TY - JOUR
T1 - Females with PDHA1 gene mutations
T2 - A diagnostic challenge
AU - Willemsen, Marjolein
AU - Rodenburg, Richard J.T.
AU - Teszas, Alexandra
AU - van den Heuvel, Lambert
AU - Kosztolanyi, Gyorgy
AU - Morava, Eva
PY - 2006/6
Y1 - 2006/6
N2 - Biochemical analysis was performed in muscle tissue and in fibroblasts of four unrelated females consecutively diagnosed with a 'de novo' point mutation in the PDHA1 gene. Pyruvate dehydrogenase E1 subunit deficiency was confirmed in the muscle sample of all patients, however, in three out of four cases the activity of the pyruvate dehydrogenase complex in fibroblasts showed a normal activity. A skewed inactivation was confirmed of the maternal X chromosome in fibroblasts in all children. Due to the possibility of a skewed X inactivation pattern enzyme measurements in fibroblasts are not always reliable for the diagnosis of a PDHc defect in females. Based on the overlapping features of PDHc deficiency with those of the disorders of the oxidative phosphorylation we suggest performing a fresh muscle biopsy for detailed biochemical analysis in females with a suspected pyruvate dehydrogenase deficiency, followed by molecular genetic analysis of the PDHA1 gene.
AB - Biochemical analysis was performed in muscle tissue and in fibroblasts of four unrelated females consecutively diagnosed with a 'de novo' point mutation in the PDHA1 gene. Pyruvate dehydrogenase E1 subunit deficiency was confirmed in the muscle sample of all patients, however, in three out of four cases the activity of the pyruvate dehydrogenase complex in fibroblasts showed a normal activity. A skewed inactivation was confirmed of the maternal X chromosome in fibroblasts in all children. Due to the possibility of a skewed X inactivation pattern enzyme measurements in fibroblasts are not always reliable for the diagnosis of a PDHc defect in females. Based on the overlapping features of PDHc deficiency with those of the disorders of the oxidative phosphorylation we suggest performing a fresh muscle biopsy for detailed biochemical analysis in females with a suspected pyruvate dehydrogenase deficiency, followed by molecular genetic analysis of the PDHA1 gene.
KW - Females
KW - Fibroblast
KW - Mitochondrial disease score
KW - Muscle biopsy
KW - PDH
KW - Skewed X inactivation
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U2 - 10.1016/j.mito.2006.03.001
DO - 10.1016/j.mito.2006.03.001
M3 - Article
C2 - 16713755
AN - SCOPUS:33745142205
SN - 1567-7249
VL - 6
SP - 155
EP - 159
JO - Mitochondrion
JF - Mitochondrion
IS - 3
ER -