Baseline Characteristics of Fabry Disease "Amenable" Migalastat Patients in Argentinian Cohort.

Fabry disease (FD) is a multisystem lysosomal storage disorder induced by genetic variants in the alpha-galactosidase A (αGalA) gene. Some FD patients have GLA variants with a reduction in overall αGalA enzymatic activity due to mutated proteins with reduced stability, caused by protein misfolding and premature degradation, but the αGalA catalytic activity remains conserved ("amenable" genetic variants). To correct this misfolding and to prevent premature degradation, migalastat, a small iminosugar molecule was developed. We report the clinical characteristics of FD "amenable" cohort patients from Argentina, prior to starting treatment with migalastat. Seventeen Fabry adult patients were recruited from 13 Argentinian Centers; 8 males (47.1%) and 9 females (52.9%) were included. All genotypes included were missense-type "amenables" mutations. Some classic FD typical early manifestations were more frequent in patients with "classic" versus "late-onset" FD phenotype (pain, p=0.002; cornea verticillata, p=0.019). There was a statistically significant difference in estimated glomerular filtration rate in the "classic" versus "late-onset" phenotype (p=0.026) but no difference between genders (p=0.695). Left ventricular mass was similar between genders (p=0.145) and phenotypes (p=0.303). Cardiovascular risk factors were present among "late-onset" females (obesity 50% and smoke 25%). In patients who started "de novo" migalastat, the main indications were (i) heart disease, (ii) kidney damage, and (iii) pain, while in "switched from prior enzyme replacement therapy" patients, the most frequent indication was "patient decision;" this coincides with publications by other authors.

New mutation in Fabry disease: c.448delG, first phenotypic description.

Fabry disease (FD) (Anderson-Fabry disease, OMIM 301500) is a genetic disorder caused by a pathogenic variant in the GLA gene on chromosome Xq22 that produces a deficiency in the lysosomal enzyme alpha-galactosidase A. It is transmitted as an X-linked trait, although de novo mutations have been described. The objective of this report is to describe the clinical characteristics of a patient with FD who is a carrier of a mutation not previously studied, in order to provide information on the genotype-phenotype correlation in this pathology. 38-year-old patient who consulted Neurology for positional vertigo. He also reported acroparesthesia, anhidrosis, heat intolerance and episodes of abdominal pain, with postprandial discomfort from 10 years of age. Physical examination showed horizonto-rotatory nystagmus in both looks, the rest of the neurological evaluation did not present abnormalities. The presence of umbilical and thighs angiokeratomas was identified. Determination of Alpha-Galactosidase in blood was requested: 0.34 µmol/l/h (2.10-10.51 µmol/l/h). Genetic analysis detected a deletion of a guanine at position 448, in exon 3 of the GLA gene (c.448delG). This mutation was considered to be pathogenic, confirming the diagnosis of FD, although it is not described in the data bases. Genetic counseling and a family pedifree study were performed without finding relatives with this variant of the GLA gene or a family history of FD, which suggests a de novo mutation.

Enfermedad de motoneurona inferior asociada al signo ojos de serpiente: una nueva entidad clínico-radiológica / Lower motor neuron disease with snake eyes sign: a new clinical-radiological entity

Las enfermedades de la moto neurona inferior constituyen un grupo heterogéneo de entidades con pronósticos diferentes. El signo radiológico "ojos de serpiente" hace referencia a la hiperintensidad bilateral en el asta anterior de la médula espinal en los cortes axiales de las imágenes por resonancia magnética, generalmente asociada a afecciones como infartos espinales, amiotrofia espondilótica, enfermedad de Hirayama y esclerosis lateral amiotrófica. Se ha descripto recientemente un reducido número de casos de enfermedad de moto neurona inferior asociada a "ojos de serpiente" con características clínicas y pronóstico distintivos. Presentamos dos casos de enfermedad de moto neurona inferior asociada al signo "ojos de serpiente" en pacientes jóvenes. El curso clínico fue progresivo con períodos prolongados de estabilidad clínica y ausencia de compromiso de moto neurona superior durante la evolución. Los pacientes presentaron debilidad segmentaria y asimétrica de miembros superiores con predominio distal en el primer caso y proximal en el segundo. Los casos presentados se corresponden en gran parte con lo comunicado en la literatura, dando apoyo a la existencia de una nueva entidad con pronóstico relativamente benigno denominada enfermedad de moto neurona inferior esporádica con signo de ojos de serpiente en las imágenes por resonancia magnética y cuya identificación debiera obviar tratamientos innecesarios (AU)

Lower motor neuron diseases are a heterogeneous group of entities with different prognosis. The "snake eyes" sign refers to bilateral hyper intensity of the anterior horns on axial magnetic resonance imaging of the spinal cord. It has been associated with ischemia, cervical spondylosis, Hirayama disease, and amyotrophic lateral sclerosis. Recently, a small number of cases of lower motor neuron disease associated with the "snake eyes" sign have been described as having distinctive clinical manifestations and prognosis. Two young patients with "snake eyes" sign associated with lower motor neuron disease had a progressive initial course followed by a stabilization of symptoms without involvement of upper motor neuron. They presented with asymmetric segmental arm weakness with distal predominance in the first a case and proximal predominance in the second. These cases match with those reported in the literature giving support to lower motor neuron disease with "snake eyes" as a pathological entity with a relatively good prognosis. This diagnosis should avoid unnecessary treatments (AU)

[Argentine consensus on late-onset Pompe's disease]. / Consenso argentino sobre enfermedad de Pompe de inicio tardío.

Pompe's disease (PD) is an infrequent metabolic autosomic recessive disorder produced by the lack or deficiency of the acid alpha-glucosidase lysosomal enzyme in tissues of involved individuals. Delayed-onset PD is considered whenever symptoms onset start after one year of age. We present an update of the recommendations for the management of delayed-onset PD, taking as reference the guidelines from the Argentine Consensus for diagnosis, treatment and follow-up of PD published in 2013. The present consensus gathered several experts in PD in the areas of internal medicine, laboratory diagnosis, neuropathology, pulmonology, nutrition, neurology, metabolic and neuromuscular disorders as well as rehabilitation to perform an update of the literature of delayed-onset PD, with special attention on relevant information published within the last 4 years. The entire working group approved the final version of the consensus. Each participant provided a declaration of conflict of interest. As a result, it is an update of the previous Argentine PD Consensus with focus on the delayed-onset presentation of the disease. Being such infrequent disorder, available data were rather limited and thus, the recommendations represent expert opinions.

Consenso argentino sobre enfermedad de Pompe de inicio tardío / Argentine consensus on late-onset Pompe's disease

La enfermedad de Pompe (EP) es un desorden metabólico autosómico recesivo infrecuente, producido por la ausencia o deficiencia de la enzima lisosomal alfa-glucosidasa ácida en los tejidos de los individuos afectados. Se considera enfermedad de Pompe de inicio tardío (EPIT) en aquellos individuos de más de un año de edad al comienzo de los síntomas. El objetivo del presente consenso es el de actualizar las pautas y recomendaciones para un correcto tratamiento de los pacientes con EPIT, tomando como referencia los lineamientos del Consenso Argentino para el diagnóstico, seguimiento y tratamiento de la enfermedad de Pompe publicado en el año 2013. Se organizó un consenso que reunió profesionales con experiencia en la EP en las áreas de clínica médica, diagnóstico de laboratorio, neuropatología, neumonología, nutrición, neurología, enfermedades metabólicas, enfermedades neuromusculares y rehabilitación. Se realizó una actualización de la bibliografía sobre EPIT, con especial atención en las publicaciones relevantes de los últimos cuatro años. Los términos finales del documento fueron consensuados por todo el grupo de trabajo. Cada participante proporcionó su declaración de conflicto de intereses. El resultado es una actualización del último Consenso Argentino para la EP, con particular enfoque en su forma de comienzo tardío. Tratándose de una afección infrecuente, en la que los datos disponibles son limitados, las presentes recomendaciones deben ser consideradas como opinión de expertos.

Pompe's disease (PD) is an infrequent metabolic autosomic recessive disorder produced by the lack or deficiency of the acid alpha-glucosidase lysosomal enzyme in tissues of involved individuals. Delayed-onset PD is considered whenever symptoms onset start after one year of age. We present an update of the recommendations for the management of delayed-onset PD, taking as reference the guidelines from the Argentine Consensus for diagnosis, treatment and follow-up of PD published in 2013. The present consensus gathered several experts in PD in the areas of internal medicine, laboratory diagnosis, neuropathology, pulmonology, nutrition, neurology, metabolic and neuromuscular disorders as well as rehabilitation to perform an update of the literature of delayed-onset PD, with special attention on relevant information published within the last 4 years. The entire working group approved the final version of the consensus. Each participant provided a declaration of conflict of interest. As a result, it is an update of the previous Argentine PD Consensus with focus on the delayed-onset presentation of the disease. Being such infrequent disorder, available data were rather limited and thus, the recommendations represent expert opinions.