Mielopatía por déficit de cobre: serie de casos y revisión de la literatura / Myelopathy due to copper deficiency: A case series and review of the literature

El déficit de cobre puede presentarse como una mielopatía y manifestarse como una ataxia sensorial secundaria a una desmielinización de los cordones posteriores de la médula espinal. Puede acompañarse de citopenias, principalmente anemia y leucopenia. Se presenta una serie de casos de tres pacientes con mielopatía por déficit de cobre, diagnosticados y manejados desde el año 2020 al 2022 en un hospital universitario de alta complejidad en Colombia. Dos de los casos eran mujeres. El rango de edad fue entre 57 y 68 años. En los tres casos, los niveles séricos de cobre estaban disminuidos y en dos de ellos, se descartaron diferentes causas de mielopatía que afectan los cordones posteriores de la médula espinal como el déficit de vitamina B12, vitamina E y ácido fólico, tabes dorsal, mielopatía por virus de la inmunodeficiencia humana, esclerosis múltiple e infección por el virus linfotrópico humano de tipo I y II, entre otras. Sin embargo, un paciente tenía deficiencia de vitamina B12 asociada con de cobre en el momento del diagnóstico de la mielopatía. En los tres casos hubo ataxia sensitiva y en dos, la paraparesia fue el déficit motor inicial. Se deben incluir siempre la determinación de los niveles de cobre dentro del abordaje diagnóstico de todo paciente con enfermedad gastrointestinal crónica, con diarrea crónica, síndrome de mala absorción o reducción significativa de la ingestión en la dieta, y que desarrolle síntomas neurológicos sugestivos de compromiso de los cordones, ya que se ha reportado que el retraso en el diagnóstico de las mielopatías se asocia con pobres desenlaces neurológicos.

Copper deficiency can present as myelopathy by the manifestation of sensory ataxia, secondary to demyelination of the posterior cords of the spinal cord, accompanied by cytopenia, mainly anemia, and leukopenia. Case series study of three patients with myelopathy due to copper deficiency, diagnosed and managed from 2020 to 2022 in a highly complex university hospital in Colombia. Regarding gender, two cases were female patients. The age range was between 57 and 68 years. In all three cases serum copper levels were decreased, and in two of these, different causes of myelopathy affecting the posterior cords of the spinal cord were ruled out, such as vitamin B12, vitamin E and folic acid deficiency, tabes dorsalis, myelopathy due to human immunodeficiency virus, multiple sclerosis and infection by the human lymphotropic virus type I and II, among others. However, at the moment of the myelopathy diagnosis, one patient had vitamin B12 deficiency associated with copper insufficiency. All three cases presented sensory ataxia, and in two, paraparesis was the initial motor deficit. The diagnostic approach must include copper levels assessment in every case of patients with chronic gastrointestinal pathology, chronic diarrhea, malabsorption syndrome, or significant reduction in dietary intake; and the development of neurological symptoms that may suggest cord involvement. It has been reported that a delay in diagnosis can lead to poor neurological outcomes.

Subcutaneous administration of levothyroxine: a novel approach to refractory hypothyroidism - A review and a case report

SUMMARY Treatment-refractory hypothyroidism is a common clinical finding. Substantial causes include poor compliance and intake failure as well as gastrointestinal diseases, such as inflammatory bowel disease and short bowel syndromes. Increasing oral dosage of levothyroxine (LT4) is not always effective. Therefore, alternative routes of administration are necessary. In this report, we evaluate alternative treatment modalities for refractory hypothyroidism and present a 28-year-old woman with intestinal drug malabsorption successfully treated by subcutaneous LT4 administration. In this patient, a parenteral form of LT4, 500 μg/5 ml, was administered subcutaneously in a split dosage regimen. Blood hormone levels returned to normal within a few days and remained stable over an 8-month follow-up period.

Coagulopatía asociada a síndrome de malabsorción por enfermedad celíaca / Coagulopathy associated with celiac disease malabsorption syndrome

This article describes a 19-y-old patient with abdominal pain and signs of malnutrition. She had been treated previously with an antibiotic for chronic diarrhea. Laboratory analyses showed the presence mild hypoalbuminemia, and considerably prolonged prothrombin time. Tests revealed that hemostasis improved after the patient received fresh frozen plasma and vitamin k. A coagulation profile showed a decrease in clotting factors V, VII, IX, and fibrinogen. Positive serology (immunoglobulin A antitissue transglutaminase and immunoglobulin A antiendomysial antibodies) and small bowel mucosal histopathology confirmed the presence of celiac disease (CD). The girl recovered completely after she was put on a gluten-free diet. Vitamin K­deficiency is a rare complication that occurs in celiac disease manifestations. In addition to antibiotic therapy, treatment with other drugs that influence vitamin K resorption and metabolism may increase the risk of bleeding in patients with CD with hypoprothrombinemia.

Mala absorción de glucosa y de galactosa y su asociación con el síndrome de Down / Malabsorption of glucose and galactose and its relation with Down sydrome

Introducción: La malabsorción de glucosa y de galactosa es una enfermedad genética autosómica recesiva debida a una mutación que afecta al cotransportador de sodio-glucosa. Objetivo: Describir una asociación infrecuente entre el síndrome de Down y la mala absorción de glucosa y de galactosa. Presentación del caso: Niño desnutrido de 3 ½ meses de edad con síndrome de Down, de padres consanguíneos. Presentó precozmente diarrea explosiva, vómitos con deshidratación. Se mejoró tras la eliminación de la alimentación oral y la perfusión hidroelectrolítica y empeoró con la utilización de las sales de rehidratación oral y las fórmulas lácteas, sin proteínas de leche de vaca. El estudio de las heces mostró un pH fecal /5, presencia de glucosa, ionograma de las 24 horas fue: sodio 0,5 mEq (1-10), potasio 2,6 mEq (8-22) y el cálculo realizado para distinguir entre diferentes causas de diarrea dio aumentado: 168 mOsm/kg (50-125). Ante este cuadro clínico se consideró el diagnóstico de malabsorción de glucosa y de galactosa sobre todo tras la mejora de la sintomatología bajo dieta exclusivamente azucarada con fructosa. Conclusiones: Es importante tener en cuenta la malabsorción de glucosa y de galactosa dentro de los diagnósticos diferenciales de las diarreas acuosas congénitas. El diagnóstico precoz y la dieta adecuada con fructosa evitan deshidratación y malnutrición. La particularidad de nuestro caso es la asociación de la malabsorción de glucosa y de galactosa con el síndrome de Down, que, según nuestro conocimiento, es la primera vez que se describe y podría aumentar la morbilidad(AU)

Introduction: Malabsorption of glucose and galactose is a genetic autosomic recesive disease caused by a mutation that affects the co-transportator of sodium-glucose. Objective: To describe an unfrequent relation between the Down syndrome and the malabsortion of glucose and galactose. Case presentation: Undernourished child, 3 and half months old with Down syndrome from parents by blood. He early presented explosive diarrhea and vomiting with dehydration. He improved his state after elimination of oral feeding and a hydroelectrolitic perfusion, and his state worsened with the use of oral rehydration salts and dairy formula, even without cow´s milk proteins. The study of feces showed a fecal pH /5, presence of glucose, and the ionogram after 24 hours showed: sodium 0,5mEg (1-10), potasium 2,6 mEg (8-22) and the calculation made to identify the different causes of diarrhea was increased: 168 mOsm/kg (50-125). Having this clinical records, it was considered a diagnostic of glucose and galactose malabsorption, mainly after the improvement of the symptoms under a diet exclusively sugared with fructose. Conclusions: It is important to take into account glucose and galactose malabsortion in the differential diagnosis of congenital watery diahrrea. The early diagnosis and an adequate diet with fructose avoid dehytration and malnutrition. The particularity of this case is the relation of glucose and galactose malabsorption with Down syndrome, that according to our knowledge is the first time it is described and it can increase the morbility(AU)

Sobrepeso y obesidad en la enfermedad celiaca activa: posibles mecanismos fisiopatológicos / Overweight and obesity in active celiac disease: possible pathophysiological mechanisms

RESUMEN La enfermedad celiaca (EC) es una enteropatía crónica del intestino delgado, mediado por una respuesta inmune, gatillada por la exposición al gluten en individuos genéticamente susceptibles. La presentación clínica de la EC es variada y conduce a mala absorción. El estado nutricional en el momento del diagnóstico de la EC depende del tiempo en que la enfermedad ha estado activa, la extensión de la inflamación intestinal, grado de mala absorción e ingesta alimentaria. Sin embargo, en los últimos años se ha observado un cambio epidemiológico del estado nutricional en los pacientes celiacos al momento del diagnóstico. La presente revisión tuvo por objetivo realizar un análisis descriptivo de la presencia de obesidad en pacientes celiacos y de los posibles mecanismos fisiopatológicos que la explicarían.

ABSTRACT Celiac disease (CD) is a chronic enteropathy of the small intestinal, mediated by an immune response triggered by exposure to dietary gluten in genetically predisposed individuals. The clinical presentation of CD is varied and leads to malabsorption. Nutritional status at the time of diagnosis of CD depends on the time in which the disease has been active, the extent of intestinal inflammation, degree of malabsorption, and dietary intake. However, in recent years an epidemiological change of nutritional status has been observed in celiac patients at the time of diagnosis. The objective of this review was to perform a descriptive analysis of the presence of obesity in celiac patients and the possible physiopathological mechanisms that would explain it.

Hipotiroidismo refractario idiopático: un caso clínico / Idiopathic refractory hypothyroidism: case report

Introducción: El hipotiroidismo constituye una patología frecuente, y su tratamiento habitual es el suplemento de levotiroxina (LT4) oral (VO). Sin embargo, existen casos inhabituales donde no es posible corregir esta condición a pesar de la utilización de LT4 en dosis alta. El hipotiroidismo refractario se define como la persistencia del hipotiroidismo a pesar del uso de LT4 > 1,9 ug/kg/día. La prevalencia del hipotiroidismo refractario no ha sido suficientemente documentada hasta ahora. Descripción del caso: Mujer de 53 años con antecedentes de hipotiroidismo, obesidad, dislipidemia, hipertensión arterial e insulinorresistencia. Fue derivada desde APS a nivel terciario por hipotiroidismo persistente a pesar del uso de LT4 800 ug/día y liotironina 80 ug/día. En forma ambulatoria se descartaron distintas causas, como mala adhesión al tratamiento, pseudo-malabsorción, síndromes de malabsorción; interacciones farmacológicas o interacciones alimentarias. Ante esto, y manteniéndose en su condición, se decide hospitalizar. Durante la hospitalización se prueban distintas fórmulas de administración. Finalmente, se logra respuesta adecuada con LT4 por vía rectal 100 ug/día asociado a 100 ug c/12 horas VO. Discusión: A pesar de no contar con herramientas óptimas para enfrentar este caso, se logró aplicar una estrategia sistemática especializada, que permitió un buen manejo de la paciente. Luego de probar distintas formulaciones de hormonas tiroideas, se logró respuesta mediante la administración por vía rectal, lo cual sugiere que esta paciente presentaba algún trastorno celular/bioquímico intestinal alto, que impedía la absorción óptima de LT4 VO. Conclusiones: La principal fortaleza de este trabajo consiste en la demostración de la utilidad práctica, en un contexto de recursos limitados, de una estrategia de estudio y tratamiento sistemático del hipotiroidismo refractario, lo cual ha sido escasamente publicado en la literatura internacional. Además, se recalca la importancia de una intervención especializada oportuna para evitar los riesgos sistémicos asociados a dosis altas de hormonas tiroideas.

Introduction: Hypothyroidism is a common condition, and its usual treatment is the supplement of oral levothyroxine (po). However, there are unusual cases where it is not possible to correct this condition despite the use of high-dose levothyroxine. Refractory hypothyroidism is defined as the persistence of hypothyroidism despite the use of levothyroxine > 1.9 ug/kg/ day. The prevalence of refractory hypothyroidism has not been sufficiently documented so far. Case description: 53 year old woman with a history of hypothyroidism, obesity, dyslipidemia, hypertension and insulin resistance. She was sent from primary care to tertiary level due to persistent hypothyroidism despite the use of 800 ug/day levothyroxine and liothyronine 80 ug/ day. On an outpatient basis, different causes were excluded as poor adherence to treatment, pseudo-malabsorption, malabsorption syndromes; drug interactions or food interactions. Given this, and staying on her condition, it was decided to hospitalize. Different forms of administration were tested during hospitalization. Finally, got adequate response with levothyroxine rectally 100 ug/day associated with 100 ug po bid. Discussion: Despite not having optimum tools to deal with this case, it was succeeded thanks to the implementation of a specialized systematic strategy. After testing different formulations of thyroid hormones, a positive response by rectal administration was achieved, which suggests that this patient presented any high intestinal cell/biochemist disorder that prevented the optimal absorption of levothyroxine po. Conclusions: The main strength of this work consists in demonstrating the practical utility, in a context of limited resources, of a study and systematic treatment strategy of refractory hypothyroidism, which has barely been published in the international literature. It is also highlighted the importance of an early specialized intervention to prevent the systemic risks associated with high doses of thyroid hormones.

Dolor y distensión abdominal: abordaje diagnóstico a distintas edades / Abdominal pain and distention: diagnostic approach at different ages

Fluctuating abdominal pain and bloating suggest gastrointestinal origin with multiple causes. In adults, patients fulfilling the Rome criteria for irritable bowel syndrome (IBS) have a low probability of neoplasms or intestinal inflammatory diseases. In these patients it is cost effective to request fecal calprotectin and celiac disease serology. Due to the high probability of nocebo effect, the diagnosis of sensitivity to non celiac and food allergies should require a blind rechallenge. It is recommended to evaluate other non ominous diagnostic options in a second stage if there is not good control of symptoms. In adults that do not fulfil the criteria of IBS or in adults older than 50 it is often necessary to request more studies, including endoscopic examinations. In children, abdominal pain and bloating occur frequently in the context of excessive consumption of sugar (including fructose, lactose and sorbitol). In infants it can occur in the context of congenital malformations, infant colics and food allergies. An active search for symptoms and signs of alarm is recommended. In their absence the performance of an endoscopic study is low. The use of celiac disease serology is also recommended, but the use of fecal calprotectin has the limitation that normal values are not present below age 4, so its use is not recommended under that age.

El dolor abdominal y la distensión abdominal fluctuantes sugieren origen gastrointestinal, con múltiples causas. En adultos, los pacientes que cumplen criterios de Roma para Síndrome de Intestino Irritable (SII) tienen una baja probabilidad de neoplasias o enfermedades inflamatorias intestinales (EII). En estos pacientes, es costoefectivo solicitar calprotectina fecal y serología de enfermedad celiaca. Por la alta probabilidad de efecto nocebo, el diagnóstico de sensibilidad al gluten no celiaca (SGNC) y alergias alimentarias debería requerir un rechallenge ciego. Es recomendable evaluar otras opciones diagnósticas no ominosas en una segunda etapa, si no hay buen control sintomático. En adultos que no cumplen criterios de SII o en adultos mayores de 50 años, suele requerirse más cantidad de estudios, incluyendo endoscópicos. En niños, el dolor abdominal y distensión ocurren frecuentemente en el contexto de consumo excesivo de azúcares (incluyendo fructosa, lactosa y sorbitol). En lactantes puede ocurrir también en el contexto de malformaciones congénitas, cólicos del lactante y alergia alimentaria. Se recomienda la búsqueda activa de signos y síntomas de alarma. En su ausencia el rendimiento del estudio endoscópico es bajo. También se recomienda el uso de serología de enfermedad celíaca, pero el uso de calprotectina fecal tiene la limitación de ausencia de valores de normalidad hasta los 4 años, por lo que su uso no se recomienda bajo esa edad.

Intestinal fructose malabsorption is associated with increased lactulose fermentation in the intestinal lumen / Má absorção intestinal de frutose associa-se com maior fermentação de lactulose na luz intestinal

Abstract Objective: To study fructose malabsorption in children and adolescents with abdominal pain associated with functional gastrointestinal disorders. As an additional objective, the association between intestinal fructose malabsorption and food intake, including the estimated fructose consumption, weight, height, and lactulose fermentability were also studied. Methods: The study included 31 patients with abdominal pain (11 with functional dyspepsia, 10 with irritable bowel syndrome, and 10 with functional abdominal pain). The hydrogen breath test was used to investigate fructose malabsorption and lactulose fermentation in the intestinal lumen. Food consumption was assessed by food registry. Weight and height were measured. Results: Fructose malabsorption was characterized in 21 (67.7%) patients (nine with irritable bowel syndrome, seven with functional abdominal pain, and five with functional dyspepsia). Intolerance after fructose administration was observed in six (28.6%) of the 21 patients with fructose malabsorption. Fructose malabsorption was associated with higher (p < 0.05) hydrogen production after lactulose ingestion, higher (p < 0.05) energy and carbohydrate consumption, and higher (p < 0.05) body mass index z-score value for age. Median estimates of daily fructose intake by patients with and without fructose malabsorption were, respectively, 16.1 and 10.5 g/day (p = 0.087). Conclusion: Fructose malabsorption is associated with increased lactulose fermentability in the intestinal lumen. Body mass index was higher in patients with fructose malabsorption.

Resumo Objetivo: Pesquisar a má absorção de frutose em crianças e adolescentes com dor abdominal associada com distúrbios funcionais gastrintestinais. Como objetivo adicional, estudou-se a relação entre a má absorção intestinal de frutose e a ingestão alimentar, inclusive a estimativa de consumo de frutose, o peso e a estatura dos pacientes e a capacidade de fermentação de lactulose. Métodos: Foram incluídos 31 pacientes com dor abdominal (11 com dispepsia funcional, 10 com síndrome do intestino irritável e 10 com dor abdominal funcional). O teste de hidrogênio no ar expirado foi usado para pesquisar a má absorção de frutose e a fermentação de lactulose na luz intestinal. O consumo alimentar foi avaliado por registro alimentar. Foram mensurados também o peso e a estatura dos pacientes. Resultados: Má absorção de frutose foi caracterizada em 21 (67,7%) pacientes (nove com síndrome do intestino irritável, sete com dor abdominal funcional e cinco com dispepsia funcional). Intolerância após administração de frutose foi observada em seis (28,6%) dos 21 pacientes com má absorção de frutose. Má absorção de frutose associou-se com maior produção de hidrogênio após ingestão de lactulose (p < 0,05), maior consumo de energia e carboidratos (p < 0,05) e maior valor de escore z de IMC para a idade (p < 0,05). As medianas da estimativa de ingestão diária de frutose pelos pacientes com e sem má absorção de frutose foram, respectivamente, 16,1 e 10,5 g/dia (p = 0,087). Conclusão: Má absorção de frutose associa-se com maior capacidade de fermentação de lactulose na luz intestinal. O índice de massa corporal foi maior nos pacientes com má absorção de frutose.

Celiac Crisis: an unusual presentation of gluten-sensitive enteropathy

Celiac disease (CD)­also known as gluten-sensitive enteropathy­is a chronic, genetically predisposing and autoimmune entity with a wide range of clinical manifestations triggered by gluten ingestion, which affects 1% of the general population. Currently, up to 60% of the diagnosis of CD is in adults due to the atypical course of the disease. The severe acute onset of CD­also called celiac crisis­is very uncommon and is still not well documented in adults. We report the case of a 58-year-old man who presented a 45-day history of subtle-onset diarrhea followed by malabsorption syndrome with progressive weight loss, anasarca, and electrolyte disturbances. The diagnostic work-up included an upper digestive endoscopy, which showed scalloping of the duodenal mucosa with pathological features confirmed on biopsies. Specific antibodies were positive, and a satisfactory clinical response was obtained once a gluten-free diet was started. Celiac crisis is a rare initial presentation of CD characterized by severe diarrhea, dehydration, weight loss, hypoproteinemia, and metabolic and electrolyte disturbances. Although rare, it should be considered in patients with apparently unexplained chronic diarrhea.

Enfermedad por inclusión microvellositaria como causa de diarrea congénita severa: caso clínico / Microvillous inclusion disease as a cause of severe congenital diarrhea: case report

Las diarreas congénitas son patologías graves de baja frecuencia y alta mortalidad. Se manifiestan durante los primeros días o meses de vida con severa diarrea, generando insuficiencia intestinal y dependencia de nutrición parenteral. Se debe sospechar ante un recién nacido o lactante con pérdidas masivas hidroelectrolíticas, y se diagnostican utilizando parámetros clínicos, endoscópicos, histológicos y eventualmente genéticos. El tratamiento es de soporte, con reposición hidroelectrolítica intensa y nutricional. OBJETIVO: Presentar un caso de diarrea congénita, identificada como Enfermedad por Inclusión Microvellositaria, de presentación neonatal. CASO CLÍNICO: Paciente varón edad actual 3 años, hijo de padres consanguíneos, quien debutó a los 10 días de vida con diarrea secretora severa, requiriendo ingreso a unidad de paciente crítico y nutrición parenteral permanente. Inicialmente además con síndrome de Fanconi, que luego se recupera. Se confirmó la sospecha de Enfermedad de Inclusión Microvellositaria utilizando microscopia óptica, electrónica e inmunohistoquímica. Se obtuvo una favorable evolución utilizando nutrición parenteral total (NPT) a domicilio. CONCLUSIONES: Se presenta el primer caso conocido en Chile de un paciente con diarrea congénita por inclusión microvellositaria manejado y su evolución.

Congenital diarrheas correspond to a severe and low frequency digestive disease, with a high mortality. They start a few days or months after birth, leading to intestinal insufficiency and dependence on parenteral nutrition. It must be highly suspected in newborns or infants with diarrhea and severe electrolyte disorders. The diagnosis is based on clinical, endoscopic, histologic and eventually genetic findings. Treatment is supportive with intensive correction of electrolyte imbalances as well as parenteral nutrition. OBJECTIVE: To present a case report of congenital diarrhea identified as microvillous inclusion disease presenting in the neonatal period. CASE REPORT: Male patient currently 3 years of age, son of consanguineous parents. At 10 days of age presents a severe secretory diarrhea, requiring treatment in a critical care unit and parenteral nutrition. Initially he also presented with Fanconi syndrome, which improved afterwards. The suspicion of congenital microvillous inclusion was confirmed later by optic and electronic microscopy, and inmunohistochemistry. A succesful evolution was later achieved maintaining home parenteral nutrition after discharge. CONCLUSION: We present the first known case in Chile of congenital diarrhea due to microvillous inclusión disease and his evolution.

A case of celiac disease with neurologic manifestations misdiagnosed as amyotrophic lateral sclerosis

Celiac disease (CD) is an immune-mediated enteropathy and is a rare disease in Asia, including in Korea. However, the ingestion of wheat products, which can act as a precipitating factor of CD, has increased rapidly. CD is a common cause of malabsorption, but many patients can present with various atypical manifestations as first presented symptoms, including anemia, osteopenia, infertility, and neurological symptoms. Thus, making a diagnosis is challenging. We report a case of CD that mimicked amyotrophic lateral sclerosis (ALS). The patient was a sexagenary man with a history of progressive motor weakness for 2 years. He was highly suspected as having ALS. During evaluation of his neurological symptoms, esophagogastroduodenoscopy (EGD) was performed because he had experienced loose stools and weight loss for the previous 7 months. On EGD, the duodenal mucosa appeared smooth. A biopsy revealed severe lymphoplasma cell infiltration with flattened villi. His serum endomysial antibody (immunoglobulin A) titer was 1:160 (reference, <1:40). Finally, he was diagnosed as having CD, and a gluten-free diet was immediately begun. At a 4-month follow-up, his weight and the quality of his stool had improved gradually, and the neurological manifestations had not progressed.

Clinical features and MYO5B mutations of a family affected by microvillus inclusion disease / 中国当代儿科杂志

Microvillus inclusion disease (MVID) is an autosomal recessive disorder caused by biallelic mutations in the MYO5B or STX3 gene. Refractory diarrhea and malabsorption are the main clinical manifestations. The aim of this study was to investigate the clinical features and MYO5B gene mutations of an infant with MVID. A 21-day-old female infant was referred to the hospital with the complaint of diarrhea for 20 days. On physical examination, growth retardation of the body weight and length was found along with moderately jaundiced skin and sclera. Breath sounds were clear in the two lungs and the heart sounds were normal. The abdomen was distended and the veins in the abdominal wall were observed. The liver and spleen were not palpable. Biochemical analysis revealed raised serum total bile acids, bilirubin, transaminases and γ-glutamyl transpeptidase while decreased levels of serum sodium, chloride, phosphate and magnesium. Blood gas analysis indicated metabolic acidosis. The preliminary diagnosis was congenital diarrhea, and thus parenteral nutrition was given along with other symptomatic and supportive measures. However, diarrhea, metabolic acidosis and electrolyte disturbance were intractable, and the cholestatic indices, including transaminases, γ-glutamyl transpeptidase, bilirubin and total bile acids, remained at increased levels. One month later, the patient was discharged and then lost contact. On genetic analysis, the infant was proved to be a compound heterozygote of the c.310+2Tdup and c.1966C>T(p.R656C) variants of the gene MYO5B, with c.310+2Tdup being a novel splice-site mutation. MVID was thus definitely diagnosed.

Eficacia y seguridad del uso de colestiramina en el tratamiento de diarrea cronica con malabsorción de acidos biliares / Efficacy and safety of the use of cholestyramine in the treatment of chronic diarrhea with bile acid malabsorption

INTRODUCCIÓN: Antecedentes: El presente dictamen presenta la evaluación de la eficacia y seguridad del uso de colestiramina en el tratamiento de diarrea crónica asociada a malabsorción de ácidos biliares en niños. Aspectos Generales: La diarrea crónica es el signo principal de la malabsorción de ácidos biliares (MAB), la cual se produce por un desbalance en la homeostasis de estos ácidos en la circulación enterohepática. Los ácidos biliares recirculan entre el hígado y el intestino delgado a través del sistema de circulación enterohepática. Este sistema permite la absorción de grasas en el intestino delgado y la reabsorción de los ácidos biliares en el íleon terminal. Tecnología Sanitaria de Interés: La colestiramina es un secuestrador de ácidos liliares. Esta consta de resinas no digeribles cargadas positivamente que se unen a los ácidos biliares en el intestino, y permiten su excreción en las heces en forma de complejos insolubles. Así, evita que los ácidos biliares se acumulen en el colon y provoquen desbalance hídrico y diarrea. METODOLOGIA: Estrategia de Búsqueda: Se llevó a cabo una busqueda de la literatura con respecto a la eficacia y seguridad de colestiramina en el tratamiento de diarrea crónica en la bases de datos de PubMed, Tripdatase y www.clinicaltrials.gov. RESULTADOS: Sinopsis de la Evidencia: Se llevó a cabo una búsqueda de evidencia científica relacionada al uso de colestiramina en el tratamiento de pacientes con diarrea crónica asociada a malabsorción de ácidos biliares. En la presente sinopsis se describe la evidencia disponible según el tipo de publicación, siguiendo lo indicado en los criterios de elegibilidad (Guias de Práctica Clínica, Evaluación de Tecnologías en Salud, Revisiones Sistemáticas, Resúmenes de Artículos, MA, ECA fase III). CONCLUSIONES: A la fecha (octubre 2016) no se han llevado a cabo ensayos clínicos aleatorizados que evalúen la eficacia y seguridad del uso de colestiramina en pacientes pediátricos o adultos con diarrea crónica ocasionada por la malabsorción de ácidos biliares. Los resultados reportados en el presente dictamen preliminar corresponden a cuatro GPC, una revisión sistemática basada en estudios observacionales y el resumen de un estudio retrospectivo que evalúa la respuesta al tratamiento con colestiramina en pacientes adultos con diarrea crónica acuosa. El Instituto de Evaluación de Tecnologias en Salud e Investigación (IETSI) aprueba el uso de colestiramina como alternativa de tratamiento en pacientes con diarrea crónica por ácidos biliares. En el periodo de vigencia de este dictamen es de un año y la continuación de dicha aprobación estará sujeta a los resultados obtenidos de los pacientes que se beneficien con dicho tratamiento y a nueva evidencia que pueda surgir en el tiempo.

Detection of enteric viruses in pancreas and spleen of broilers with runting-stunting syndrome (RSS) / Detecção de vírus entéricos em pâncreas e baço de frangos com a síndrome de nanismo e raquitismo (RSS)

Enteric disease is a multifactorial problem in chickens, which causes gastrointestinal alterations, elevated feed conversions and impairment. In the last years, several enteric viruses were implicated in enteric disease; case reports have shown their presence alone or in concomitant infections during outbreaks and have suggested that they might be determining factors in the aetiology of enteric disease. This study shows high detection rates of enteric viruses in the pancreas and spleen in samples from an outbreak of enteritis and malabsorption in 16 chicken flocks (n=80 broilers). Avian nephritis virus (ANV) was the most ubiquitous virus, present in 75% of the flocks followed by avian rotavirus group A (ART-A) with 68.75%, and by chicken astrovirus (CAstV) and chicken parvovirus (ChPV) in 43.75% of samples. Viruses were present in the pancreas of positive flocks at extremely high rates: 100% for ART-A, 91.7% for ANV, 100% for CAstV and 57.14% for ChPV. By contrast, only 16.7% and 57.14% of intestine samples were positive for ANV and CAstV, respectively. Avian reovirus (AReo) and avian adenovirus group 1 (FAdV-1) were not detected. These results suggest that high viral detection rates in pancreas samples may be a result of viremia during enteric disease, with subsequent damage of the exocrine pancreas, leading to runting-stunting syndrome (RSS).(AU)

A doença entérica é um problema multifatorial em galinhas que causa alterações gastrointestinais, conversão alimentar elevada e deficiência de crescimento. Nos últimos anos, os vírus entéricos foram associados à doença entérica; casos reportados mostraram a infecção de um único vírus e também infecções concomitantes durante os surtos sugerindo a presença de múltiplos fatores etiológicos nas doenças entéricas. Este estudo mostra uma alta taxa de detecção dos vírus entéricos em amostras de pâncreas e baço de um surto de enterite e má-absorção em 16 lotes de frangos (n=80 frangos). O vírus de nefrite aviária (ANV) foi o vírus mais detectado, estando presente em 75% dos lotes seguido pelo rotavírus aviário grupo A (ART-A) em 68,75% dos casos, e pelo astrovirus (CAstV) e parvovírus aviários (ChPV), ambos em 43,75% das amostras. Os vírus estavam presentes no pâncreas dos lotes positivos em percentuais elevados: 100% para ART-A e CAstV; 91,7% para ANV, e em 57,14% para ChPV. Em contraste, somente 16,7% e 57,14%, em amostras de intestino, foram positivos para ANV e CAstV, respectivamente. Reovírus aviário (AReo) e o adenovírus do grupo 1 (FAdV-1) não foram detectados. Estes resultados sugerem que os elevados percentuais de vírus detectados em amostras de pâncreas podem estar associados à viremia durante a doença entérica, com subsequente lesão no pâncreas exócrino das aves levando ao desenvolvimento da síndrome de nanismo e raquitismo.(AU)

Phenotypic and genetic analysis of a family affected with microvillus inclusion disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the clinical features and mutations of MYO5B gene in a family affected with microvillus inclusion disease.</p><p><b>METHODS</b>Clinical data of an infant affected with microvillus inclusion disease was collected. Genomic DNA was extracted from peripheral blood samples from the patient and her parents. PCR amplification and Sanger sequencing were performed to analyze all the exons and their flanking sequences of the MYO5B gene.</p><p><b>RESULTS</b>The patient presented with complicated manifestations including respiratory distress syndrome, dehydration, acidosis, bowel dilatation, liver and kidney dysfunction, and severe and intractable diarrhea. A compound mutation of the MYO5B gene, i.e., IVS37-1G>C/c.2729_2731delC (p.R911Afs916X), was discovered in the patient. The former was a splice-site mutation inherited from the mother, while the latter was a frameshift mutation inherited from the father. Both were not reported previously.</p><p><b>CONCLUSION</b>Based on the clinical and molecular evidence, the patient was diagnosed with microvillus inclusion disease. Above finding has expanded the mutation spectrum of the MYO5B gene, which can provide valuable information for genetic counseling for the family.</p>

Enfermedad celíaca, ¿qué hay de nuevo? / Celiac disease, what's new?

La enfermedad celíaca (EC) es una enteropatía autoinmune sensible al gluten, con base genética. La prevalencia de la enfermedad es elevada y conforme aumentan los conocimientos de la patología, aumenta la prevalencia. Es bien conocida la asociación entra la EC y otras enfermedades de origen autoinmunitario. Los síntomas clásicos aparecen secundariamente a la malabsorción intestinal y desaparecen al retirar el gluten de la dieta, si bien el espectro clínico es muy amplio, con síntomas extradigestivos muy variados, lo que da una idea de que es una enfermedad multisistémica. El diagnóstico se realiza mediante biopsia intestinal y los marcadores serológicos. Su único tratamiento consiste en una dieta estricta sin gluten mantenida indefinidamente, ya que sin respetarse la dieta, podría evolucionar una complicación potencial más grave, que es la malignización

Celiac disease is an autoimmune gluten-sensitive enteropathy, with a genetic basis. The prevalence of the disease is high and increases as the knowledge of the disease. It is well known the association enters the EC and other diseases of autoimmune origin. The classic symptoms occur secondary to intestinal malabsorption and disappear when removing gluten from the diet, although the clinical spectrum is very broad, with varied symptoms extradigestive, which gives an idea that is a multisystem disease. The diagnosis is made by intestinal biopsy and serological markers. The only treatment is a strict gluten-free diet, if there is no adherence to the diet could evolve a more serious potential complication, which is malignant

Eosinophilic gastroenteritis which leads to mal-absorption and anemia associated with food allergies

Eosinophilic gastroenteritis (EG) is a rare disease characterized by massive eosinophilic infiltration of gastrointestinal tissue, peripheral eosinophilia, and nonspecific gastrointestinal symptoms. The mucosal type of EG commonly presented with malabsorption and anemia. However, the role of food allergy as a stimulus to EG has not yet been clearly defined. A 27-year-old man was referred to the Emergency Department with dyspepsia and leg swelling. The initial laboratory test should as follows: hemoglobin level, 6.4 g/dL; white blood cell count, 7,400/microL with 24.4% of eosinophil fraction; serum total protein, 3.9 g/dL; albumin level, 2.8 g/dL. Gastric endoscopy ruled out gastrointestinal bleeding showed multiple nodular raised lesions on the gastric antrum, which revealed increased eosinophilic infiltration (above 100/high power field). He had experienced nausea whenever eating beef, porks or fish. High serum specific IgE levels to offending foods (beef, 0.82 kU/L; pork, 0.83 kU/L; egg white, 0.40 kU/L; egg yolk, 0.54 kU/L; milk, 0.81 kU/L) were noted. He was instructed strictly to avoid food allergens with oral prednisolone therapy. Approximately 6 months after offending food restriction, the eosinophil count fell down to 400/microL, the hemoglobin level was returned to 11.5 g/dL and the serum albumin level was increased to 4.1 g/dL. We report a case of EG caused by multiple food allergy which leads to malabsorption and iron-deficiency anemia.

Disorders associated with malabsorption of iron: a critical review

Malabsorption is a disorder of the gastrointestinal tract that leads to defective digestion, absorption and transport of important nutrients across the intestinal wall. Small intestine is the major site where most of the nutrients are absorbed. There are three main mechanisms of malabsorption; premucosal, mucosal and postmucosal. Premucosal malabsorption is the inadequate digestion due to improper mixing of gastrointestinal enzymes and bile with chyme. This could be because of surgical resection of the small intestine or a congenital deficiency of the enzymes and bile responsible for digestion e.g. postgastrectomy, chronic pancreatitis, pancreatic cancer, cystic fibrosis, gallstones, cholangitis etc. Mucosal malabsorption occurs in celiac disease, tropical sprue, Crohn's disease etc. Postmucosal condition arises due to impaired nutrients transport e.g. intestinal lymphangiectasia, macroglobulinemia etc. Disorders of malabsorption lead to decreased iron absorption and produce iron deficiency anemia. Using the index terms malabsorption, postgastrectomy, chronic pancreatitis, pancreatic cancer, cystic fibrosis, gallstones, cholangitis, celiac disease, tropical sprue, Crohn's disease intestinal lymphangiectasia, macroglobulinemia and iron deficiency anemia the MEDLINE and EMBASE databases were searched. Additional data sources included bibliographies and references of identified articles

Manifestaciones dermatológicas relacionadas con la exposición al gluten: revisão / Dermatological manifestations related with gluten exposure. a review

Los desórdenes asociados con la exposición al gluten incluyen entidades que difieren en la fisiopatogenia, la clínica y el diagnóstico, pero comparten el mismo factor ambiental desencadenante (gluten) y, en consecuencia, el tratamiento (dieta libre de gluten). Se pueden clasificar en procesos autoinmunes, mediados principalmente por linfocitos T helper 2 e IgA; alérgicos,mediados por Linfocitos T helper 1 e IgE; y procesos no autoinmunes ni alérgicos, posiblemente mediados por una respuesta inmunológica innata. Las manifestaciones dermatológicas de dichos desórdenes son muy variadas, por lo que es fundamental su conocimiento por parte de los dermatólogos, a fin de realizar un diagnóstico temprano.

Disorders associated with gluten exposure include entities differing in pathogenesis, clinical and diagnosis, but sharing the same environmental trigger (gluten) and, consequently, treatment options (gluten-free diet). They can be classified in autoimmune processes, mediated primarily by T helper 2 lymphocytes and Ig A; allergic processes, mediated by T helper 1 lymphocytes and Ig E; and non-autoimmune or allergic processes, probably mediated by an innate immune response. Dermatological manifestations of these disorders are varied, so it is essential knowledge by dermatologists to make an early diagnosis.