Case report: Functional characterization of a de novo c.145G>A p.Val49Met pathogenic variant in a case of PIGA-CDG with megacolon.

A subgroup of congenital disorders of glycosylation (CDGs) includes inherited GPI-anchor deficiencies (IGDs) that affect the biosynthesis of glycosylphosphatidylinositol (GPI) anchors, including the first reaction catalyzed by the X-linked PIGA. Here, we show the first PIGA-CDG case reported in Mexico in a male child with a moderate-to-severe phenotype characterized by neurological and gastrointestinal symptoms, including megacolon. Exome sequencing identified the hemizygous variant PIGA c.145G>A (p.Val49Met), confirmed by Sanger sequencing and characterized as de novo. The pathogenicity of this variant was characterized by flow cytometry and complementation assays in PIGA knockout (KO) cells.

Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice.

Importance: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. Objective: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. Design, Setting, and Participants: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. Exposures: Genetic test results. Main Outcomes and Measures: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. Results: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). Conclusions and Relevance: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes.

Tracheal growth assessment in mongrel puppies (dogs) through multidetector CT.

The aim of this study was to describe the tracheal growth pattern and its zoometric relationship in related medium-sized mongrel puppies through adulthood. Fourteen puppies were studied. CT monitoring was performed monthly, starting in the 1st month of life through the 7th month and subsequently at the 9th and 12th months. Additionally, six zoometric measurements were performed. Dorsoventral (DV) and transverse (TV) diameters and the luminal area from C1 to T2 were obtained. The global tracheal growth pattern revealed an increase up to 13 times its initial size, reaching a plateau phase during the last trimester. The relationship between the DV and the TV internal diameters of the tracheal lumen did not change during growth. As previously reported, the cranial tracheal area was wider, while the caudal part gradually decreased towards T1-T2; this consideration is important since the more distal an endotracheal tube is inserted, the greater the risk that injury may occur. The linear correlation between the zoometric measurements and the tracheal ring areas was positive. This study provides evidence for the evaluation of the morphometry of the canine trachea during physiological growth using helicoidal CT as a non-invasive, accurate tool.

[GASTROSTOMY POSITIVELY AFFECTS NUTRITIONAL STATUS AND DIMINISHES HOSPITAL DAYS IN PATIENTS WITH INBORN ERRORS OF METABOLISM]. / LA GASTROSTOMÍA AFECTA POSITIVAMENTE AL ESTADO NUTRICIONAL Y DISMINUYE LOS DÍAS DE HOSPITALIZACIÓN EN PACIENTES CON ERRORES INNATOS DEL METABOLISMO.

INTRODUCTION: the nutrition management of patients with inborn errors of metabolism (IEM) requires the permanent use of elemental medical formulas whose organoleptic characteristics sometimes impede oral acceptance. In addition, these patients may have gastrointestinal disorders and require constant use of drugs, that often complicate treatment adherence, thereby committing their nutritional status and disease control. Gastrostomy is an alternative to facilitate feeding and treatment, but its use is controversial. OBJECTIVE: to compare nutrition status and length of hospitalizations before and after gastrostomy surgery in a group of IEM patients. METHODS: retrospective analysis of anthropometric data, number of hospitalizations due to metabolic decompensation and length in pediatric patients with IEM before and after gastrostomy. RESULTS: 16 children were analyzed, 40% with propionate disorders, 25% with abnormal urea cycle and 35% other IEM. After gastrostomy, the number of eutrophic patients increased from 6-56%, and malnutrition decreased from 94 to 44%. After gastrostomy inpatient hospital days significantly decrease from 425 to 131 (p = 0.011), admission numbers pre-gastrostomy decreased from 33 to 17, however this difference was not statistically significant. CONCLUSION: in this sample, gastrostomy improved nutritional status in 56% of EIM patients and significantly reduced hospital days caused by metabolic decompensation.

Introducción: el tratamiento nutricional de los pacientes con errores innatos del metabolismo (EIM) implica el uso permanente de fórmulas modificadas en aminoácidos cuyas características organolépticas pueden dificultar su aceptación por vía oral. Estos pacientes pueden tener alteraciones gastrointestinales y requieren el uso constante de medicamentos, lo cual complica la adherencia al tratamiento, comprometiéndose con ello su estado nutricional y el control de la enfermedad. La gastrostomía es una alternativa para facilitar la alimentación y el tratamiento, pero existen controversias sobre su uso. Objetivo: comparar el estado nutricional y la duración de las hospitalizaciones antes y después de la realización de la gastrostomía en un grupo de pacientes con EIM. Métodos: análisis retrospectivo de datos antropométricos, número de internamientos por descompensación metabólica y su duración en pacientes pediátricos con EIM antes y después de la gastrostomía. Resultados: se analizaron 16 niños; 40% con defectos del propionato, 25% con alteraciones del ciclo de la urea y 35% con otros EIM. Después de la gastrostomía, la proporción de pacientes eutróficos aumentó del 6 al 56% y la desnutrición disminuyó del 94 al 44%. Después de la gastrostomía, la duración de los periodos hospitalarios disminuyó significativamente de 425 a 131 días (p = 0.011); el número de internamientos disminuyó de 33 antes de la intervención a 17, sin embargo, esta diferencia no tuvo significación estadística. Conclusión: en esta muestra, la gastrostomía mejoró el estado nutricional en 56% de los pacientes con EIM, y redujo significativamente los días de hospitalización por descompensación metabólica.

La gastrostomía afecta positivamente al estado nutricional y disminuye los días de hospitalización en pacientes con errores innatos del metabolismo / Gastrostomy positively affects nutritional status and diminishes hospital days in patients with inborn errors of metabolism

Introducción: el tratamiento nutricional de los pacientes con errores innatos del metabolismo (EIM) implica el uso permanente de fórmulas modificadas en aminoácidos cuyas características organolépticas pueden dificultar su aceptación por vía oral. Estos pacientes pueden tener alteraciones gastrointestinales y requieren el uso constante de medicamentos, lo cual complica la adherencia al tratamiento, comprometiéndose con ello su estado nutricional y el control de la enfermedad. La gastrostomía es una alternativa para facilitar la alimentación y el tratamiento, pero existen controversias sobre su uso. Objetivo: comparar el estado nutricional y la duración de las hospitalizaciones antes y después de la realización de la gastrostomía en un grupo de pacientes con EIM. Métodos: análisis retrospectivo de datos antropométricos, número de internamientos por descompensación metabólica y su duración en pacientes pediátricos con EIM antes y después de la gastrostomía. Resultados: se analizaron 16 niños; 40% con defectos del propionato, 25% con alteraciones del ciclo de la urea y 35% con otros EIM. Después de la gastrostomía, la proporción de pacientes eutróficos aumentó del 6 al 56% y la desnutrición disminuyó del 94 al 44%. Después de la gastrostomía, la duración de los periodos hospitalarios disminuyó significativamente de 425 a 131 días (p=0.011); el número de internamientos disminuyó de 33 antes de la intervención a 17, sin embargo, esta diferencia no tuvo significación estadística. Conclusión: en esta muestra, la gastrostomía mejoró el estado nutricional en 56% de los pacientes con EIM, y redujo significativamente los días de hospitalización por descompensación metabólica (AU)

Introduction: the nutrition management of patients with inborn errors of metabolism (IEM) requires the permanent use of elemental medical formulas whose organoleptic characteristics sometimes impede oral acceptance. In addition, these patients may have gastrointestinal disorders and require constant use of drugs, that often complicate treatment adherence, thereby committing their nutritional status and disease control. Gastrostomy is an alternative to facilitate feeding and treatment, but its use is controversial. Objective: to compare nutrition status and length of hospitalizations before and after gastrostomy surgery in a group of IEM patients. Methods: retrospective analysis of anthropometric data, number of hospitalizations due to metabolic decompensation and length in pediatric patients with IEM before and after gastrostomy. Results: 16 children were analyzed, 40% with propionate disorders, 25% with abnormal urea cycle and 35% other IEM. After gastrostomy, the number of eutrophic patients increased from 6-56%, and malnutrition decreased from 94 to 44%. After gastrostomy inpatient hospital days significantly decrease from 425 to 131 (p=0.011), admission numbers pre-gastrostomy decreased from 33 to 17, however this difference was not statistically significant. Conclusion: in this sample, gastrostomy improved nutritional status in 56% of EIM patients and significantly reduced hospital days caused by metabolic decompensation (AU)

Tyrosinemia type I: clinical and biochemical analysis of patients in Mexico.

INTRODUCTION: Hepatorenal tyrosinemia (HT1) is a treatable, inherited, metabolic disease characterized by progressive liver failure with pronounced coagulopathy. The aim of this study is to describe the clinical, biochemical, and histopathological findings in a group of Mexican HT1 patients and their outcome. MATERIAL AND METHODS: Medical records of HT1 patients diagnosed between 1995 and 2011 were analyzed. The diagnosis of HT1 was confirmed by detection of succinylacetone in urine or blood. RESULTS: Sixteen nonrelated HT1 cases were analyzed. Mean age at clinical onset was 9 months, and the mean age at diagnosis was 16.3 months. Main clinical findings were hepatomegaly, splenomegaly, cirrhosis, liver failure, tubulopathy, nephromegaly, Fanconi syndrome, seizures and failure to thrive. Histopathological findings were cirrhosis, fibrosis and steatosis. The HT1 group had a mortality rate of 78%. Patients who received supportive care or nutritional treatment had a 3-year survival rate of 10%. For those who underwent liver transplantation, the 6-year survival rate was 60%. In most cases pharmacological treatment with nitisinone and special dietary products were not available. The leading causes of death were fulminant liver failure, metastatic hepatocellular carcinoma, and porphyria-like neurologic crisis. Newborn screening programs in combination with the availability of orphan drugs, proper monitoring, genetic counseling, and clinical practice guidelines are needed to enable physicians to identify the disease, delay its progression, and improve patients' quality of life. CONCLUSION: The devastating natural history of HT1 is still observed in Mexican patients because they are not diagnosed and treated during the early stages of the disease.

Higher incidence of thyroid agenesis in Mexican newborns with congenital hypothyroidism associated with birth defects.

BACKGROUND: Congenital hypothyroidism (CH) is the most common endocrine system disorder in newborns. Ectopic thyroid and agenesis are the most frequent thyroid structural malformations. Several reports have shown that CH is associated with birth defects (BD) ranging from congenital heart disease to ocular and gastrointestinal anomalies. AIMS: We investigated how many and what types of BD were associated with CH in Mexican children. STUDY DESIGN: Cross-sectional study conducted in patients with confirmed CH. SETTING: Highly specialized government pediatric center in Mexico City. SUBJECTS: We included 212 patients with permanent CH identified by newborn screening. RESULTS: We found that 24% of patients with CH also had BD, and that there was a higher prevalence of thyroid agenesis in the group of patients with CH associated with BD (CH+BD) versus the isolated CH group (p=0.007). There were more females than males in both groups. The most common BD were congenital heart diseases, especially those of the atrial septum, followed by patent ductus arteriosus, found as a single malformation or as part of a complex congenital heart disease. In this study, we found Hirschsprung disease, Beckwith-Wiedemann syndrome, Pierre Robin sequence, Albright's osteodystrophy, VATER association, and frontonasal dysplasia associated with CH. CONCLUSIONS: In this study population, there was a high prevalence of BD in patients with permanent CH. Thyroid agenesis was the main etiological cause of CH in patients with associated congenital malformations. The high prevalence of CH+BD underlines the need for a comprehensive clinical diagnostic approach of the patients with CH.

Necrólisis tóxica epidérmica / Toxic epidermal necrolysis

Objetivo: Presentar el caso de una paciente con necrólisis tóxica epidérmica producido por fenitoína sódica y hacer una profunda revisión de la literatura para señalar la importancia del diagnóstico y tratamiento tempranos. Sede: The American British Cowdray Medical Center, IAP, México, D.F. La necrólisis tóxica epidérmica o síndrome de Lyell es una enfermedad idiosincrásica que se presenta como una reacción mucocutánea severa, aguda y episódica producida por fármacos y que compromete la vida. Presentación del caso: se trata de una mujer de 41 años de edad, quien 10 semanas previas a su ingreso presentó enfermedad vascular cerebral isquémica en la cual se administró fenitoína sódica. Inició con malestar general, fiebre, posteriormente presentó edema facial, erupción cutánea generalizada que cubría en 90 por ciento de la superficie corporal total, que rápidamente progresó a bulas hemorrágicas friables, con denudación de la epidermis, acompañándose de involucro de mucosas oral, conjuntival y urogenital. Se brindó tratamiento con aislamiento inverso, lavado de las lesiones y tratamiento con nitrato de plata al 0.5 por ciento, antibioticoterapia de amplio espectro y fisioterapia. Egresó tres semanas después con la vía oral reinstalada, sin secuelas y con reepitelización del 90 por ciento de las lesiones. Conclusión: La necrólisis tóxica epidérmica es una enfermedad bulosa adquirida que puede confundirse con muchas otras. Es indispensable realizar un diagnóstico oportuno para brindar tratamiento multidisciplinario, evitando complicaciones, secuelas o la muerte misma.