2-KETOGLUTARATE DEHYDROGENASE-DEFICIENCY, A RARE CAUSE OF PRIMARY HYPERLACTATEMIA - REPORT OF A NEW CASE

被引:32
作者
GUFFON, N
LOPEZMEDIAVILLA, C
DUMOULIN, R
MOUSSON, B
GODINOT, C
CARRIER, H
COLLOMBET, JM
DIVRY, P
MATHIEU, M
GUIBAUD, P
机构
[1] FAC MED ALEXIS CARREL,DEPT RECH NEUROMUSCULAIRES,CNRS,F-69372 LYON 08,FRANCE
[2] HOP DEBROUSSE,CTR ETUD MALAD METAB,F-69322 LYON 05,FRANCE
[3] UNIV LYON 1,CNRS,BIOL & TECHNOL MEMBRANES LAB,F-69622 VILLEURBANNE,FRANCE
关键词
D O I
10.1007/BF00714273
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Two new familial cases of 2-ketoglutarate dehydrogenase (2-KGD) deficiency are reported: a girl who died at 10 years and a boy, still alive at 4 years, born to consanguineous parents. The cases developed progressively severe encephalopathy with axial hypotonia, psychotic behaviour, pyramidal symptoms and failure to thrive. Both children exhibited permanent lactic acidosis with acute episodes during emotional stress and various infections, associated with elevated lactate/pyruvate (L/P) ratio and slightly decreased ketone body ratio in plasma. In fibroblasts, the L/P ratio was greatly increased in the boy. No respiratory chain complex deficiency could be demonstrated in cultured fibroblasts or in mitochondria isolated from a muscle biopsy performed on the boy. In muscle isolated mitochondria, a progressive decrease of the rate of glutamate oxidation was observed after ADP addition; the rate of 2-ketoglutarate oxidation was low in the absence of ADP and did not increase after ADP addition. 2-KGD deficiency was demonstrated in fibroblasts from both children and in the boy's muscle and myoblasts. The 2-KGD complex is composed of three separate enzymes: E1, E2 and E3. We could demonstrate in our patient that the E1 and E3 subunits were normal, suggesting that the E2 component could be responsible for the defect.
引用
收藏
页码:821 / 830
页数:10
相关论文
共 10 条
[1]   ALPHA-KETOGLUTARATE DEHYDROGENASE-DEFICIENCY PRESENTING AS CONGENITAL LACTIC-ACIDOSIS [J].
BONNEFONT, JP ;
CHRETIEN, D ;
RUSTIN, P ;
ROBINSON, B ;
VASSAULT, A ;
AUPETIT, J ;
CHARPENTIER, C ;
RABIER, D ;
SAUDUBRAY, JM ;
MUNNICH, A .
JOURNAL OF PEDIATRICS, 1992, 121 (02) :255-258
[2]   FATAL INFANTILE CYTOCHROME-C OXIDASE DEFICIENCY - DECREASE OF IMMUNOLOGICALLY DETECTABLE ENZYME IN MUSCLE [J].
BRESOLIN, N ;
ZEVIANI, M ;
BONILLA, E ;
MILLER, RH ;
LEECH, RW ;
SHANSKE, S ;
NAKAGAWA, M ;
DIMAURO, S .
NEUROLOGY, 1985, 35 (06) :802-812
[3]  
CHANCE B, 1956, ADV ENZYMOL REL S BI, V17, P65
[4]  
COLLOMBET JM, 1993, PEDIATRIE, V48, P287
[5]   EFFECTS OF CHRONIC TORBAFYLLINE TREATMENT ON ENERGY-METABOLISM OF ISCHEMIC SKELETAL-MUSCLE [J].
COMTE, J ;
GAUTHERON, DC ;
GODINOT, C ;
OKYAYUZBAKLOUTI, I .
DRUG DEVELOPMENT RESEARCH, 1990, 20 (03) :291-299
[6]   HUMAN CULTURED MYOBLASTS - A MODEL FOR THE DIAGNOSIS OF MITOCHONDRIAL DISEASES [J].
DUMOULIN, R ;
MANDON, G ;
COLLOMBET, JM ;
BLOND, JL ;
CARRIER, H ;
GODINOT, C ;
FLOCARD, F ;
VILLARD, J ;
GUIBAUD, P ;
MATHIEU, M ;
MOUSSON, B .
JOURNAL OF INHERITED METABOLIC DISEASE, 1993, 16 (03) :545-547
[7]   A FAMILIAL PROGRESSIVE NEURODEGENERATIVE DISEASE WITH 2-OXOGLUTARIC ACIDURIA [J].
KOHLSCHUTTER, A ;
BEHBEHANI, A ;
LANGENBECK, U ;
ALBANI, M ;
HEIDEMANN, P ;
HOFFMANN, G ;
KLEINEKE, J ;
LEHNERT, W ;
WENDEL, U .
EUROPEAN JOURNAL OF PEDIATRICS, 1982, 138 (01) :32-37
[8]   THE USE OF SKIN FIBROBLAST-CULTURES IN THE DETECTION OF RESPIRATORY-CHAIN DEFECTS IN PATIENTS WITH LACTACIDEMIA [J].
ROBINSON, BH ;
GLERUM, DM ;
CHOW, W ;
PETROVABENEDICT, R ;
LIGHTOWLERS, R ;
CAPALDI, R .
PEDIATRIC RESEARCH, 1990, 28 (05) :549-555
[9]  
Shepherd D., 1969, METHOD ENZYMOL, P11, DOI [10.1016/0076-6879(69)13006-2, DOI 10.1016/0076-6879(69)13006-2]
[10]   MAPLE SYRUP URINE DISEASE - ANALYSIS OF BRANCHED-CHAIN KETOACID DECARBOXYLATION IN CULTURED FIBROBLASTS [J].
WENDEL, U ;
WENTRUP, H ;
RUDIGER, HW .
PEDIATRIC RESEARCH, 1975, 9 (09) :709-717