Children and adolescents with chronic diseases may have rickets due to deficiencyof vitamin D or to alterations of its metabolism. New etiologies of hypophosphatemic genetic ricketshave been described related to disturbances affecting the secretion or the action of FGF-23 or the actionof NPT-II. Conclusions: the knowledge of bone mineral physiology by pediatricians allows that rickets be adequately suspected and investigatedin children with deficient growth or deformities or with chronic diseases.

Objetivo: actualizar el conocimiento del metabolismo óseo y de la fisiopatogenia, diagnostico y tratamiento de los raquitismos. Fuentes pesquisadas:artículos localIzados en la base de datos MEDLINE publicados entre 1997 y 2007, utilizando las palabras claves “deficiencia de vitamina D”,“raquitismo”, y “metabolismo óseo”, además de otros artículos importantes publicados antes, y las publicaciones de la American Society for Bone andMineral Research entre 2003 y 2008. Síntesis de los datos: los conocimientos relativos al metabolismo óseo se ampliaron, destacando el del receptor-sensor de calcio (RSCa), fundamental en el control de la secreción de PTH y de calciuria, y el FGF-23 (factorde crecimiento de los fibroblastos-23), importante en el control de la fosfatemia a través de su acción renal. Fue elucidado el sistema RANKL-RANKOPGen la actividad osteoclastica. La homeostasis del calcio y fósforo en el hueso depende de la acción integrada del calcitriol, PTH, RSCa y FGF-23. Losdisturbios de esa homeostasis pueden causar raquitismo, caracterizado por la mineralización inadecuada de la placa de crecimiento. La deficiencia devitamina D todavía constituye la causa principal, en especial en las poblaciones en desarrollo. En niños y adolescentes con enfermedades crónicas el raquitismopuede decorrer de la deficiencia de vitamina D o de alteraciones en su metabolismo. Nuevas etiologías genéticas del raquitismo hipofosfatemicofueron descritas, relacionadas a las alteraciones de la secreción o acción del FGF-23, o de la acción del NPT-II. Conclusiones: el conocimiento de la fisiología ósea por el pediatra permite que el raquitismo sea adecuadamente sospechado e investigado en losniños con crecimiento deficiente o deformedades e en aquellos con enfermedades crónicas.