Síndrome de Cohen: reporte de caso y revisión de la literatura / Cohen syndrome: case report and literature review

Resumen Introducción: el Síndrome de Cohen es una enfermedad genética monogénica autosómica recesiva, que se origina a partir de mutaciones en el gen VPS13B (COH1). Se caracteriza por obesidad, retraso psicomotor, microcefalia, hipotonía, miopía progresiva, distrofia retiniana, neutropenia intermitente y rasgos faciales particulares. Objetivo: presentar el segundo caso reportado en Colombia, que fue confirmado mediante estudio molecular. También se presenta una breve revisión de la literatura médica más reciente sobre esta patología. Caso clínico: adolescente de 14 años con microcefalia, trastorno cognitivo, malformaciones menores asociadas, neutropenia y obesidad, con mutación homocigota del gen VPS13B. Conclusión: a pesar de ser un síndrome poco común, con importante variabilidad fenotípica, debe sospecharse con base en los criterios clínicos y en las patologías asociadas.

Abstract Introduction: cohen's syndrome is an autosomal recessive monogenic genetic disease, which originates from mutations in the VPS13B (COH1) gene. It is characterized by obesity, psychomotor retardation, microcephaly, hypotonia, progressive myopia, retinal dystrophy, intermittent neutropenia, and classic facial features. Objective: to present the second case reported in Colombia, which was confirmed by molecular study. A brief review of the most recent medical literature on this pathology is also presented. Clinical case: a 14-year-old adolescent with microcephaly, cognitive disorder, minor associated malformations, neutropenia, and obesity, with a homozygous VPS13B gene mutation. Conclusion: despite being a rare syndrome, with significant phenotypic variability, it should be suspected based on clinical criteria and associated pathologies.

Complex Congenital Heart Disease and Neurodevelopment. A Case Study of Fraternal Twins.

Congenital heart defects have been associated with adverse neurodevelopmental outcomes due to factors that result in a hypoxic-ischemic cerebral cumulative effect. We present a pair of fraternal twins: the first twin was healthy, and the second was born with a complex congenital heart defect (CCHD). They were followed for growth and neurodevelopmental outcomes to determine the comparative effect of exposure to a CCHD. Results show that exposure to a CCHD could be related to a persistent motor deficiency with hypotonia and concurrent height for age delay. CCHD requires a comprehensive neurodevelopmental approach; the pathophysiology and the surrounding stimuli are influential.

Neurodevelopmental outcome of infants without central nervous system anomalies born to symptomatic RT-PCR ZIKV positive women.

An epidemic of Zika virus (ZIKV) infection began in Colombia in October 2015. Previous studies have identified a cause-effect relationship between fetal exposure to the ZIKV and the development of microcephaly and other central nervous system (CNS) anomalies with variable degrees of neurodevelopmental delay. Less is known about the neurodevelopmental outcome of infants without CNS anomalies born to symptomatic ZIKV RT-PCR-positive women. We aimed to compare the neurodevelopmental outcome of these infants to a control group of infants without CNS anomalies born to asymptomatic ZIKV RT-PCR negative women who did not seroconvert during pregnancy. Participating infants were categorized according to ZIKV maternal exposure. Women with symptomatology suggestive of ZIKV infection and a positive RT-PCR for ZIKV were categorized as ZIKV-exposed. Maternal controls (ZIKV unexposed) from the same geographic area were subsequently captured during the tail end of the epidemic through a partner project, the ZIKAlliance, whose aim was to determine the prevalence of ZIKV in pregnant women. Infant survivors from these two groups of pregnant women had a neurodevelopmental evaluation at 12, 18, and 24 months corrected age (CA). The ZIKV-exposed women were found to be older, had less subsidized health care, had a higher percentage of women in middle-class socioeconomic strata, had higher technical and university education, were less likely to be living with a partner, and had higher rates of pregnancy comorbidity and premature births than ZIKV unexposed women. Compared to infants born to ZIKV unexposed women (unexposed), infants born to ZIKV exposed women (exposed) were of lower gestational age and required more speech and occupational therapy services. No differences between groups were observed in the proportion of cut-off scores <70 on the Bayley-III Scale at 12, 18, and 24 months for motor, language, and cognitive domains. When a cut-off of <85 was used, a higher percentage of motor and cognitive impairment was observed in unexposed infants at 12 and 24 months CA, respectively. Median and IQR score on the Bayley-III scale showed higher scores in favor of exposed infants for motor development at 12 and 18 months CA, language at 12 months, and cognitive domain at 12, 18, and 24 months. The adjusted median and IQR compound score of the difference between exposed and unexposed was higher in favor of exposed infants at 12 to 24 months CA for motor (3.8 [95% CI 1.0 to 6.7]) and cognitive domains (10.6 [95% CI 7.3 to 13.9]). We observed no differences in the language domain (1.9 [95% CI -1.2 to 5.0]). We conclude that infants with no evidence of microcephaly or other CNS anomalies born to ZIKV-exposed women had normal neurodevelopment up to 24 months of CA, supporting an all-or-nothing effect with maternal ZIKV exposure. Long-term follow-up to evaluate school performance is required. Clinical Trial Registration: www.clinicaltrials.gov, NCT02943304.

Fetal central nervous system anomalies according to RT-PCR and trimester of maternal infection with Zika virus: A prospective cohort study.

INTRODUCTION: In October 2015, an epidemic of Zika began in Colombia's geographic areas with a high population of mosquitoes of the genus Aedes. We aimed to describe the fetal brain ultrasound findings in pregnant women with active symptoms or a history of symptoms suggestive of Zika virus (ZIKV) infection. MATERIAL AND METHODS: Eligible pregnant women were tested with reverse transcriptase-polymerase chain reaction (RT-PCR) for ZIKV and followed prospectively using detailed anatomic ultrasound and transvaginal neurosonography to detect structural anomalies of the fetal central nervous system (CNS). RESULTS: A total of 115 symptomatic women with a positive ZIKV RT-PCR and 55 with a negative ZIKV RT-PCR were enrolled in the study; CNS compromise of the fetus occurred in 22% and 17%, respectively (p = 0.255). Callosal dysgenesis (14.5%) was the most frequent anomaly of the CNS, followed by microcephaly (13.6%) and neuronal migration disorders (8.3%). When symptomatic ZIKV RT-PCR-positive women were categorized by trimester of infection, CNS anomalies were present in 40% of first-trimester infections, compared with 21% and 7% in second- and third-trimester infections (p = 0.002). CNS anomalies were also more severe in first-trimester-infected fetuses than in second- and third-trimester-infected fetuses. The high prevalence of CNS anomalies in fetuses of symptomatic ZIKV RT-PCR negative women suggests a high rate of false-negative cases and an even higher prevalence of CNS anomalies than observed in this study. CONCLUSIONS: The prevalence of fetal CNS anomalies was higher than previously reported in the literature for both symptomatic RT-PCR-positive and -negative pregnant women. Corpus callosum anomalies, microcephaly, neuronal migration disorders, and brain parenchymal hyperechogenicities were the most frequent CNS anomalies detected. In addition, CNS anomalies were more frequent and severe in infected fetuses during the first trimester of pregnancy than during the second or third trimester.

45,X/46,XY Mosaicism with Male Phenotype: Case Report.

Mixed gonadal dysgenesis is the most common chromosomal abnormality with ambiguous genitalia, defined as a 45,X/46,XY mosaicism. It can present with a normal male phenotype, ambiguous genitalia, or features of Turner syndrome. A 14-year-old patient was referred to the genetics clinic due to hypospadia, cryptorchidism, and aortic coarctation. During the physical examination, short stature, webbed neck, and Blashko lines on his back were noted. He had a previous karyotype reported as normal. However, due to an inadequate evolution and a low resolution on the previous test, a higher resolution karyotype was performed, identifying a mosaicism 45,X/46,XY. A multidisciplinary board examined the case, and follow-up with tumor markers was carried out to evaluate the presence of gonadoblastoma, one of the main complications in these patients. Treatment should be transdisciplinary and focused on the particular characteristics of each case. Other treatment alternatives include corrective surgery and hormonal therapy.

Síndrome nefrótico congénito. Reporte de caso y revisión del enfoque diagnóstico / Congenital nephrotic syndrome. Case report and review of its diagnostic work up

Resumen El síndrome nefrótico se define como la unión de proteinuria masiva, hipoalbuminemia e hiperlipidemia, que pueden asociarse a edemas e hipercoagulabilidad. Se origina de una anormalidad de la barrera de filtración glomerular con una fuga masiva de proteína y los efectos secundarios consecuentes. En sus formas primarias, ocurre con una incidencia de 1-3 por cada 100.000 niños menores de 16 años. La forma congénita es una variante poco frecuente del síndrome nefrótico, la cual se presenta en el nacimiento o dentro de los tres primeros meses de vida, y suele ser resistente a la corticoterapia. Se debe evaluar primero la existencia de infecciones congénitas y luego buscar las enfermedades monogénicas más comunes, finalmente se puede recurrir a la secuenciación de nueva generación para buscar mutaciones en los demás genes candidatos. Se presenta el caso de una niña con síndrome nefrótico congénito de difícil control, enfatizando en el proceso diagnóstico y el manejo de soporte. Se resalta la importancia de la asesoría genética a la familia en todos los casos.

Abstract A nephrotic syndrome is defined as the association of massive proteinuria, hypoalbuminemia and hyperlipidemia, which may be associated with edema and hypercoagulability. It originates from an abnormality of the glomerular filtration barrier with a massive protein leak and the consequent side effects. In its primary forms, it occurs with an incidence of 1 - 3 per 100,000 children under 16 years of age. The congenital form is a rare variant of the nephrotic syndrome, which occurs at birth or within the first three months of life and is usually resistant to corticosteroid therapy. Congenital infections and most common related monogenic diseases should be tested. Finally, new generation sequencing must be used to search for mutations in other candidate genes. We present the case of a girl with congenital nephrotic syndrome difficult to control, emphasizing the diagnostic process and support management. The importance of genetic counseling to the family in all cases is highlighted.

Síndrome de Rett: revisión de la literatura con primeros casos reportados en Colombia con caracterización clínica y molecular / Rett syndrome: review of the literature and first cases reported in Colombia with clinical characterization and molecular diagnosis

RESUMEN INTRODUCCIÓN: El síndrome de Rett es una condición neurológica severa y la segunda causa genética de retraso mental profundo en mujeres. Se genera por mutaciones en el gen MECP2 y es caracterizada por una pérdida de las ganancias psicomotoras, con una prevalencia general estimada de 1:10.000 niñas, según la extrapolación de algunos estudios europeos. OBJETIVOS: Realizar una revisión de la literatura sobre el síndrome de Rett y presentar una serie de casos diagnosticados en Colombia por clínica y prueba molecular. METODOLOGÍA: Se efectuó una búsqueda bibliográfica y de reportes de casos en 21 bases de datos internacionales, más de 14 revistas del área de la salud y dos motores de búsqueda generales entre 2014 y 2016. Los casos presentados fueron seleccionados de la consulta de genética médica realizada por los autores. HALLAZGOS: No se encontró ningún caso colombiano de síndrome de Rett, ni confirmado con prueba molecular en Latinoamérica. Se reporta así la primera serie de casos nacional y la mayor latinoamericana, conformada por siete pacientes con tipo clásico y tres atípicos, todas con diagnóstico molecular. CONCLUSIONES: Pese a tener una evolución clínica caracterizada, su baja prevalencia y amplio espectro clínico convierten al síndrome de Rett en un reto diagnóstico y terapéutico. La mutación c.749_750insT se reporta por primera vez, la c.473C>G por segunda en la literatura y la c.763C>T se presenta en dos pacientes con fenotipos totalmente distintos, lo que confirma la no correlación genotipo-fenotipo de la enfermedad.

SUMMARY INTRODUCTION: Rett Syndrome is a severe neurological condition and the second genetic cause of profound mental retardation in women. It is generated by mutations in the MECP2 gene and it is characterized by a loss of psychomotor gains, with an estimated overall prevalence of 1:10,000 girls, according to the extrapolation of some European studies. Objectives. To make a review of Rett Syndrome and to present a series of cases diagnosed in Colombia by clinical criteria and molecular tests. METHODOLOGY: We made a bibliographic research in 21 international databases, more than 14 health journals and two general search engines between 2014 and 2016. The cases presented were selected from the Medical Genetics consultation carried out by the authors. FINDINGS: No Colombian case of Rett Syndrome was found nor confirmed with molecular testing in Latin America. We report the first cases in Colombia and the largest in Latin America, consisting of seven patients with classic type and three with atypical type, all with molecular diagnosis. CONCLUSIONS: In spite of having a characterized clinical evolution, its low prevalence and broad clinical spectrum, make Rett Syndrome a diagnostic and therapeutic challenge. We report for the first time the mutation c.749_750insT, the c.473C> G for second time in the literature and the c.763C> T is presented in two patients with totally different phenotypes, confirming the non-correlation genotype-phenotype of the disease.

17-hydroxyprogesterone levels in blood from the heels of healthy full-term newborns / Niveles de 17 - hidroxiprogesterona en sangre de talón de neonatos a término sanos

Abstract Background and aim: Congenital adrenal hyperplasia is caused by enzymatic abnormalities in the synthesis of adrenal steroids. A pilot study was carried out to measure the values of 17- hydroxyprogesterone (17-OHP) in a sample of healthy full-term newborns; the present study aims to determine if birth weight or gender have differences on 17-OHP. Design: Transversal, descriptive, and prolective study. Methods: We included 81 healthy full-term newborns with normal prenatal controls born between July 18th, 2014, and August 1st, 2015. We took whole blood from heel pricks when the babies were three to five days old. Socioeconomic and clinical data were collected. Non-extracted 17-OHP ELISA was used. Its cut-off point was 20 ng/ml. If results were above cut-off point, babies were recalled for a new measure since transient high 17-hydroxyprogesterone levels are possible until babies are three months of age. Results: Gestational age varied between 37.0 to 41.5 weeks. Non-extracted 17-OHP levels ranged between 2.6 to 29.5 ng/mL (median: 11.5, IQR 7.2 to 15.1). 17-OHP levels variation per birth weight or gender were not found. Conclusions: Expected lesser variation in term newborns may explain these results. Quality issues should be solved before starting a screening program in our population because socioeconomic issues cause most problems in recalling positive screening babies.

Resumen Justificación: la hiperplasia adrenal congénita es una enfermedad autosómica recesiva ocasionada por anormalidades enzimáticas en la síntesis de los esteroides adrenales. Se realizó un estudio para medir los valores de 17- hidroxiprogesterona en una muestra de neonatos a término sanos. El objetivo fue conocer si existían diferencias en el valor de 17-OHP según edad gestacional y sexo. Diseño: estudio transversal, descriptivo y prolectivo. Métodos: se incluyeron 81 neonatos con controles prenatales normales y nacidos entre julio 18 de 2014 y agosto 1 de 2015. Se obtuvieron muestras de sangre del talón cuando los bebés tenían entre tres a cinco días de vida. Se recolectaron datos socioeconómicos y clínicos. Se utilizó un ELISA de 17-OHP no extraída. El punto de corte de la prueba de ELISA de 17-OHP fue 20 ng/mL. Si los resultados estaban por encima del valor de corte, se citaron los bebés para una nueva medición, dado que es posible hallar una hiper 17-hidroxiprogesteronemia hasta los tres meses de edad. Resultados: la edad gestacional varió entre 37 a 41,2 semanas. Los valores de 17-OHP no extraída variaron entre 2,6 a 29,5 ng/mL (mediana 11,5 y RIQ 7,2 - 15,1). Los niveles de 17-OHP no variaron según peso al nacer o sexo. Conclusión: estos resultados se podrían explicar por una menor variación esperada en neonatos a término. Se deben resolver algunos problemas de calidad antes de poder empezar un programa de tamizaje en nuestra población, debido a que causas socioeconómicas generaron dificultad al reevaluar los niños con resultados positivos de tamizaje.

17-hydroxiprogesterone values in healthy preterm infants / Valores de 17-hidroxiprogesterona en recién nacidos prematuros sanos

Abstract Introduction: In preterm newborn, problems with the interpretation of 17-OHP may occur. Objective: Evaluate 17-OHP values in healthy preterm newborns until they reach the corrected gestational age. Methods: Longitudinal study of 36 preterm infants with 17-OHP evaluation using ELISA from heel blood from 3 to 5 days and thereafter every 2 weeks until the corrected gestational age. Values adjusting multiple variables such as gestational age, birth weight and sex, among others were compared. The results were analyzed against 82 healthy full-term infants. Results: In the first week of life, early term infants born within less than 34 months of gestational age show 17-OHP values that are much higher than the full term neonates. After a week, the values decrease and stabilize, but are still higher than those of full term neonates and remain so even at the corrected gestational age. (average difference of 63.0%, CI 95%: 11.8%-115.5%). 33.6% (41 samples) of a total of 122 samples taken from preterm infants were higher than 30 ng/mL. Conclusions: 17-OHP values in early term infants are higher than those in full term neonates and can be related to postnatal adaptive processes. It is suggested that a second screening at the 37th week of corrected age be performed.

Resumen Introducción: En recién nacidos pretérmino se presentan problemas para interpretar la 17-OHP. Objetivo: Evaluar los valores de 17-OHP en recién nacidos sanos pretérmino hasta cuando alcanzan el término de edad gestacional corregida. Métodos: Estudio longitudinal de 36 prematuros con evaluación de la 17-OHP por ELISA en sangre de talón desde los 3-5 días de vida y luego cada dos semanas hasta la edad gestacional de término corregida. Se comparó los valores ajustando múltiples variables como edad gestacional, peso al nacer y sexo, entre otras. Se analizaron los resultados frente a los de 82 recién nacidos a término sanos. Resultados: En la primera semana de vida, los prematuros menores de 34 semanas de edad gestacional tienen valores de 17-OHP muy superiores a los neonatos de término. Al alcanzar la semana 34 de edad gestacional corregida, los valores descienden y se mantienen estables, siempre mayores a los de término, incluso al llegar a edad a término corregida (diferencia promedio de 63.0%, IC 95%: 11.8%-115.5%). El 33.6% (41 muestras) de un total de 122 muestras hechas en los prematuros eran mayores de 30 ng/mL. Conclusiones: Los valores de 17-OHP en recién nacidos pretérmino son más altos que en neonatos a término, pudiendo ser relacionado con los procesos adaptativos postnatales. Se sugiere realizar un segundo tamizaje al llegar a la semana 37 de edad corregida.

[Peroxisomal disorder, rhizomelyc chondrodysplasia punctata type 1: case report]. / Enfermedad peroxisomal, condrodisplasia rizomelica punctata tipo 1: reporte de caso.

INTRODUCTION: Peroxisomal diseases are a group of monogenic disorders that include defects in peroxisome biogenesis or enzyme dificiencies. Rhizomelic chondrodysplasia punctata type 1 (RCDP1) belongs to the first group, caused by autosomal recessive mutations on PEX7 gene, encoding for PTS2 receptor. The aims of this report are to describe a genetic disease of low prevalence, explaining its main characteristics and the importance of the diagnostic approach and genetic counseling. CASE REPORT: 13-month-old male infant with no medical history, family or consanguinity, demonstrate at birth upper limbs shortening. Surgery intervention at seven months old for bilateral cataract. Growth retardation, psychomotor retardation, minor craniofacial anomalies, rhyzomelic shortened upper limbs and lower limbs lesser degree. Punctata calcifications in patella cartilage. Also fatty acid phytanic and pristanic increased levels. Patient dead at age of 3 years. DISCUSSION: RCDP1 is a rare disease, with a prevalence of 1/100,000. Different mutations of PEX7 gene have been described, with variations in phenotype. The treatment is basically symptomatic and depends on the severity of clinical manifestations. The rhizomelic type has poor prognosis, most patients do not survive before the first decade of live. Genetic counseling is essential because it is consider a 25% risk of recurrence.

17-hydroxiprogesterone values in healthy preterm infants.

INTRODUCTION: In preterm newborn, problems with the interpretation of 17-OHP may occur. OBJECTIVE: Evaluate 17-OHP values in healthy preterm newborns until they reach the corrected gestational age. METHODS: Longitudinal study of 36 preterm infants with 17-OHP evaluation using ELISA from heel blood from 3 to 5 days and thereafter every 2 weeks until the corrected gestational age. Values adjusting multiple variables such as gestational age, birth weight and sex, among others were compared. The results were analyzed against 82 healthy full-term infants. RESULTS: In the first week of life, early term infants born within less than 34 months of gestational age show 17-OHP values that are much higher than the full term neonates. After a week, the values decrease and stabilize, but are still higher than those of full term neonates and remain so even at the corrected gestational age. (average difference of 63.0%, CI 95%: 11.8%-115.5%). 33.6% (41 samples) of a total of 122 samples taken from preterm infants were higher than 30 ng/mL. CONCLUSIONS: 17-OHP values in early term infants are higher than those in full term neonates and can be related to postnatal adaptive processes. It is suggested that a second screening at the 37th week of corrected age be performed.

INTRODUCCIÓN: En recién nacidos pretérmino se presentan problemas para interpretar la 17-OHP. OBJETIVO: Evaluar los valores de 17-OHP en recién nacidos sanos pretérmino hasta cuando alcanzan el término de edad gestacional corregida. MÉTODOS: Estudio longitudinal de 36 prematuros con evaluación de la 17-OHP por ELISA en sangre de talón desde los 3-5 días de vida y luego cada dos semanas hasta la edad gestacional de término corregida. Se comparó los valores ajustando múltiples variables como edad gestacional, peso al nacer y sexo, entre otras. Se analizaron los resultados frente a los de 82 recién nacidos a término sanos. RESULTADOS: En la primera semana de vida, los prematuros menores de 34 semanas de edad gestacional tienen valores de 17-OHP muy superiores a los neonatos de término. Al alcanzar la semana 34 de edad gestacional corregida, los valores descienden y se mantienen estables, siempre mayores a los de término, incluso al llegar a edad a término corregida (diferencia promedio de 63.0%, IC 95%: 11.8%-115.5%). El 33.6% (41 muestras) de un total de 122 muestras hechas en los prematuros eran mayores de 30 ng/mL. CONCLUSIONES: Los valores de 17-OHP en recién nacidos pretérmino son más altos que en neonatos a término, pudiendo ser relacionado con los procesos adaptativos postnatales. Se sugiere realizar un segundo tamizaje al llegar a la semana 37 de edad corregida.

Enfermedad peroxisomal, condrodisplasia rizomelica punctata tipo 1: reporte de caso / Peroxisomal disorder, rhizomelyc chondrodysplasia punctata type 1: case report

Introducción: Las enfermedades peroxisomales son un grupo de trastornos monogénicos que incluyen desórdenes en la biogénesis del peroxisoma o deficiencias enzimáticas. La Condrodisplasia Rizomélica Punctata Tipo 1 (RCDP1) pertenece al primer grupo, es autosómica recesiva originada por mutaciones del gen PEX7, que codifica para el receptor PTS2. El objetivo del presente artículo son describir una enfermedad genética de baja prevalencia, explicando sus principales características y la importancia de la aproximación diagnóstica y asesoría genética. Caso clínico: Lactante masculino de 13 meses, sin antecedentes familiares ni consanguinidad. Al nacimiento presentaba acortamiento de miembros superiores. Fue intervenido a los 7 meses por catarata bilateral. Presentaba severo retardo del crecimiento, retraso del desarrollo psicomotor, anomalías menores craneofaciales, acortamiento rizomélico de miembros superiores y en menor grado de miembros inferiores. En la radiografía se identificaban calcificaciones punteadas del cartílago en rótula. Entre los exámenes de laboratorio destacaba elevación de los ácidos grasos fitánico y pristánico. El paciente falleció a la edad de 3 años. Discusión: Esta es una enfermedad rara, la prevalencia es 1/100.000, se han descrito diferentes mutaciones del gen PEX7 teniendo variación en el fenotipo. El tratamiento es básicamente sintomático y depende de la gravedad de las manifestaciones clínicas, el tipo rizomélico es de mal pronóstico, la mayoría de los pacientes no sobrevive antes de la primera década de vida. La asesoría genética es fundamental ya que se considera un riesgo del 25% de recurrencia.

Introduction: Peroxisomal diseases are a group of monogenic disorders that include defects in peroxisome biogenesis or enzyme dificiencies. Rhizomelic chondrodysplasia punctata type 1 (RCDP1) belongs to the first group, caused by autosomal recessive mutations on PEX7 gene, encoding for PTS2 receptor. The aims of this report are to describe a genetic disease of low prevalence, explaining its main characteristics and the importance of the diagnostic approach and genetic counseling. Case report: 13-month-old male infant with no medical history, family or consanguinity, demonstrate at birth upper limbs shortening. Surgery intervention at seven months old for bilateral cataract. Growth retardation, psychomotor retardation, minor craniofacial anomalies, rhyzomelic shortened upper limbs and lower limbs lesser degree. Punctata calcifications in patella cartilage. Also fatty acid phytanic and pristanic increased levels. Patient dead at age of 3 years. Discussion: RCDP1 is a rare disease, with a prevalence of 1/100,000. Different mutations of PEX7 gene have been described, with variations in phenotype. The treatment is basically symptomatic and depends on the severity of clinical manifestations. The rhizomelic type has poor prognosis, most patients do not survive before the first decade of live. Genetic counseling is essential because it is consider a 25% risk of recurrence.

Mucopolisacaridosis: características clínicas, diagnóstico y de manejo / Mucopolysaccharidosis: clinical features, diagnosis and management

Las mucopolisacaridosis (MPS) son un grupo de enfermedades raras (huérfanas), de baja prevalencia, caracterizadas por la deficiencia de enzimas que participan en el metabolismo de glucosaminglucanos (GAG) a nivel lisosomal. Se caracteriza por acumulación de GAG intracelular, produciendo alteraciones de múltiples órganos y sistemas. Su diagnóstico se basa en el conocimiento de las manifestaciones clínicas, realizar el análisis bioquímico para identificar el tipo de GAG que se está acumulando y confirmar el tipo de enfermedad con la determinación enzimática correspondiente. Su identificación es fundamental para iniciar un tratamiento oportuno, teniendo en cuenta que actualmente existe manejo transdisciplinario y tratamiento de reemplazo enzimático para MPS I (síndrome de Hurler), MPS II (síndrome de Hunter), MPS IV (síndrome de Morquio) y MPS VI (síndrome de Maroteaux-Lamy). En esta revisión se analizan cada uno de estos síndromes, su diagnóstico y tratamiento.

The mucopolysaccharidoses (MPS) are a group of rare (orphan) diseases, characterised by a deficiency of enzymes involved in the metabolism of glycosaminoglycans (GAGs) at lysosomal level. When there is a deficiency of a particular enzyme there is an accumulation of GAGs in the cells resulting in progressive cellular damage, which can affect multiple organ systems and lead to organ failure. Diagnosis is based on knowledge of the clinical manifestations, performing biochemical analyses to identify the type of GAG that is accumulating, and confirm the type of disorder with the corresponding enzymatic determination. Their identification is essential to initiate early treatment, taking into account that multidisciplinary management and enzyme replacement therapy is available for MPS I (Hurler syndrome), MPS II (Hunter syndrome), MPS IV (Morquio syndrome), and MPS VI (Maroteaux-Lamy syndrome. In this review, an analysis is made of each of these syndromes, as well as their diagnosis and treatment.

[Mucopolysaccharidosis: clinical features, diagnosis and management]. / Mucopolisacaridosis: características clínicas, diagnóstico y de manejo.

The mucopolysaccharidoses (MPS) are a group of rare (orphan) diseases, characterised by a deficiency of enzymes involved in the metabolism of glycosaminoglycans (GAGs) at lysosomal level. When there is a deficiency of a particular enzyme there is an accumulation of GAGs in the cells resulting in progressive cellular damage, which can affect multiple organ systems and lead to organ failure. Diagnosis is based on knowledge of the clinical manifestations, performing biochemical analyses to identify the type of GAG that is accumulating, and confirm the type of disorder with the corresponding enzymatic determination. Their identification is essential to initiate early treatment, taking into account that multidisciplinary management and enzyme replacement therapy is available for MPS I (Hurler syndrome), MPS II (Hunter syndrome), MPS IV (Morquio syndrome), and MPS VI (Maroteaux-Lamy syndrome. In this review, an analysis is made of each of these syndromes, as well as their diagnosis and treatment.

Síndrome de fibromatosis hialina: reporte de dos casos de una misma familia / Hyaline fibromatosis syndrome: case report of two siblings

El síndrome de fibromatosis hialina es una enfermedad autosómica recesiva rara, que se caracteriza por la presencia de contractura y dolor articular, placas y nódulos hiperpigmentados e hipertrofia gingival, producto de la acumulación de un material amorfo hialino similar al colágeno tipo VI en diferentes tejidos. Esta enfermedad incluye el síndrome de hialinosis sistémica y la fibromatosis hialina juvenil, dos entidades que, durante años, fueron consideradas de manera separada; sin embargo, las características clínicas y la edad de presentación se superponen. Además, ha sido documentado que la causa de ambas entidades se localiza en un mismo gen. Se presentan dos casos de hermanas de una misma familia colombiana afectadas por la enfermedad.

Hyaline fibromatosis syndrome is a rare autosomal recessive disease characterized by the presence of contracture and joint pain, hyperpigmented plaques and nodules and gingival hypertrophy. These findings are the result of the accumulation of a hyaline amorphous material similar to collagen type VI in different tissues. This syndrome includes systemic hyalinosis and juvenile hyaline fibromatosis, two entities that for years were considered separately. However, it has been documented that the cause of both entities is located in the same gene and the clinical features and age of presentation are overlapped. In this study two cases of sisters from a same colombian family affected by the disease are presented.

Síndrome de fibromatosis hialina: reporte de dos casos de una misma familia / Hyaline fibromatosis syndrome: case report of two siblings

El síndrome de fibromatosis hialina es una enfermedad autosómica recesiva rara, que se caracteriza por la presencia de contractura y dolor articular, placas y nódulos hiperpigmentados e hipertrofia gingival, producto de la acumulación de un material amorfo hialino similar al colágeno tipo VI en diferentes tejidos. Esta enfermedad incluye el síndrome de hialinosis sistémica y la fibromatosis hialina juvenil, dos entidades que, durante años, fueron consideradas de manera separada; sin embargo, las características clínicas y la edad de presentación se superponen. Además, ha sido documentado que la causa de ambas entidades se localiza en un mismo gen. Se presentan dos casos de hermanas de una misma familia colombiana afectadas por la enfermedad.(AU)

Hyaline fibromatosis syndrome is a rare autosomal recessive disease characterized by the presence of contracture and joint pain, hyperpigmented plaques and nodules and gingival hypertrophy. These findings are the result of the accumulation of a hyaline amorphous material similar to collagen type VI in different tissues. This syndrome includes systemic hyalinosis and juvenile hyaline fibromatosis, two entities that for years were considered separately. However, it has been documented that the cause of both entities is located in the same gene and the clinical features and age of presentation are overlapped. In this study two cases of sisters from a same colombian family affected by the disease are presented.(AU)

[Hyaline fibromatosis syndrome: case report of two siblings]. / Síndrome de fibromatosis hialina: reporte de dos casos de una misma familia.

Hyaline fibromatosis syndrome is a rare autosomal recessive disease characterized by the presence of contracture and joint pain, hyperpigmented plaques and nodules and gingival hypertrophy. These findings are the result of the accumulation of a hyaline amorphous material similar to collagen type VI in different tissues. This syndrome includes systemic hyalinosis and juvenile hyaline fibromatosis, two entities that for years were considered separately. However, it has been documented that the cause of both entities is located in the same gene and the clinical features and age of presentation are overlapped. In this study two cases of sisters from a same colombian family affected by the disease are presented.

Desenlaces materno-fetales de los embarazos atendidos en el Hospital Universitario de Santander, Bucaramanga (Colombia), 2007-2011. Estudio de cohorte / Maternal and foetal outcomes in twin pregnancies seen at Hospital Universitario de Santander, Bucaramanga (Colombia), 2007-2011. A cohort study

Los embarazos gemelares implican mayor riesgo de complicaciones materno-fetales que los embarazos únicos, particularmente en los monocoriales. El objetivo del trabajo fue describir las características clínicas y los desenlaces materno-fetales, por tipo de placenta (monocorial o bicorial), de los embarazos gemelares atendidos en el Hospital Universitario de Santander (HUS), institución de tercer nivel de complejidad localizada en Bucaramanga (Colombia). Materiales y métodos: estudio descriptivo de cohorte, se incluyeron las pacientes que terminaron un embarazo gemelar entre 2007 y 2011 en el HUS, hospital general de referencia de la región centro-oriental del país. Muestreo consecutivo. Se evaluó la edad gestacional en la primera consulta al hospital, los hallazgos clínicos en la evaluación inicial, la terminación del parto y los resultados perinatales. Se hace análisis descriptivo por tipo de corionicidad. Resultados: se incluyeron un total de 248 gestantes con embarazo gemelar en el periodo de estudio. La mediana de la edad gestacional en la primera atención en el hospital en fue de 34 semanas. Al ingreso, 127 (51,2 %) pacientes se diagnosticaron con embarazo monocorial, pero solo en dos terceras partes coincidió el diagnóstico prenatal de corionicidad con el del posparto. Se diagnosticó RCIU con más frecuencia en embarazos monocoriales que en bicoriales (22,3 vs. 7,5 %), y el doppler se encontró alterado con mayor frecuencia en fetos de embarazo monocorial (7,8 vs. 1,1 %). Los neonatos > 24 semanas de edad gestacional de embarazo monocorial pesaron, en promedio, 109 g (IC 95 %: 34-184) menos que los bicoriales. Conclusiones: los resultados de este estudio sugieren un problema de salud pública en este grupo de pacientes, con inicio tardío de control prenatal, de remisión tardía a centros especializados y capacidad insuficiente para definir corionicidad. Se requiere plantear estrategias de atención que incluyan considerar los embarazos gemelares como alto riesgo y garantizar la atención oportuna y adecuada, orientada por una guía de cuidado diferencial para este grupo de gestantes...

Twin pregnancies, especially monochorionic placentations, are associated with a higher rate of maternal and foetal complications when compared to singleton pregnancies. The objective of this work was to describe the clinical characteristics and the maternal and foetal outcomes according to the type of placentation (monochorial or dichorial) of twin pregnancies delivered at Hospital Universitario de Santander (HUS), a level III institution located in Bucaramanga, Colombia. Materials and methods: Descriptive cohort study. The cohort consisted of patients delivered of a twin pregnancy between 2007 and 2011 at the HUS, a general referral hospital for the central-eastern region of the country. The assessment included gestational age at the time of initial presentation to the hospital, clinical findings during the initial assessment, delivery completion, and perinatal results. Descriptive analysis by chorionicity type. Results: A total of 248 women with a twin pregnancy during the study period were included. The mean gestational age on the first visit to the hospital was 34 weeks. On admission, 127 patients (51.2%) were diagnosed with a monochorionic pregnancy, but only in two thirds of the cases was the prenatal chorionicity diagnosis consistent with the post-partum finding. IUGR was diagnosed more frequently in monochorionic than in dichorionic pregnancies (22.3% v. 7.5%) and abnormal Doppler findings were more frequent in monochorionic foetuses (7.8% v. 1.1%). Neonates > 24 of gestational age in monochorionic pregnancies weigh in average 109 gr (IC 95%: 34-184) less than dichorionic twins. Conclusions: The results of this study suggest a public health problem in this group of patients who come late for their prenatal visits and are late referrals to specialized centres, when there is already a limited ability to determine chorionicity. There is a need to develop care strategies in which twin pregnancies are included as a high-risk condition, and to ensure timely and adequate care provision in accordance with differential care guidelines for this group of pregnant women...

Síndrome de deleción 7Q terminal / 7q35 terminal deletion syndrome

El síndrome de deleción terminal 7q se presenta por una pérdida de un fragmento distal del brazo largo del cromosoma 7, siendo variable dependiendo del tamaño de la región comprometida. Su espectro clínico es amplio con alteración en varios sistemas. Reporte del caso: Paciente de 8 años quien presenta retardo del desarrollo psicomotor, lenguaje verbal ausente, pabellones auriculares en copa, sobreplegamiento del hélix, retrognatia, incisivos prominentes, hiperplasia gingival, mal oclusión dental, hernia umbilical y pie equinovaro. El cariotipo bandeo G (25 metafases analizadas, 550-600 bandas) reporta: 46, XX, del (7) (q35); 46, XX, del (7) (pter → q35:). Las alteraciones fenotípicas varían según el punto de corte cromosómico. Se comparan los hallazgos de la paciente con lo descrito en la literatura. Se establece la importancia de la caracterización clínica y realizar estudio citogenético y molecular para poder tener un diagnóstico oportuno y con esto indicar manejo preventivo y asesoría genética.

7q terminal deletion syndrome is due to a loss of the distal portion of the long arm of chromosome 7; it is variable and depends on the size of the compromised region. Its clinical spectrum is wide and includes several anatomic systems. Case report: The patient is an eightyear- old girl who shows neurodevelopmental delay, absence of speech, cupped ears with overfolding helix, retrognathia, prominent incisors with gingival hyperplasia, dental malocclusion, umbilical hernia and clubfoot. The G-banding karyotype (25 metafases analyzed, 550-600 bands) reported: 46, XX, del (7) (q35), 46, XX, del (7) (pter → q35:). Phenotypic alterations differ due to chromosomal breakpoints. We compare clinical findings of the patient with case reports published in the worldwide literature. It is important to establish a clinical characterization and to perform molecular and cytogenetic studies in order to have a well-timed diagnosis and prescribe preventive management and genetic counseling.

Aborto Recurrente de Etiología Autoinmune / Autoimmune Recurrent Abortion

El curso normal del embarazo implica una serie de cambios inmunológicos que permiten el desarrollo armónico fetal. En mujeres con pérdida recurrente de la gestación, diversas etiologías se han relacionado como desencadenantes de dichas pérdidas; jugando el factor autoinmune un papel cada vez más importante. En el presente artículo, a partir de una búsqueda sistemática de información, se exponen en detalle los aspectos inmunológicos del embarazo normal, así como las alteraciones que a este nivel se presentan en mujeres con aborto recurrente. Además, se realiza una orientación diagnóstica y se exponen las diversas opciones terapéuticas utilizadas, haciendo énfasis en la necesidad de establecer protocolos estandarizados para el manejo de esta entidad.

Normal development of the pregnancy involves a number of immunological changes that allow harmonic fetal development. In women with recurrent pregnancy loss several etiologies have been implicated as triggers of such losses; autoimmune factor is nowadays playing an increasingly more important roll. In this article, based on a systematic search of information, are exposed in details the immunological aspects of normal pregnancy, as well as the immune alterations that occur in women with recurrent abortion. In addition, a diagnostic guidance is made and the various therapeutic options used are pointed out, emphasizing the need to establish standardized protocols for the management of this entity.