Primer reporte en Argentina de variante patógena en DMP1 asociada a raquitismo hipofosfatémico autosómico recesivo / First report in Argentina of a pathogenic DMP1 variant associated with autosomal recessive hypophosphatemic rickets

El raquitismo hipofosfatémico hereditario es una condición genética asociada con una mineralización ósea alterada causada por la deficiencia de fosfato. Produce deformidad esquelética y retraso del crecimiento en la infancia. Se describen diferentes patrones de herencia según el locus involucrado. Dado el solapamiento de los fenotipos y la dificultad en analizar genealogías reducidas, los estudios moleculares son importantes para establecer la causa genética y realizar el abordaje familiar. La forma recesiva del raquitismo hipofosfatémico (ARHR, OMIM #241520) es una condición extremadamente poco frecuente reportada en familias de origen europeo y de Oriente Medio. Las mutaciones con pérdida de función del gen DMP1 (dentin matrix acidic phosphoprotein 1) se asocian al raquitismo hipofosfatémico hereditario tipo 1. En este artículo presentamos el primer reporte de una familia argentina con raquitismo hipofosfatémico hereditario por mutación en DMP1

Hereditary hypophosphatemic rickets is a genetic condition associated with impaired bone mineralization caused by phosphate deficiency. It results in skeletal deformity and growth retardation in early childhood. Different inheritance patterns have been described according to the locus involved. Given the phenotypic overlapping and the difficulty in analyzing reduced genealogies, molecular studies are important to establish the genetic cause and implement a family-centered approach. The autosomal recessive form of hypophosphatemic rickets (ARHR, OMIM 241520) is an extremely rare condition reported in families of European and Middle Eastern descent. Loss-of-function mutations in the DMP1 (dentin matrix acidic phosphoprotein 1) gene are associated with hereditary hypophosphatemic rickets type 1. In this article, we describe the first report of an Argentine family with hereditary hypophosphatemic rickets due to a mutation in the DMP1 gene.

Raquitismo hipofosfatémico familiar ligado al cromosoma X: Reporte de Caso

El Fósforo es regulado por el riñón y el sistema óseo orquestado principalmente por la acción de la parathormona (PTH) y una molécula recientemente descrita como el factor de crecimiento fibroblástico 23 (FGF-23) . Presentamos los casos de dos pacientes madre-hijo con Raquitismo hipofosfatémico ligado al cromosoma X. Se realizó el estudio genético identificándose una mutación en el Gen PHEX: variante patogénica tipo splicing en hemicigosis: mutación previamente descrita como HGMD CS126536. El Raquitismo Hipofosfatémico forma parte de un grupo de tubulopatías caracterizadas hiperfosfaturia. La mutación del gen PHEX con pérdida de función conduce al aumento de FGF-23. PHEX degrada el FGF-23 en fragmentos inactivos, evitando la excreción excesiva de fosfatos y el desarrollo de hipofosfatemia. En un paciente con hipofosfatemia no dependiente de la hormona PTH o de la vitamina D y de presentación familiar debe considerarse el diagnóstico de Raquitismo hipofosfatémico ligado al cromosoma X.

Phosphate is regulated by the kidneys and the osseus system, mainly due to the action of parathyroid hormone (PTH) and a recently described molecule, fibroblast growth factor 23 (FGF-23). We present the cases of two patients, mother and son with X-chromosome linked hypophosphatemic rickets. The genetic study was performed, and a mutation in the PHEX gene was identified, a splicing type pathogenic variant in hemizygosis. This mutation was previously described as HGMD CS126536. Hypophosphatemic rickets belongs to a group of tubulopathies characterized by hyperphosphaturia. PHEX gene mutation with function loss leads to increased FGF-23 levels. PHEX degrades FGF-23 into inactive fragments, preventing excessive phosphate excretion and the development of hypophosphatemia. In patients with PTH or vitamin D non- dependent hypophosphatemia, a diagnosis of X-chromosome linked hypophosphatemic rickets should be considered.

Dental and Endodontic Management in a Patient with Familial X-Linked Hypophosphatemic Rickets / Manejo Dental y Endodóntico en un Paciente con Raquitismo Hipofosfatémico Familiar Ligado al Cromosoma X

The term rickets refers to insufficient or retarded mineralization of the osteoide matrix. X-linked hypophosphatemic (XLH) rickets is a rare genetic disorder characterized by biochemical changes in bone mineralization due to inactivation of the phosphate regulating gene and primary defect of the osteoblasts. The aim of this article was to report a clinical case of XLH, its oral manifestations, periapical changes and dental management. A 31-year old woman female patient was referred to the school of dentistry with pain and sensitivity in the teeth. She had a childhood history of rickets, hypophosphatemia and alteration in Vitamin D. In the oral exam, enamel hypoplasia, microdontia, fistula, caries and periapical lesions and periodontal disease were diagnosed. The radiographic and tomographic exams exhibited the presence of periapical lesions involving various teeth with radiolucent images, suggestive of granuloma or periapical cysts. The treatme nt prioritized the urgency of eliminating pain and removing the foci of infection. Endodontic treatment began in the teeth that had fistula or periapical lesions and in parallel, oral hygiene guidance was provided and periodontal treatment was performed. There was an improvement in the clinical condition with reduction in inflammation and mobility of the teeth. Dentists and health professionals must evaluate the patient as a whole, considering the relations between systemic and oral health. Knowledge of systemic diseases associated with rickets and their characteristics is essential for making a correct oral diagnosis and planning the dental treatment.

El término raquitismo se refiere a la mineralización insuficiente o retardada de la matriz osteoide. El raquitismo hipofosfatémico ligado al cromosoma X (XLH) es un trastorno genético caracterizado por cambios bioquímicos en la mineralización ósea debido a la inactivación del gen regulador del fosfato y al defecto primario de los osteoblastos. El objetivo de este artículo fue reportar un caso clínico de XLH, sus manifestaciones orales, cambios periapicales y manejo dental. La paciente, una mujer de 31 años, acudió a la Clínica de Semiología de la UFPR con dolor y sensibilidad en varios dientes. Tenía antecedentes infantiles de raquitismo, hipofosfatemia y alteración de la vitamina D. En el examen oral se diagnosticó hipoplasia del esmalte, microdoontia, fístula, caries y lesiones periapicales y enfermedad periodontal. Los exámenes radiográficos y tomográficos mostraron la presencia de lesiones periapicales en varios dientes con imágenes radiolúcidas, sugestivas de granuloma o quistes periapicales. El tratamiento priorizó la urgencia de eliminar el dolor y remover los focos de infección. Se inició tratamiento de endodoncia en los dientes que presentaban fístula o lesiones periapicales y paralelamente se brindó orientación de higiene oral y se realizó tratamiento periodontal. Hubo una mejoría en la condición clínica con reducción de la inflamación y movilidad de los dientes. Los odontólogos y profesionales de la salud deben evaluar al paciente como un todo, teniendo en cuenta las relaciones entre salud sistémica y oral. El conocimiento de las enfermedades sistémicas asociadas al raquitismo y sus características es fundamental para realizar un correcto diagnóstico oral y planificar el tratamiento odontológico.

La accidentada historia del descubrimiento de la vitamina D, en su primer centenario / The checkered history of the discovery of vitamin D, in its first centenary

El año 2022 marca el primer centenario del descubrimiento de la vitamina D, hallazgo que recompensó la prolongada búsqueda de la causa del raquitismo, su prevención y tratamiento. Al mismo tiempo puso en marcha importantes investigaciones relaciona-das con su biotransformación y el mecanismo de su acción antirraquítica, además de estudios sobre diversos efectos biológicos sin relación directa con su papel en la salud ósea. Esta breve revisión se limitará a delinear la prehistoria de la vitamina D y los diversos estudios, básicos y clínicos, que condujeron a su descubrimiento y caracterización química. (AU)

The year 2022 marks the centenary of the discovery of vitamin D, a breakthrough that rewarded the long search for the cause of rickets, its prevention and treatment. At the same time, it launched important investigations related to its biotransformation and the mechanism of its antirachitic action, as well as studies on various biological effects without direct relation to its role in bone health. This brief review will be limited to an outline of the prehistory of vitamin D and the various basic and clinical studies that led to its discovery and chemical characterization. (AU)

Raquitismo hipofosfatémico ligado al cromosoma X: un reto diagnóstico y terapéutico / X - Linked Hypophosphatemic Rickets: A diagnostic and therapeutic challenge X-linked

La hipofosfatemia ligada al X es un desorden genético ocasionado por mutaciones del gen PHEX (phosphate regulating endopeptidase analog, X-linked). Esta afecta la codificación de una metaloproteasa que tiene como función inhibir el factor de crecimiento fibroblástico - 23 (FGF-23), promoviendo la pérdida renal de fosfato. A continuación, describimos el caso de un paciente de edad pediátrica a quien se le hace diagnóstico en la adolescencia con una mutación del gen PHEX. Posteriormente, la misma alteración genética fue encontrada en la madre, considerada como una mutación espontánea que fue trasmitida a su hijo. Esto aumenta la rareza del caso, donde el reto para diagnosticar esta patología necesita vencer dificultades administrativas, económicas y sociales. El diagnóstico y tratamiento oportuno ayudan a optimizar la talla final y minimizar todas las deformidades esqueléticas presentadas, tanto en la madre como en el hijo. En la actualidad se cuenta con el tratamiento tradicional y uno novedoso que fue ordenado para el paciente pediátrico de este reporte.

SUMMARY X-linked hypophosphatemia is a genetic disorder caused by PHEX gene mutations, which affects the encoding of a metalloprotease whose function is to inhibit fibroblastic growth factor-23 (FGF-23), promoting phosphate renal loss. Following we describe the case of a teenager diagnosed with a PHEX gene mutation. The same genetic alteration was found in the mother of the patient, considering a spontaneous mutation that was transmitted to her son, which makes the case, even rarer, where the diagnostic challenge needs to overcome administrative, economic and social difficulties. A timely diagnosis and treatment could help optimize the final height and minimize the skeletal deformities presented in both the mother and the child. Currently, there is a traditional treatment and a novel one that was ordered for the pediatric patient in this report.

X-linked hypophosphatemic rickets: a new mutation / Raquitismo hipofosfatêmico ligado ao X: uma nova mutação

Abstract Phosphopenic rickets may be caused by mutations in the PHEX gene (phosphate regulating endopeptidase homolog X-linked). Presently, more than 500 mutations in the PHEX gene have been found to cause hypophosphatemic rickets. The authors report a clinical case of a 4-year-old girl with unremarkable family history, who presented with failure to thrive and bowing of the legs. Laboratory tests showed hypophosphatemia, elevated alkaline phosphatase, normal calcium, mildly elevated PTH and normal levels of 25(OH)D and 1.25(OH)D. The radiological study showed bone deformities of the radius and femur. Clinical diagnosis of phosphopenic rickets was made and the genetic study detected a heterozygous likely pathogenic variant of the PHEX gene: c.767_768del (p.Thr256Serfs*7). This variant was not previously described in the literature or databases. Knowledge about new mutations can improve patient's outcome. Genetic analysis can help to establish a genotype-phenotype correlation.

Resumo O raquitismo fosfopênico pode ser causado por mutações no gene PHEX (ligado ao X do homólogo da endopeptidase que regula o fosfato). Atualmente, mais de 500 mutações no gene PHEX causam raquitismo hipofosfatêmico. Os autores relatam um caso clínico de uma menina de 4 anos com histórico familiar sem relevância, que apresentou falha no crescimento e arqueamento das pernas. Os exames laboratoriais mostraram hipofosfatemia, fosfatase alcalina elevada, cálcio normal, PTH levemente elevado e níveis normais de 25(OH)D e 1,25(OH)D. O estudo radiológico mostrou deformidades ósseas no rádio e no fêmur. O diagnóstico clínico do raquitismo fosfopênico foi realizado e o estudo genético detectou uma provável variante patogênica heterozigótica do gene PHEX: c.767_768del (p.Thr256Serfs*7). Esta variante não foi descrita anteriormente na literatura ou nas bases de dados. O conhecimento sobre novas mutações pode melhorar o desfecho de pacientes. A análise genética pode ajudar a estabelecer uma correlação genótipo-fenótipo.

Deficiencia de vitamina D asociada a hiperfosfatemia en niños / Vitamin D deficiency associated with hyperphosphatemia in children

RESUMEN Los niños con deficiencia de vitamina D pueden tener fósforo normal o alto a pesar de tener una prueba de hormona paratiroidea (PTH) elevada. El pseudohipoparatiroidismo (PHP) se caracteriza por cursar con hiperfosfatemia. La similitud que puede ocurrir entre la deficiencia de vitamina D asociada a hiperfosfatemia y el PHP hace importante revisar reportes de casos de deficiencia de vitamina D asociada a hiperfosfatemia para entender por qué puede ocurrir esta asociación y cuál es la relevancia de estudiar el nivel de vitamina D en niños con sospecha de PHP. El objetivo de esta revisión fue identificar reportes de niños con deficiencia de vitamina D asociada a hiperfosfatemia y discutir los mecanismos de esta asociación. Se identificaron reportes de 7 casos en niños. La deficiencia de vitamina D reduciría la respuesta fosfatúrica ante una PTH elevada. Se concluye que es importante descartar deficiencia de vitamina D en todo niño con sospecha de PHP.

ABSTRACT Children with vitamin D deficiency can have normal or high phosphorus despite having a high parathyroid hormone test (PTH). Pseudohypoparathyroidism (PHP) is characterized by hyperphosphatemia. The similarity that can occur between vitamin D deficiency associated with hyperphosphatemia and PHP makes it important to review case reports of vitamin D deficiency associated with hyperphosphatemia to understand why this association may occur and what is the relevance of studying the vitamin D level in children with suspected PHP. The aim of this review was to identify reports of children with vitamin D deficiency associated with hyperphosphatemia and to discuss the mechanisms of this association. Reports of 7 children cases were identified. Vitamin D deficiency could reduce the phosphaturic response to elevated PTH. It is concluded that it is important to rule out vitamin D deficiency in all children with suspected PHP.

Raquitismo vinculado al uso de fórmulas elementales: Reporte de caso / Rickets associated to the use of elemental formula: A case report

El raquitismo afecta la diferenciación y mineralización del cartílago de crecimiento como consecuencia, en última instancia, de una alteración en los niveles de fósforo y/o calcio. El secundario a la deficiencia de vitamina D es la forma más frecuente (raquitismo carencial). Las manifestaciones clínicas durante los primeros años de vida suelen comprometer en forma más marcada las epífisis de los huesos.Se describe el caso de un lactante de 8 meses con diagnóstico de alergia a la proteína de la leche de vaca que presentó múltiples fracturas patológicas mientras se encontraba bajo tratamiento con fórmulas lácteas a base de aminoácidos. Se efectuó el diagnóstico de raquitismo hipofosfatémico por deficiencia de fósforo y, tras 3 meses de tratamiento con sales de fosfato, calcio, calcitriol, el abandono paulatino de la leche elemental y el descenso gradual de la medicación antiácida, el paciente evolucionó con curación clínico-radiológica del cuadro

The rickets is a disease that affects the differentiation and mineralization of the growth cartilage, as an ultimate consequence of a balance loss in calcium and phosphate levels. Vitamin D deficiency is the most common cause of the rickets (nutritional rickets). Its clinical manifestation during the first years of life involves long bones epiphysis in a more severe way.We report an 8-month-old infant who was diagnosed with cow ́s milk protein allergy and suffered from multiple fractures while receiving elemental formula as part of his treatment. The final etiology was hypophosphatemic rickets secondary to phosphate deficiency, and after 3 months of phosphate, calcium and calcitriol supplementation, in addition to the gradually reduction of the proportion of elemental formula intake and the decline of the antacid doses, clinical and radiological heal was achieved.

Arte, historia y endocrinología / Art, history and endocrinology

Las enfermedades han sido representadas en el arte desde tiempos remotos. Las obras pictóricas muchas veces nos muestran trastornos que aún no se constituían como una entidad. Observar estos cuadros a la luz de la historia de las enfermedades nos da una perspectiva enriquecedora que nos ayuda a entender mejor dichas patologías. Se comenta un caso clínico endocrinológico pediátrico, la historia probable y su descripción física. Se revisa la historia de cómo se llegó a dilucidar la enfermedad y las claves de su tratamiento.

Diseases have been represented in art since ancient times. Paintings often show us disorders that had not yet been described as a pathological entity. Looking at these pictures in the light of the history of the diseases gives us an enriching perspective that helps us to better understand those pathologies. On this background a pediatric endocrinological clinical case, the most probable history and the features of the physical examination are discussed. The history of how the disease was uncovered and the keys of its treatment are reviewed.

Vitamin D-dependent rickets (VDDR) type 1: case series of two siblings with a CYP27B1 mutation and review of the literature / Raquitismo dependente de vitamina D: tipo 1: série de casos de dois irmãos com mutação CYP27B1 e revisão da literatura

Abstract Two siblings presented with clinical and biochemical features of rickets, initially suspected as hypophosphatemic rickets. There was no improvement initially, hence the siblings were reinvestigated and later diagnosed as having vitamin D-dependent rickets (VDDR) type 1 due to a rare mutation in the CYP27B1 gene encoding the 1α-hydroxylase enzyme. Both siblings improved with calcitriol supplementation. The initial presentation of VDDR is often confusing and algorithmic evaluation helps in diagnosis. We also present a brief review of the literature, including genetics.

Resumo Dois irmãos apresentaram características clínicas e bioquímicas do raquitismo, com suspeita clínica inicial de raquitismo hipofosfatêmico. Não houve melhora no início, portanto os irmãos foram reavaliados e, posteriormente, diagnosticados com raquitismo dependente de vitamina D (VDDR) tipo 1 devido a uma rara mutação no gene CYP27B1, que codifica a enzima 1a-hidroxilase. Ambos os irmãos melhoraram com a suplementação de calcitriol. A apresentação inicial do VDDR geralmente é confusa e a avaliação algorítmica ajuda no diagnóstico. Também apresentamos uma breve revisão da literatura, incluindo genética.

Prevalence of oral manifestations of hypophosphatemic rickets in patients treated in a peruvian pediatric hospital / Prevalencia de manifestaciones bucales del raquitismo hipofosfatémico de pacientes atendidos en un hospital pediátrico peruano

Objective: To describe the prevalence of oral manifestations of hypophosphatemic rickets in patients treated in a Peruvian referral pediatric hospital during the years 2012-2016. Material and methods: An observational, descriptive, retrospective, cross-sectional study was carried out. The sample consisted of patients diagnosed with hypophosphatemic rickets who attended the outpatient clinic of the Stomatology Service and the Genetics Service of the National Institute of Child Health (INSN), Lima, Peru, between the years 2012-2016. The research project was assessed and approved by the Research Ethics Committee of the Health Service. Medical records stored in a database of the health institution with the Code CIE E83.3, which corresponds to the diagnosis of Hypophosphatemic Rickets, were requested for the study. Results: Fifteen children received health care, of which only 10 were treated at the Stomatology Service. The distribution of the data was obtained from these 10 patients according to the proposed objective. A higher frequency of gingival lesions was found at the soft tissue level (41.18%); at the bone tissue level, only one case of dentigerous cyst was observed; and at the dental level, 90% of the patients had dental caries. Conclusion: The most frequent oral manifestations of hypophosphatemic rickets in pediatric patients treated at the National Institute of Child Health (2012-2016) were gingivitis and dental caries.

Objetivo:Describir la prevalencia de las manifestaciones bucales del raquitismo hipofosfatémico de pacientes atendidos en un hospital pediátrico de referencia peruano durante los años 2012-2016. Material y Métodos:Se realizó un estudio tipo observacional, descriptivo, retrospectivo, transversal. Para la selección de la muestra se consideró a los pacientes que acudieron a la consulta externa del Servicio de Odontoestomatología y el Servicio de Genética del Instituto Nacional de Salud del Niño, Lima, Perú; en el periodo comprendido entre los años 2012-2016 y que presentaron como diagnóstico Raquitismo Hipofosfatémico. El proyecto de investigación fue evaluado por un Comité de Ética en Investigación del servicio de salud. Se solicitaron las historias clínicas consignadas en una base de datos de la institución de salud con el Código CIE E83.3, que corresponde a este diagnóstico. Resultados: Fueron atendidos 15 niños, de los cuales solo 10 fueron tratados en el Servicio Odontoestomatología; siendo de estos 10 pacientes la distribución de los datos obtenidos según el objetivo propuesto. Se encontró mayor frecuencia de lesiones a nivel de tejido blando de gingivitis con 41.18%, a nivel de tejido óseo solo se presentó un caso de quiste dentígero; y a nivel de tejido dental el 90% de los pacientes presentó caries dental. Conclusión: Las manifestaciones bucales más frecuentes del raquitismo hipofosfatémico de pacientes pediátricos atendidos en el Instituto Nacional de Salud del Niño (2012-2016), fueron la gingivitis y caries dental.

Efecto de la suplementación con vitamina D en dosis única sobre el estado nutricional de vitamina D / Effect of vitamin D supplementation as a single dose on the nutritional status of vitamin D

INTRODUCCIÓN: El primer año de vida es un periodo de riesgo de deficiencia de vitamina D (VD). La administración de 400 UI diarias de VD no tiene una adherencia del 100%, en cambio dosis únicas de 100.000 UI de VD oral son seguras en recién nacidos. OBJETIVO: Comparar el efecto de la suplementación oral de VD en dosis única de 100.000 UI al mes de edad vs dosis diarias de 400 UI sobre las concentraciones séricas de VD, a los 6 meses de vida. SUJETOS Y MÉTODOS: Ensayo clínico aleatorizado, sin enmascaramiento. Se incluyeron 84 lactantes sanos de 1 mes de vida, asignados al azar al grupo de estudio (GE) que recibió una dosis única de VD de 100.000 UI oral o al grupo control (GC), que recibió dosis diarias de VD de 400 UI oral del 1er al 6to mes de vida. A los 6 meses de edad se determinó la concentración sérica de VD. RESULTADOS: 65 lactantes terminaron el estudio, 36 en GE y 29 en GC. No se encontró deficiencia de VD. La insuficiencia de VD fue de 5,5% y 6,8% en el GE y GC, respectivamente. La concentración sérica de VD a los 6 meses de vida, fue de 38,8 ± 5,2 ng/ml y 39,7 ± 6,3 ng/ml para GE y GC, respectivamente (NS). CONCLUSIONES: La suplementación con 100.000 UI de VD única al mes de edad logra concentraciones séricas de VD a los 6 meses de vida, similares a dosis diarias de 400 UI de VD, del 1er al 6to mes.

INTRODUCTION: Infants are a group at risk of vitamin D (VD) deficiency. The administration of 400 IU of VD per day during the first year of life does not achieve 100% adherence. A single dose of 100,000 IU of oral VD is safe in newborns. OBJECTIVE: To compare the effect of oral administration of VD between a single dose of 100,000 IU at one month of age vs daily doses of 400 IU on serum concentrations of VD, at 6 months of age. SUBJECTS AND METHOD: Randomized clinical trial, without masking. 84 healthy infants were included at 1 month of age, randomized to the study group (SG) receiving a single oral dose of 100,000 IU or to the control group (CG), who received daily oral doses of VD of 400 IU from the 1st to the 6th month of life. At 6 months of life, the serum concentration of VD was determined. RESULTS: 65 infants completed the study, 36 in SG and 29 in CG. No VD deficiency was found. VD insufficient was 5.5% and 6.8% in the SG and CG, respectively. The serum concentration of VD at six months of age was 38.8 ± 5.2 ng/ml and 39.7 ± 6.3 ng/ml for the SG and CG, respectively (NS). CONCLUSIONS: Supplementation of 100,000 IU of VD at one month age achieves serum concentrations of VD at 6 months of life similar to the administration of daily doses of 400 IU of VD from the 1st to the 6th month.

Rickets in white-eared opossums (Didelphis albiventris) / Raquitismo em gambás-de-orelha-branca (Didelphis albiventris)

Two young opossums were necropsied and diagnosed with rickets. This study aims to describe the clinical-pathological aspects of rickets in Didelphis albiventris. Macroscopically, the opossums presented kyphosis and scoliosis, lateral deviation of the limbs in varus, locomotion difficulty, and enlargement with softening of costochondral junctions (rickety rosary). Samples of bones and joints were processed for hematoxylin and eosin staining and Masson's trichrome. Microscopically, we observed thickening of the epiphyseal plate, characterized by irregular and multifocal proliferation of serialized and hypertrophic cartilage zones, which formed circular groups of large, dysplastic chondrocytes towards the spongy zone, often surrounded by non-mineralized osteoid tissue. In the cortical bone, there were pale eosinophilic zones around the Havers channels consistent with non-mineralized osteoid. The staining of Masson's trichrome evidenced the accumulation of osteoid tissue in cortical and trabecular bones. It is possible that a mixed cause of absorption deficiency of vitamin D3 associated with an unbalanced Ca:P diet based on lactose-free milk and fruits may have triggered the disease.(AU)

Dois gambás jovens foram necropsiados e diagnosticados com raquitismo. O objetivo do trabalho é descrever os aspectos clínico-patológicos de raquitismo em Didelphis albiventris. Macroscopicamente os gambás apresentaram cifose e escoliose, desvio lateral dos membros em varus, dificuldade de locomoção e alargamento com amolecimento das junções costocondrais (rosário raquítico). Amostras dos ossos e articulações foram processadas para coloração de hematoxilina e eosina e Tricrômico de Masson. Microscopicamente havia espessamento da placa epifisária, caracterizada pela proliferação irregular e multifocal das zonas de cartilagem seriada e hipertrófica, que formavam grupos circulares de condrócitos grandes, displásicos em direção a zona esponjosa frequentemente cercados por tecido osteoide não mineralizado. No osso cortical haviam zonas eosinofílicas pálidas ao redor dos canais de Havers consistentes com osteoide não mineralizado. A coloração de Tricrômico de Masson evidenciou o acúmulo de tecido osteoide no nosso cortical e trabecular. Acredita-se que uma causa mista de déficit de absorção de vitamina D3 associada a uma dieta desbalanceada em Ca:P a base de leite sem lactose e frutas tenha desencadeado a doença.(AU)

Neumonía a repetición en un paciente con deformidades óseas: a propósito de un caso de raquitismo / Recurrent pneumonia in a patient with bone deformity: a case report of ricketts

El raquitismo es una enfermedad ósea infrecuente asociada a la disminución de niveles séricos de calcio o fosfato, la mayoría de los casos como consecuencia de déficit nutricional, aunque puede presentarse por mutaciones genéticas o defectos adquiridos del metabolismo. El cuadro clínico es heterogéneo y depende de la edad de presentación; manifestándose con ensanchamiento y retraso de la mineralización de la placa de crecimiento ósea. Se presenta el caso de un niño indígena de 11 meses de edad con historia de neumonía recurrente, al examen físico, presentaba hipotonía muscular generalizada, tórax con rosario costal y deformidad en extremidades, con paraclínicos: hipocalcemia e hipofosfatemia, fosfatasa alcalina y hormona paratiroidea elevadas, niveles de 25-hidroxi-vitamina normales-altos y con valor de 1,25-dihidroxi-vitamina D muy bajo, se sugirió el diagnóstico de raquitismo dependiente de vitamina D tipo 1A severo, una forma infrecuente de esta patología.

Ricketts is a rare bone disease associated with low serum levels of calcium and phosphate. Most of the cases occur as a consequence of nutritional deficits, but genetic mutations or acquired metabolic defects may account for it. Clinical presentation is heterogenous depending on age at presentation, manifesting as widening and retardation of mineralization of the growing bone plate. We present the case of a 11 month of age child with a history of recurrent pneumonia presenting with generalized muscle hypotonia, deformed chest and bowed extremities with hypocalcemia and hypophosphatemia, elevated levels of alkaline phosphatase and parathyroid hormone, high levels of 25-hidroxy-vitamine D3 and very low levels of 1,25-dihidroxy-vitamine D3 suggesting the diagnosis of severe vitamin D type 1A rickets, a rare form of this disease.

Kasugamycin on Leifsonia xyli subsp. xyli in the in vitro culture of sugarcane / Efeitos da Kasugamicina em Leifsonia xyli subsp. xyli na cultura in vitro de cana-de-açúcar

ABSTRACT: One of the significant obstacles to the growth of sugarcane production is the infection by phytopathogens, mainly by the bacterium Leifsonia xyli subsp. xyli (Lxx) causal agent of Ratoon stunting disease. Thus, this research aimed to evaluate the effects of kasugamycin on the in vitro growth of sugarcane, as well as its effect on the bacterium Lxx. Explants of strain SP791011 from sugarcane were inoculated in MS culture medium supplemented with the antimicrobial kasugamycin at concentrations of 0.00; 0.87; 1.08; 1.74 and 3.48 mL.L-1, where they remained for 30 days. After this period, the survival rate, shoot number per explant, height of the explants, phytomass, dry phytomass and phytosanitary were evaluated based on the presence of genomic DNA of Lxx. It was verified that the culture in kasugamycin influenced the morphological variables negatively; nevertheless, the antimicrobial did not demonstrate phytotoxicity to the plants. All treatments tested in this experiment were diagnosed as positive, with DNA amplification for Lxx, despite it was observed a reduction in bacterial load, suggesting that kasugamycin at higher doses can be evaluated as an attempt to eliminate the bacterium in the in vitro cultivation of sugarcane.

RESUMO: Um dos maiores entraves para o crescimento da produção de cana-de-açúcar é a infecção por fitopatógenos, principalmente pela bactéria Leifsonia xyli subsp. xyli (Lxx), agente causal do raquitismo-da-soqueira, doença que mais causa perdas a cultura. Assim, este trabalho teve como objetivo, avaliar os efeitos do antimicrobiano casugamicina sobre o crescimento in vitro, bem como seu efeito sobre a infecção endógena por Lxx em cana-de-açúcar. Explantes da variedade SP791011 de cana-de-açúcar foram inoculados em meio de cultura MS suplementados com o antimicrobiano nas concentrações de 0,00; 0,87; 1,08; 1,74 e 3,48 mL.L-1, em que permaneceram por 30 dias. Após este período, foi avaliada a taxa de sobrevivência, número de brotações por explante, altura dos explantes, fitomassa, fitomassa seca e fitossanidade em relação à presença de DNA genômico de Lxx. Foi verificado que o cultivo em casugamicina influenciou de forma negativa nas variáveis morfológicas, apesar disso, o antimicrobiano não mostrou fitotoxidade às plantas. Todos os tratamentos testados neste experimento foram diagnosticados como positivos, com amplificação de DNA para Lxx, apesar de ter sido observada uma redução na carga bacteriana, sugerindo que a casugamicina em doses superiores pode ser avaliada como alternativa na tentativa de eliminar completamente a bactéria no cultivo in vitro de cana-de-açúcar.

Uveítis anterior aguda asociada a raquitismo renal hipofosfatémico / Acute anterior uveítis associated to hypophosphatemic renal ricketts

Los raquitismos hipofosfatémicos hereditarios son un grupo de enfermedades caracterizadas por la pérdida renal de fosfatos. Cursan con hipocrecimiento disarmónico y deformidades óseas. La forma más común es el raquitismo hipofosfatémico ligado al cromosoma X, el cual es causado por mutaciones inactivantes en el gen PHEX. El objetivo de nuestro trabajo fue describir las alteraciones oculares encontradas y la evolución clínica en un paciente con raquitismo hipofosfatémico hereditario y uveítis anterior. Se presenta un niño de 9 años de edad con diagnóstico de raquitismo hipofosfatémico hereditario, valorado en el Servicio de Uveítis del Instituto Cubano de Oftalmología Ramón Pando Ferrer por presentar dolor ocular y molestias a la luz en el ojo derecho. En la exploración oftalmológica se constata una uveítis anterior con hipopión en el ojo derecho y depósitos de cristales en todo el espesor corneal y el iris en ambos ojos. Se indicaron esteroides tópicos con resolución del proceso inflamatorio. Los hallazgos en el segmento anterior del paciente son sugestivos de cistinosis, donde el acúmulo de cristales es la alteración corneal más típica de las manifestaciones oculares, con una incidencia del 90 por ciento en niños menores de un año, y los primeros órganos afectados son los riñones. Los raquitismos hipofosfatémicos hereditarios pueden cursar con depósitos de cristales corneales y procesos inflamatorios de la úvea anterior(AU)

Hereditary hypophosphatemic rickets are a group of diseases characterized by renal loss of phosphates. They appear with disharmonic hypogrowth and bone deformities. The most common form is the X-chromosome-linked hypophosphatemic rickets which is caused by inactivating mutations in PHEX gene. The objective of our work was to describe the ocular alterations and the clinical evolution in a patient with hereditary hypophosphatemic rickets and previous uveitis. Here is the case of a 9 years-old boy diagnosed with hereditary hypophosphatemic rickets, who was seen at the Uveitis Service of Ramon Pando Ferrer Cuban Institute of Ophthalmology. He presented with ocular pain and feeling of discomfort to light in his right eye. The ophthalmological exam yielded anterior uveitis with hypopyon in his right eye and crystal depots in the whole corneal thickness and the iris of both eyes. Topical steroids were prescribed to treat the inflammatory process. The findings in the anterior segment of the patients indicated the presence of cystinosis in which the accumulation of crystals is the most typical corneal alteration among the ocular manifestations. Its incidence reaches 90 percent in under one year-old children and the first affected organs are the kidneys. The hereditary hypophosphatemic rickets may appear with corneal crystal depots and inflammatory processes in the anterior uvea(AU)

Raquitismo carencial: a propósito de un caso

El raquitismo es una enfermedad que se caracteriza por una deficiencia en la osificación de los huesos, afectando a las metáfisis y por tanto a los niños en su etapa de crecimiento, con una expresión clínica común aun teniendo varias etiologías, entre ellas la carencia de vitamina D3, siendo ésta causa poco frecuente en nuestro país debido a la acción de los rayos solares UVB por ser un país subtropical. El motivo de la presentación es el caso de un niño de 2 años 3 meses portador de una hipoplasia renal congénita bilateral, que era sometido a diálisis peritoneal ambulatoria por ERC desde los 3 meses de edad. Ingresó al hospital para ser tratado por disfunción de la diálisis peritoneal causada por obstrucción distal del catéter, en el examen al ingreso se constataron hipocrecimiento y retraso del desarrollo motor importante, así como signos clínicos, radiográficos y de laboratorio de raquitismo activo, presentando en la sangre niveles de vitamina D2 muy bajos lo que reveló ser raquitismo carencial, iniciándose tratamiento con Calcitriol a 3.000 UI/día, teniendo una buena respuesta a la medicación, mejorando las lesiones óseas y del desarrollo motor comenzando a ponerse de pie y dando pasos con apoyo.

Rickets is a disease characterized by a deficiency in bone ossification, affecting the metaphyses, and therefore children during their growth stages, with a common clinical expression even though there are several etiologies, among them the lack of vitamin D3, a rare cause in our subtropical country due to the action of UVB rays. We present the case of a 2-year-old 3-month-old child with bilateral congenital renal hypoplasia who underwent outpatient peritoneal dialysis for CKD starting at 3 months of age. She was admitted to the hospital to be treated for dysfunction of peritoneal dialysis caused by a distal catheter obstruction. On her admission examination, there was evidence of growth retardation and delayed motor development, as well as clinical, radiographic and laboratory signs of active rickets. Blood levels of vitamin D2 very low, which showed this to be a deficiency rickets, She was treated with Calcitriol at 3,000 IU / day, and had a good response to the medication, showing improvement in her bone lesions and motor development, beginning to stand up and taking steps with support.

Raquitismo hipofosfatêmico: relato de caso / Hypophosphatemic rickets: case report

RESUMO Objetivo: O raquitismo hipofosfatêmico precisa ser precocemente diagnosticado porque seu tratamento previne sequelas incapacitantes. Este relato alerta para a doença. Relato de caso: Relato de perfil metabólico, depuração de creatinina, estado nutricional e desenvolvimento pôndero-estatural de paciente com características clínico-laboratoriais de raquitismo hipofosfatêmico, atendido em ambulatório de tubulopatias por período de 12 meses. Chegou ao serviço após tempo prolongado acamado, dependente de ventilação mecânica e com perfil metabólico ósseo alterado. Terapêutica consistiu na administração de fósforo (inicial: 65 mg/kg/dia, final: 24,2 mg/kg/dia), cálcio (inicial: 127 mg/kg/dia, final: 48,4 mg/kg/dia) e calcitriol (inicial: 0,06 mcg/kg/dia, final: 0,03 mcg/kg/dia), e a análise constou da descrição das consultas, utilizando-se mediana de exames laboratoriais e dados antropométricos. Observou-se nítida melhora inicial do padrão respiratório do paciente, que evoluiu com ventilação espontânea e deambulação autônoma; com exames laboratoriais: cálcio (mg/dL) inicial 7,1, final 10,1; fósforo (mg/dL) inicial 1,7, final 3,2; magnésio (mg/dL) inicial 1,5, final 2,1; paratormônio (pg/L) inicial 85,8, final 52,7; fosfatase alcalina (UI/L) inicial 12660, final 938; e melhora do desenvolvimento pôndero-estatural (escore Z: E/I inicial: -6,05, final -3,64; P/I: inicial -2,92, final -1,57) com presença de litíase transitória. A depuração de creatinina (mL/min/1,73 m2sc) foi constante durante o seguimento. O tratamento propiciou benefícios clínicos, bioquímicos e nutricionais, mas, apesar da boa resposta inicial, a família abandonou o seguimento por dois anos, apresentando o paciente piora da deambulação e das deformidades esqueléticas. Comentários: Não apenas diagnóstico precoce é necessário, como também a adesão ao tratamento é fundamental para o sucesso na condução dessa patologia.

ABSTRACT Objective: Early diagnosis and immediate treatment of hypophosphatemic rickets is of utmost importance as it may prevent subsequent sequelae. This report aims at warning pediatricians to consider the presence of the disease. Case description: Description of the metabolic profile, creatinine clearance, nutritional status, weight and body structure of a patient who presented the clinical-laboratorial characteristics of hypophosphatemic rickets and was followed in an outpatient clinic for tubulopathies over the period of 12 months. The patient had been bedridden for some time, was dependent on mechanical ventilation and presented an altered metabolic bone condition. Treatment was phosphate (initial: 65 mg/kg/day and final: 24,2 mg/kg/day), calcium (initial: 127 mg/kg/day, final: 48,4 mg/kg/day) and calcitriol (initial: 0.06 mcg/kg/day, final: 0.03 mcg/kg/day). The patient improved, evolving into spontaneous breathing and walking unaided. Laboratory results: calcium (mg/dL) initial 7.1, final 10.1; phosphate (mg/dL) initial 1.7 final 3.2; magnesium (mg/dL) initial 1.5 final 2.1, parathyroid hormone (pg/l) initial 85.8, final 52.7, alkaline phosphatase (UI/l) initial 12660, final 938; there was also improvement in weight/structural development (Z score: H/A initial: -6.05, final -3.64; W/A: initial -2.92, final -1.57) with presence of transitory gallstones. Creatinine clearance (mL/min/1.73m2bsa) was constant. The medication improved his laboratory results and nutritional status, but the patient did not return for two years for follow-up and, during this period, his condition has noticeably deteriorated. Comments: Early diagnosis and follow-up are essential in dealing with this pathology.

Raquitismo hipofosfatémico. Presentación de un caso / Hypophosphatemic rickects. Case Presentation

El raquitismo es un trastorno causado por una falta de vitamina D, calcio o fósforo, que lleva a que se presente reblandecimiento y debilitamiento de los huesos. Los raquitismos resistentes son un conjunto heterogéneo de enfermedades denominadas así porque, aunque presentan clínica y radiografía típicas del raquitismo carencial, no responden al tratamiento convencional con vitamina D. Dentro de estos últimos se encuentra el raquitismo hipofosfatémico, enfermedad genética que puede expresarse con varios desórdenes. Se presenta el caso de una niña de tres años de edad que se remitió a consulta de genética clínica por baja talla y deformidad en ambas piernas. Después del interrogatorio y el examen físico, se realizó estudio radiológico y química sanguínea, con lo que se llegó al diagnóstico de esta enfermedad. Se considera valioso realizar diagnóstico oportuno que beneficie el seguimiento y tratamiento en equipo multidisciplinario, que permita, además, brindar un adecuado asesoramiento genético a los familiares, razones por las cuales se decidió la presentación del caso.

Rickects is a disturbance caused by a lack of vitamine D, calcium or phosphorus which leads to bone softening and weakening. Resistant rickects are a heterogeneous group of diseases so called because they show clinical and radigraphic characteristics which are typical of a deficency rickects, there is no response to tretament with vitamine D. Among these it is found Hypophosphatemic rickects which is a genetic disease and may present with various disorders. A case of a 3 year old girl referred to the genetic consultation due to short size and deformity in both legs. After questioning and physical examination a radiologic and blood chemestry study was performed resulting in the diagnosis of this disease. It is considered valuable to make a timely diagnosis which favours the follow up and treatment in a multidispline team, allowing, in addition, to provide genetic advisory to relatives. These are the reasons for this case presentation.