CONSENSO ARGENTINO SOBRE LA TRANSICIÓN DE LOS CUIDADOS PEDIÁTRICOS A LOS CUIDADOS ADULTOS EN PACIENTES CON ENFERMEDADES CONGÉNITAS DEL METABOLISMO / CONSENSUS STATEMENT ON THE TRANSITION FROM PEDIATRIC CARE TO ADULT CARE IN PATIENTS WITH INBORN ERRORS OF METABOLISM IN ARGENTINA

Introducción: Los errores congénitos del metabolismo (ECM) son enfermedades producidas por trastornos genéticos que alteran la función de distintas vías metabólicas. La transición desde el sistema de atención médica pediátrica a la de adultos es un proceso clave en el desarrollo evolutivo de las personas con condiciones crónicas de salud. Los servicios de salud presentan fallas en satisfacer las necesidades de los jóvenes y sus familias. El objetivo fue definir un conjunto de herramientas y recomendaciones, adaptadas al contexto local de Argentina, para orientar al equipo de salud en el acompañamiento del proceso de transición de cuidados. Asimismo, se buscó analizar barreras y facilitadores para su implementación. Métodos: se definieron preguntas clínicas que se respondieron con la mejor evidencia científica disponible. Se elaboraron recomendaciones para jóvenes y adolescentes con diagnóstico de ECM que se encuentren en proceso de transición entre el servicio de atención pediátrico al servicio de adultos. Las recomendaciones elaboradas se consensuaron con expertos en la temática a través de un método Delphi. Resultados: se elaboraron y consensuaron 13 recomendaciones que permitirán guiar el proceso de transición de los cuidados pediátricos al de adultos en personas con ECM. Conclusiones: estas recomendaciones ayudarán al equipo de salud a mejorar la calidad de atención de estos pacientes y garantizar que ellos y sus familias tengan una experiencia adecuada durante todo el proceso de transición

Introduction: Inborn errors of metabolism (IEM) are diseases caused by genetic disorders that alter the function of different metabolic pathways. The transition from the pediatric to adult health care system is a key process in the evolutionary development of patients with chronic health conditions. Health services are failing to meet the needs of young patients and their families. The objective was to define a set of tools and recommendations, adapted to the local context of Argentina, to guide the health team in accompanying the process of transition. Likewise, it sought to analyze barriers and facilitators for its implementation. Methods: clinical questions were defined and answered with the best available scientific evidence. Recommendations were developed for young patients and adolescents diagnosed with IEM who are in the process of transitioning from the pediatric care service to the adult service. The recommendations developed were agreed with experts in the field through a Delphi method. Results: 13 recommendations were developed and agreed upon to guide the transition process from pediatric to adult care in people with IEM. Conclusions: These recommendations will help the health team improve the quality of care for these patients and ensure that they and their families have an adequate experience throughout the transition process

Consenso Argentino sobre Diagnóstico y Tratamiento de la Enfermedad de Niemann-Pick tipo C / Argentinean Consensus on the Diagnosis and Treatment of Niemann-Pick Disease type C

Resumen La enfermedad de Niemann-Pick tipo C (NPC) es un trastorno del metabolismo lisosomal que se debe a la presencia de variantes patogénicas bialélicas en los genes NPC1 o NPC2. El depósito intracelular de lípidos, especialmente colesterol no esterificado, provoca daño oxidativo en diversos tejidos, especialmente neuronas, bazo e hígado. Esto, a su vez, induce la aparición de un conjunto de síntomas neurológicos/psiquiátricos y viscerales, con una amplia variabilidad de edad de apa rición, desde formas prenatales/neonatales hasta otras de aparición en la vida adulta. En los últimos años ha habido avances considerables en la comprensión sobre esta enfermedad y su manejo. En el presente consenso un grupo de expertos argentinos abordan los enfoques actuales de diagnóstico, seguimiento y tratamiento de NPC, incluyendo el uso de miglustat como única terapia específica aprobada en la actualidad.

Abstract Niemann-Pick type C (NPC) is a disorder of the lyso somal metabolism due to biallelic pathogenic variants in NPC1 or NPC2. Intracellular deposit of lipids, mainly unesterified cholesterol, gives rise to oxidative damage in several tissues, mainly neurons, spleen and liver. This, in turn, is associated with a myriad of neurologi cal/psychiatric and visceral symptoms, with wide vari ability in age of presentation, from prenatal/neonatal to adult-onset forms of the disease. The last few years have seen considerable progress in understanding this disease and its management. In this consensus, current approaches to the diagnosis, follow-up and treatment of NPC (including the use of miglustat, the only specific drug approved at the time) are discussed by an Argentin ian panel of experts.

Algunos desafíos en mucopolisacaridosis tipo I / A few challenges in mucopolysaccharidosis type I

Se describen como desafíos actuales en mucopolisacaridosis I la necesidad de una clasificación adecuada, vinculándola a las indicaciones terapéuticas; el diagnóstico temprano desde la pesquisa neonatal, sus ventajas y dificultades hasta la sospecha clínica de las formas grave y atenuada; el cuidado de la patología espinal y oftalmológica, desde el diagnóstico, el seguimiento y el tratamiento; las reacciones alérgicas por terapia de reemplazo enzimático, su diagnóstico y tratamiento. Por último, la transición hacia el cuidado adulto

Here we describe the current challenges of mucopolysaccharidosis type I: the need for an adequate classification, establishing its relationship to therapeutic indications; an early diagnosis, from neonatal screening, its advantages and barriers, to clinical suspicion of severe and attenuated forms; spinal and eye disease care, from diagnosis to follow-up and treatment; allergic reactions caused by enzyme replacement therapy, their diagnosis and treatment. And lastly, transition to adult care

Nuevas recomendaciones para el cuidado de los pacientes con mucopolisacaridosis tipo I / New recommendations for the care of patients with mucopolysaccharidosis type I

Dados los avances sobre mucopolisacaridosis Icon posterioridad al consenso publicado en la Argentina por un grupo de expertos en 2008, se revisan recomendaciones respecto a estudios genéticos, seguimiento cardiológico, cuidado de la vía aérea, alertas sobre aspectos auditivos, de la patología espinal y neurológica. Se hace revisión de la terapéutica actual y se enfatiza en la necesidad de un diagnóstico y tratamiento precoces, así como de un seguimiento interdisciplinario

Considering the advances made on mucopolysaccharidosis type I after the consensus study published by a group of experts in Argentina in 2008, recommendations about genetic testing, cardiological follow-up, airway care, hearing impairment detection, spinal and neurological conditions, as well as current treatments, were reviewed. Emphasis was placed on the need for early diagnosis and treatment, as well as an interdisciplinary follow-up

Position of Experts Regarding Follow-Up of Patients with Neuronal Ceroid Lipofuscinosis-2 Disease in Latin America

Abstract Given the lack of standardized guidance for follow-up of patients with neuronal ceroid lipofucsinosis-2 disease in Latin-American countries and the heterogeneity of the region, an expert panel was created with the participation of 11 pediatric neurologists from Colombia, Argentina, Brazil and Chile. The aim of the expert panel was to describe a framework for standardized follow-up in patients with neuronal ceroid lipofucsinosis-2 disease, on or off therapy, that could benefit patients and treating physicians alike. Experts made recommendations in the following areas: seizures, abnormal movements and ataxia, sleep disorders and pain, cognitive function, visual function, hearing and speech, cardiac function, quality of life, and motor function. Recommendations include the most appropriate tools for use in the Latin-American context and health care systems, and provide feasible follow-up guidance, applicable in public and private healthcare facilities. They take into consideration the availability of clinical assessment resources, tools (scales, questionnaires, paraclinical tests) and access to these tools in Latin-American countries, as well as other regional and local needs defined by the participating experts.

Enfermedad de Pompe infantil: Diagnóstico y tratamiento / Infantile-onset Pompe disease: Diagnosis and management

La enfermedad de Pompe, o deficiencia de maltasa ácida o glucogenosis tipo II, es una grave enfermedad genética, autosómica recesiva, progresiva, poco frecuente, causada por la deficiencia en la enzima alfa glucosidasa. En la edad pediátrica, puede presentarse con la "forma clásica", la más conocida, con grave compromiso cardíaco y franca hipotonía, o con la "forma no clásica", con comienzo temprano del compromiso motor. La "forma de comienzo tardío" del adulto también puede ocurrir en la infancia o en la adolescencia. Se actualizan los hallazgos clínicos y de diagnóstico disponibles, ya que un tratamiento temprano con reemplazo de la enzima faltante puede mejorar la supervivencia y la calidad de vida del paciente. Se revisan los beneficios y los efectos adversos del tratamiento disponible y nuevas líneas de investigación terapéutica.

Pompe disease, also known as acid maltase deficiency or glycogenosis type II, is a rare severe, autosomal, recessive, and progressive genetic disorder caused by deficiency in alpha-glucosidase. The classic infantile-onset is the most broadly known form of Pompe disease, which presents with severe heart involvement and clear hypotonia, while the non-classic presentation occurs with early motor involvement. Late-onset Pompe disease develops in adults, but it may also occur during childhood or adolescence. Here we update the available clinical and diagnostic findings because an early management with enzyme replacement therapy may improve patients' survival and quality of life. We also review the benefits and adverse effects of available treatments and new lines of therapeutic research.

Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients

Abstract Phenylketonuria (PKU, OMIM 261600) is predominantly caused by mutations in the PAH gene. One hundred and three Argentine PKU patients were studied by Sanger sequencing; 101 were completely characterized (90.3% were compound heterozygotes). Fifty-four different pathogenic variants were identified. Mutations were distributed all along the PAH gene but concentrated in exon 7 (26%), 12 (12%), 11 (10%), and 6 (10%). 77% were missense, and 77% affected the enzyme catalytic domain, nine mutations accounted for 57% of 179 studied alleles: p.Arg261Gln (Allele frequency(AF):10.6%), c.1066-11G>A (AF:9,5%), p.Arg408Trp (AF:8,3%), p.Tyr414Cys (AF:5,5%), p.Ala403Val, p.Val388Met, and p.Arg158Gln (AF: 5% each), p.Leu48Ser, and p.Ile65Thr (AF:4% each). The predicted phenotype was assigned by Guldberg´s arbitrary value (AV) and compared with the clinical phenotype based in tolerance to Phe intake. 29.1% (n:30) were hyperphenylalaninemias, 18.5% (n:19) mild-PKU, 27.2% (n:28) moderate-PKU and 25.2 % (n:26) classical-PKU. Genotype/phenotype correlation was statistically significant (p<0.001) Overall concordance was 62,5%: 93.3% in hyperphenylalaninemia, 64.7% in mild-PKU and 65.4% in classical patients. The moderate-PKU showed a weak concordance (17%) with milder AV prediction than clinical assessment. 74% of discordant moderate patients harbored p.Arg261Gln, and p.Val388Met. Our cohort is highly heterogeneous, with predominant Mediterranean influence (mainly Spanish), but with differences with other Latin-American countries.

Alternative Therapies for PKU

Abstract The phenylalanine (PHE)-restricted diet has improved in quality and diversity over time and has proven to be effective in all patients. Nevertheless, this treatment imposes a heavy social and economic burden to patient and family and impacts quality of life. Sustained adherence to PHE restriction is difficult to maintain. Moreover, even patients with phenylketonuria (PKU) with normal intelligence quotient (IQ) have lower IQ than matched individuals without PKU and can have deficits in multiple other aspects of neuropsychological function, including cognitive and executive function, working memory. They can also have behavior problems, depression, and low self-esteem. In recent years, alternative treatments for PKU have been developed and their use has been indicated for some patients who are candidates for options besides traditional treatment. Sapropterindihydrochloride, large neutral amino acids, and glycomacropeptide are alternative treatment options in use for selected patients. The aim of this article is to review the current knowledge of these new approaches to PKU treatment.

Enfermedad de Pompe: presentación de un caso / Pompe disease: a case report

Presentamos el caso de una niña de 6 meses de ascendencia china con enfermedad de Pompe diagnosticada a partir de una miocardopatia hipertrófica biventricular e hipotonía global. En esta enfermedad el acumulo de glucógeno lisosomal principalmente en el corazón y músculo esquelético ocasiona la mayoría de la sintomatología clínica. En este paciente la hipotonía generalizada, macroglosia, debilidad en el llanto y la confirmación ecocardiográfica de una miocardiopatía hipertrófica biventricular fueron el punto inicial para la sospecha clínica de la enfermedad que, junto a la elevación de encimas musculares y hepáticas, condujo al estudio de alfa-glucosidasa ácida (AGA) que confirmo el diagnóstico. Desde el 2006 existe terapia de reemplazo enzimático que permite mejorar la sobrevida y la calidad de vida si el diagnóstico se realiza precozmente.

Resúmen de los datos clínicos / Abstarcts of clinics informes

Niño de 4 meses, desnutrido (Grado 1), que ingresó por síndrome de dificultad respiratoria progresiva de 5 días de evolución. Recibio un tratamiento con nebulizaciones de solución fisiológica y salbutamol. No se registro medicación con AAS

Hiperinsulinismo congenito de inicio neonatal / Congenital hyperinsulinemia of neonatal onset

Se presenta el caso de un (RN) derivado por hipoglucemia persistente y necesidad de aporte endovenoso de glucosa con flujo superiores a 15-20 mg/kg/minuto. Se expone un algorritmo racional de uso de laboratorio para establecer el diagnostico y el tratamiento