Abnormal fatty acid metabolism in childhood spinal muscular atrophy

Our previous experience with abnormal fatty acid metabolism in several chil dren with spinal muscular atrophy (SMA) prompted evaluation of fatty acid m etabolism in a larger cohort. Thirty-three infants with severe infantile SI MA were shown to have a significantly increased ratio of dodecanoic to tetr adecanoic acid in plasma compared with normal infants and 6 infants affecte d with equally debilitating, non-SMA denervating disorders. Seventeen child ren with milder forms of SMA had normal fatty acid profiles. In addition, a ll 5 infants with severe SMA evaluated in a fasting state developed a disti nctive and marked dicarboxylic aciduria, including saturated, unsaturated, and S-hydroxy forms, comparable in severity with the dicarboxylic aciduria of children with primary defects of mitochondrial fatty acid beta-oxidation . Nine children with chronic SMA and 23 control patients did not develop an abnormal dicarboxylic aciduria during fasting. No known disorder of fatty acid metabolism explains all of the abnormalities we find in SMA. Our data suggest, however, that the abnormalities are not a consequence of SMA-relat ed immobility, systemic illness, muscle denervation, or muscle atrophy. The se abnormalities in fatty acid metabolism may be caused by changes in cellu lar physiology related to the molecular defects of the SMA-pathogenic survi val motor neuron gene or neighboring genes.