6533b831fe1ef96bd12982ef

RESEARCH PRODUCT

G.P.192

subject

description

After uneventful pregnancies, two newborn siblings, a girl and a boy – another sibling was stillborn – developed inspiratory stridor, hypertrophy of the right cardiac ventricle, reduction in spontaneous movements and mildly elevated creatine kinase. Muscle biopsies at ages of three months and seven weeks were performed and respectively, revealed a 'prepathological' pattern of infantile neurogenic atrophy suggesting spinal muscular atrophy (SMA). However, molecular analyses of SMN (SMA) and IGHMBP2 (SMARD1) genes did not disclose any mutations. Further histochemical staining of the skeletal muscle and heart demonstrated almost complete absence of cytochrome c oxidase while SDH was preserved. Subsequent sequencing of SCO2 , coding for a protein required for assembly and functioning of cytochrome c oxidase and cause of fatal infantile cardioencephalomyopathy, revealed two pathogenic heterozygous mutations. In addition to muscle biopsy findings, we present the postmortem neuropathological analyses that were performed on the brain and the spinal cord of the newborn boy. There was no overt evidence of a significant loss or degeneration of anterior horn cells arguing for a very mild loss, or a functional defect of motorneurons. Our findings confirm that mutations of the SCO 2 gene should be considered as a possible cause of neurogenic atrophy including SMA-like phenotype.