RESUMEN
We here present the case of a patient with a congenital myasthenic syndrome (CMS) due to pathogenic variants in the RAPSN gene. During childhood he experienced recurrent episodes of respiratory failure during respiratory infections. This and other cases were reported as isolated dystrophy of the diaphragmatic musculature. In adulthood, whole exome sequencing revealed two heterozygous pathogenic variants in the RAPSN gene. This led to the revision of the diagnosis to rapsyn CMS11 (OMIM:616326, MONDO:0014588). EMG, muscle ultrasound and the revision of muscle biopsies taken in childhood support this diagnosis. After the revision of the diagnosis, treatment with pyridostigmine was started. This resulted in a reduction of fatigability and an improvement in functional abilities and quality of life.
Asunto(s)
Distrofias Musculares , Síndromes Miasténicos Congénitos , Masculino , Humanos , Síndromes Miasténicos Congénitos/genética , Diafragma , Calidad de Vida , MutaciónRESUMEN
Cerebellar ataxia can have many genetic causes among which are the congenital disorders of glycosylation type I (CDG-I). In this group of disorders, a multisystem phenotype is generally observed including the involvement of many organs, the endocrine, hematologic and central nervous systems. A few cases of CDG-Ia have been reported with a milder presentation, namely cerebellar hypoplasia as an isolated abnormality. To identify patients with a glycosylation disorder, isofocusing of plasma transferrin is routinely performed. Here, we describe two CDG-Ia patients,who presented with mainly ataxia and cerebellar hypoplasia and with a normal or only slightly abnormal transferrin isofocusing result. Surprisingly, the activity of the corresponding enzyme phosphomannomutase was clearly deficient in both leucocytes and fibroblasts. Therefore, in patients presenting with apparently recessive inherited ataxia caused by cerebellar hypoplasia and an unknown genetic aetiology after proper diagnostic work-up, we recommend the measurement of phosphomannomutase activity when transferrin isofocusing is normal or inconclusive.