An inherited defect affecting the tricarboxylic acid cycle in a patient with congenital lactic acidosis

Blass, John P.; Schulman, J D; Young, Donald S.; Hom, E Lizabeth A. T

doi:10.1172/jci106986

Cited by 78 publications

(25 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Direct assay of this enzyme and lipoamide dehydrogenase would be required for this conclusion to be certain, but the assays have proven difficult to adapt to the small amount of material available from cultured fibroblasts. These observations confirm and extend previous studies of cells from another patient with lactic acidosis of childhood (4,9). and are in contrast to most other patients with PDH deficiency in whom the defect appears to be in PDC (3-6, 8, 16, 18, 19).…”

Section: Discussionsupporting

confidence: 90%

“…The close correlation between the total lactate excreted and the bicarbonate deficit suggests that lactate was the major acidic metabolite produced by the tissues of the patient. Similar sensitivity to carbohydrates (or dependence on fats) has been demonrtrated in three other patients with P D C deficiency (16,17,19); another patient with P D H deficiency reportedly did better on a high fat diet, but control studies could not be done (9).…”

Section: Discussionsupporting

confidence: 54%

“…Fibroblasts, grown and harvested as described previously (3,9), were studied between 10 and 25 passages for all experiments, although we have found no changes in activities in up to 35 passages. Both control and patient cells had a doubling time of 3 days and were morphologically indistinguishable.…”

mentioning

confidence: 88%

“…More recently, in several of these patients (SGOT, SGPT), lactate dehydrogenase (LDH), creatine phosinherited abnormalities affecting specific enzymes of carbohydrate phokinase, aldolase, alkaline phosphatase, total serum protein and metabolism have been demonstrated. These include deficiencies of electrophoresis, quantitative immunoglobulins, VDRL, T,, cerethe pyruvate dehydrogenase complex (PDH) (4,9). in pyruvate brospinal fluid (cells, protein, sugar, cultures, and VDRL), elecdecarboxylase (the first compcnent of this complex (PDC; EC.…”

mentioning

confidence: 99%

“…Then 0.1 ml of this suspension was mixed with 0.01 ml M substrate containing lo5 cpm I4C, incubated at 37" for 1 hr and the radioactive C 0 2 collected without acidification by allowing the reaction mixture to remain at 4O for 10 min after the incubation (3). Palmitate bound to albumin was used in lower concentration (3) and prolonged trypsinization was used when citrate was the substrate (9). Boiled cells were used as the "killed control.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Sensitivity to Carbohydrate in a Patient with Familial Intermittent Lactic Acidosis and Pyruvate Dehydrogenase Deficiency

et al. 1976

View full text Add to dashboard Cite

Pediat. Res. 10: 7 13-720 (1976) Alaninuria metabolic acidosis inborn e r r o r of metabolism pyruvate dehydrogenase deficiency lactic acidosis skin fibrosis m e n t a l retardation Extract diet containing 65% carbohydrates precipitated a severe episode of lactic acidosis and whose two sisters died of the same disorder. His A 9-year-old boy with severe mental and growth retardation and cultured skin fibroblasts proved to be deficient i n PDH activity, diffuse neurologic damage had minimal elevation of blood pyruvate (0.21 mM) and lactate (2.1 mM) on a normal diet hut developed CASE REPORTS life-threatening lactic acidosis (pH 7.14; lactate 21.0 mM) on a diet containing 65% carbohydrates and 15% fat. Subsequently, CASE I blood pyruvate levels rose significantly higher than in 16 control subjects during a glucose tolerance test whereas the glucose levelsThe propositus. JB. was born without complications at term were normal. after a normal pregnancy. Birth weight. length, and head circumTwo sisters died with spontaneous lactic acidosis and an otherwise ference were normal. He was hypoactive and hypotonic and was similar clinical course. ~h~i~ brains at autopsy were severely said to have a "peculiar" odor. Psychomotor development virtualdeficient in myelin but showed no evidence for active &myelination.ly ceased by 3 months of age; growth decelerated at 2 years and Cultured skin fibroblasts from the patient oxidized respiratory infections despite 4 years in a state hospital. Severe normally. ~h~ activity of the pyruvate dehydrogenase complex in neurologic deficits were noted early and were similar to those cell-free extracts (59* 16 pmol/min/mg protein) was significantly described below. less than that for control subjects (389* 35; P < 0.001), but the When seen at age 8.5 years, the patient was severely stunted in activities pyruvate decarboxylase and of the 2-oxoglutarate de-growth, profoundly retarded. had flexion deformities of the hands hydrogenase complex were within the normal range. Pyruvate de-and feet, but had no dysplastic features. Weight was 11.4 kg; hydrogenase levels in extracts of the parents9 cells were midway height, 95 cm; and head circumference. 50 cm. His pulse rate was between those of the patients and the control subjects. ~i~i~~ never found to be below 100. He appeared to hear and see and had experiments, addition of excess cofactor, and studies of activation no evidence of optic atrophy or retinitis pigmentosa. He could not failed to implicate a soluble inhibitor, abnormal binding of co-turn over, sit up. hold his head up, follow, or transfer objects. His factors, or defective activation as causes of the reduced enzyme posture was dystonic with continual choreoathetoid movements. activitv.He tended to hold his muscles rigidly but was profoundly ~h~" data are consistent an inherited defect in the second hypotonic when he relaxed. There were bilateral extensor plantar enzyme of the pyruvate dehydrogenase complex, lipoate acetyl-reflexes. The deep tendon reflexes were normal to slightly in...

show abstract

Section: Discussionsupporting

confidence: 90%