ABSTRACT
Abstract Introduction: Glutaric Aciduria Type 1 (GA-1) is produced by the enzymatic deficiency of glutaryl-CoA-dehydrogenase (GCDH), leading to the accumulation of glutaric acid (GA). 90% of patients without early treatment present acute encephalopathic crisis (AEC), followed by disabling neurological symptoms. The treatment consists of a low lysine (Lys) diet, protein substitute lys-free, tryptophan-reduced (PS) and L-carnitine. Objectives: Describe the clinical and nutritional evolution of a cohort of GA-1 patients at a national referral center in Chile. Methodology: Retrospective study of 24 patients diagnosed with GA-1 between 1998-2020 and referred to the Institute of Nutrition and Food Technology (INTA) of University of Chile. Results: Age at diagnosis was 19±27 months; 10/24 presented AEC and neurological sequelae. The cases without AEC (14/24) 8 presented neurological compromise: psychomotor development delay, abnormal movements and pyramidal syndrome. Nutritional evaluation: 12/24 were malnourished by deficiency, <6 years old group (12/24): 11 cases were found to have Lys and PS, ≥6 years old (12/24): 9/12 did not receive PS. All had normal free carnitine levels. Conclusion: GA-1 has variable symptoms with neurological involvement AEC or insidious start. Is essential to maintain a long-term follow-up and consider its inclusion in neonatal screening programs.
ABSTRACT
Las hiperfenilalaninemias se definen por un nivel sanguíneo de fenilalanina sobre 2 mg/dl. La principal causa es una mutación en el gen que codifica la fenilalanina hidroxilasa que cataliza la reacción que transforma la fenilalanina en tirosina. Las hiperfenilalaninemias se clasifican en benignas o leves, y las fenilcetonurias en leves, moderadas y clásicas. Debido a que su detección más allá del periodo neonatal causa retardo mental severo, desde 1992 en Chile su detección, junto con la del hipotirodismo congénito, es parte del Programa Nacional de Pesquisa Neonatal. Este artículo pretende responder las preguntas más comunes que se puede hacer el pediatra cuando enfrenta a un paciente con hiperfenilalaninemias.
Hyperphenylalaninaemias are defined by a blood phenylalanine over 2 mg/dl. The main cause is due to a mutation in the gene that codes the phenylalanine hydroxylase that catalyses the reaction that converts phenylalanine into tyrosine. The hyperphenylalaninaemias are classified into benign or mild hyperphenylalaninaemias, or mild, moderate or classic phenylketonurias. Due to its delayed detection outside the neonatal period it causes severe mental retardation. Its detection along with congenital hypothyroidism has been part of the National Neonatal Screening Program since 1992 in Chile. This article aims to answer the most common questions asked by the paediatrician when faced with a patient with hyperphenylalaninaemias.
Subject(s)
Humans , Infant, Newborn , Phenylalanine/blood , Phenylketonurias/diagnosis , Neonatal Screening/methods , Pediatrics , Phenylalanine Hydroxylase/genetics , Phenylalanine Hydroxylase/metabolism , Phenylalanine/metabolism , Phenylketonurias/complications , Phenylketonurias/genetics , Tyrosine/metabolism , Chile , Delayed Diagnosis , MutationABSTRACT
La enfermedad de Gaucher, por su escasa frecuencia, está incluida dentro de las llamadas enfermedades huérfanas. En 1991 se creó el Registro Internacional de Gaucher y en 1992 se incorporaron los primeros pacientes de Latinoamérica. En el año 2008 se creó el Grupo Latinoamericano para la Enfermedad de Gaucher (GLAEG) cuyos principales objetivos son fomentar la realización de consensos regionales, difundir el ingreso de pacientes al registro internacional y aumentar el conocimiento sobre la enfermedad para lograr mejorar la atención y la calidad de vida de los pacientes. Hasta abril del 2010 ingresaron 5828 pacientes de todo el mundo, 911 (15.6%) son de Latinoamérica. Este es el primer informe global de la enfermedad en la Región: hay un predominio del sexo femenino, la forma clínica más frecuente es el tipo I (95%); al diagnóstico la mayoría son <20 años (68%). Las manifestaciones clínicas más frecuentes al diagnóstico son esplenomegalia (96%) y anemia (49%), el 80% presentó hallazgos radiológicos de compromiso óseo. En nuestra Región, la gran mayoría de los pacientes (89%) ha recibido alguna vez terapia de reemplazo enzimática con imiglucerasa logrando, con un seguimiento prolongado (hasta10 años), las metas terapéuticas que muestran la gran eficacia de la terapia. Si bien el porcentaje de pacientes con terapia es alto, las suspensiones de tratamiento son frecuentes. Las principales deficiencias en nuestra Región son: la carencia de evaluaciones viscerales volumétricas, de densitometría y de estudios moleculares en algunos pacientes. El principal problema es el subdiagnóstico.
Gaucher disease -due to its low frequency- is considered an orphan disease. In 1991 the International Gaucher Registry was created and in 1992 the first patients from Latin America were enrolled. In 2008 the Latin American Group for Gaucher Disease was initiated. Its main objectives are to promote regional consensus, to stimulate the enrolment of patients into the International Gaucher Registry and the enhancement of knowledge on this disease, and to achieve better care and quality of life of patients in our Region. Until April 2010, 5828 patients have been enrolled all around the world, 911 (15.6%) from Latin America. This is the first comprehensive report of the disease in the Region. In our population there is a predominance of females, the most common clinical form is the type I (95%) and the age at diagnosis is before 20 years in 68% of patients. The most frequent clinical manifestations at diagnosis are splenomegaly (96%) and anemia (49%). Eighty percent of patients had radiographic findings of bone involvement. In our Region, the vast majority of patients (89%) had received enzyme replacement therapy with imiglucerase; with a long follow-up (up to 10 years) they have achieved the therapeutic goals, showing the great effectiveness of therapy. While the percentage of patients with therapy is high, discontinuations are common. The main deficiencies in our Region are: the lack of visceral volumetric evaluations and densitometries as well as molecular analysis for some patients. The main problem is the under-diagnosis of patients.
Subject(s)
Female , Humans , Male , Gaucher Disease/diagnosis , Rare Diseases , Anemia/etiology , Enzyme Replacement Therapy , Gaucher Disease/epidemiology , Gaucher Disease/therapy , Glucosylceramidase/therapeutic use , Latin America/epidemiology , Rare Diseases/diagnosis , Rare Diseases/epidemiology , Rare Diseases/therapy , Sex Distribution , Splenomegaly/etiology , Global Health/statistics & numerical dataABSTRACT
Gracias a los avances tecnológicos, los niños prematuros con discapacidades físicas mayores han disminuido su prevalencia; actualmente, los defectos cognitivos son la secuela predominante. Se investigó el desarrollo cognitivo y la atención en escolares con antecedentes de haber sido recién nacidos prematuros, a través de un estudio descriptivo, de corte transversal, en que se realizaron evaluaciones neuropsicológicas mediante WISC-R y test de Gordon a niños escolares con antecedentes de prematurez (EG<33s y/o PN<1500g) y niños controles con antecedentes de ser recién nacidos de término. Se evaluó a 77 pacientes: 40 niños prematuros (EG: 30,5 s) y 37 de término, entre 6-7 años. Aunque ambos grupos obtuvieron un CIT dentro del rango normal, se observó diferencias significativas (p<0,03) en desmedro del grupo prematuro en comparación con controles. Las habilidades atencionales también fueron significativamente menores para los prematuros (p< 0,01). Los niños prematuros se encuentran en riesgo de presentar problemas cognitivos y/o de atención en la etapa escolar. Se sugiere incorporar instrumentos de pesquisa de estas dificultades durante el seguimiento, que permitan un reconocimiento precoz e intervención oportuna.
The prevalence of premature children with major physical disabilities has diminished over time mainly due to advances in technology. Cognitive disorders are currently the main sequels. In order to study cognitive and attentional functioning of extremely premature infants at school age, a cross sectional study was designed. Neuropsychological assessments were performed by WISC-R and Gordon test, in prematures and controls at school age. Seventy seven children, 40 preterm (GA: 30.5 w) and 37 term at birth, aged 6-7 years-old were assessed. Although both groups obtained an overall IQ within the normal range, prematures showed significantly lower scores than the control group (p< 0.03). Attentional skills were also significantly lower (p <0.01) in the premature children. Children with a history of extreme prematurity are at risk for cognitive and attention impairment at school age. We suggest to introduce screening tools during follow-up which allow early recognition and appropriate intervention.
Subject(s)
Humans , Male , Female , Infant, Newborn , Child , Premature Birth/physiopathology , Attention Deficit Disorder with Hyperactivity/diagnosis , Attention Deficit Disorder with Hyperactivity/physiopathology , Cognition Disorders/diagnosis , Cognition Disorders/physiopathology , Birth Weight , Case-Control Studies , Developmental Disabilities , Infant, Premature, Diseases , Intelligence , Intelligence Tests , Neuropsychological Tests , Reference Values , Attention Deficit Disorder with Hyperactivity/etiology , Cognition Disorders/etiologyABSTRACT
Background: Tyrosinemia type I is an inborn error of metabolism due to deficiency of fumarilacetoacetase. Acute presentation is with liver failure, hypophosphatemic rickets and peripheral neuropathy. Chronic presentation is with visceromegaly and subclinical rickets. The most severe complications are hepatic cancer and acute neurological crises. Without treatment, tyrosinemia type 1 is fatal. In 1992 treatment for tyrosinemia type 1 with 2-(2-nitro-4-trifluoromethybenzoyl)-1,3-ciclohexanedione (NTBC) was proposed. A clinical response was reported in 90% of patients. In cases that did not respond, a successful liver transplantation was performed, reducing mortality to 5%. Aim: To report the follow up of 12 patients treated with NTBC. Patients and Methods: Review of clinical records of 12 Chilean cases treated with NTBC at the Instituto de Nutrición y Tecnología de los Alimentos (INTA) from January 2004 until June 2010. Results: In all patients, a rapid metabolic control was achieved. Two patients developed hepatocarcinoma. One of these patients died and one was successfully treated with liver transplantation. One patient died after receiving a liver transplantation. Nine patients have at present good liver function, but 2 had peripheral neuropathy due to late diagnosis and discontinuing NTBC treatment. Conclusions: Treatment with NTBC allows metabolic normalization in tyrosinemia type 1, prevents liver cirrhosis and hepatic cancer, improving survival rates and quality of life in the patients. Neonatal screening is essential for the early diagnosis of this treatable disease, that otherwise may be lethal.
Subject(s)
Child, Preschool , Female , Humans , Infant , Male , Cyclohexanones/therapeutic use , Enzyme Inhibitors/therapeutic use , Nitrobenzoates/therapeutic use , Tyrosinemias/drug therapy , Chile , Follow-Up Studies , Liver Neoplasms/etiology , Liver Neoplasms/prevention & control , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Retrospective Studies , Time Factors , Treatment Outcome , Tyrosinemias/complications , Tyrosinemias/metabolismABSTRACT
La Fenilquetonuria (PKU) se produce por un defecto total o parcial de la enzima fenilalanina hidroxilasa (FAH) acumulándose fenilalanina (FA) en sangre, lo que ocasiona retardo mental si no es diagnosticada en el período de recién nacido. El tratamiento consiste en una dieta restringida en FA. Diversos estudios han señalado que debido a la restricción de proteínas animales, la dieta es deficiente en ácidos grasos: alfalinolénico (ALL) y elevada en ácidos linoléico (AL). El objetivo de este estudio fue determinar la ingesta de lípidos en niños PKU diagnosticados precozmente, estudiándose la composición química de lípidos de la dieta de 29 niños con PKU, en dieta restringida en FA y en seguimiento en el INTA, Universidad de Chile. Fueron pareados por sexo y edad con un grupo control. Se aplicó encuesta de recordatorio de 24 horas por tres días consecutivos, calculándose la ingesta de ácidos grasos totales, saturados, monoinsaturados, poliinsaturados, AL y ALL. Los resultados muestran que la dieta de los PKU aporta el 31.8 por ciento como calorías grasas, de los cuales el 13 por ciento es AL y un 0.2 por ciento ALL, existiendo diferencias significativas con respecto al grupo control. La relación obtenida entre ácidos grasos saturados-monoinsaturados-poliinsaturados fue de 1:1.7:3.9 y la razón entre AL y ALL fue diez veces más de lo recomendado (115:1). Concluyéndose que la dieta de los niños PKU chilenos contiene mayor cantidad de AL y menor de ALL