| Research Abstract |
Patients with mitochondrial fatty acid β-oxidation disorders (FAODs) have often acute encephalopathy-or sudden infant death-like illness, although such patients in the stable condition do not any clinical symptoms. Recently, newborn mass screening for FAODs as well as organic and amino acid disorders using ESI/MS/MS has attracted attention worldwide. Hence, we studied on the incidence and natural clinical course of Japanese patients with FAODs, and enzymatic and molecular diagnosis. The results were as follows :
1) Survey of Japanese patients with FAODs : We investigated Japanese 71 patients with FAODs during the period between 1985 and 2001. CPT2 deficiency was most common, followed by VLCAD deficiency and glutaric academia type 2 (GA2). Age at onset, and prognosis of FAODs were investigated, being compared with that of organic acidemias (OAs). The age at onset of FAODs tended to be later than OAs, and the incidence of neurological impairments was smaller than that of OAs, in particula
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r in later onset cases.
2) Molecular studies of VLCAD deficiency : We have found 21 Japanese VLCAD deficiency patients. Of the 21 patients, 18 cases were the myopathic form, in contrast with that in the western countries VLCAD deficient patients with the severer forms were more common. There were several common mutations in the VLCAD gene from Japanese patients.
3) Molecular studies of GA2 : We first found two patients with GA2 due to α-subunit of ETF protein, and characterized the pathophisiology at the molecular levels. We also newly identified 3 patients with GA2 due to defeciency of β-subunit of ETF.
4) Development of biochemical diagnostic methods using GC/MS : We developed the diagnostic method by serum free fatty acid analysis using GC/MS, This method could be a useful tool to compliment the data from newborn mass screening for FAODs using ESI/MS/MS. Furthermore, we developed a single method by urinary organic acid analysis by GC/MS to precisely detect patients with peroxisomal β-oxidation disorders. Less
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