Name
PYRUVATE CARBOXYLASE DEFICIENCY
DESCRIPTION
DETAIL
AN AUTOSOMAL RECESSIVE DISEASE ( RARE ) D.D. : - LACTIC ACIDOSIS - METABOLIC ACIDOSIS* HIGH SERUM LACTATE & PYRUVATE LEVELS WITH OR WITHOUT A LACTIC ACIDURIA SUGGESTS AN INBORN ERROR OF ENERGY METABOLISM. AN INCREASED LACTATE TO PYRUVATE RATIO IS CHARACTERISTIC OF CITRIC ACID CYCLE DISORDERS. THIS RATIO MAY PARTICULARLY ELEVATED DURING PERIODS OF CRISIS, SUCH AS ILLNESS OR METABOLIC STRESS. * HYPOGLYCEMIA MAY OCCUR DURING FASTING MUCH EARLIER THAN IN OTHER DISORDERS. * MEASUREMENT OF SERUM AMINO ACIDS REVEALS : - HYPERALANINEMIA DUE TO PYRUVATE SHUNTING - HYPERCITRULLINURIA & HYPERLYSINEMIA FROM A METABOLIC BLOCK IN UREA CYCLE DUE TO LOW ASPARTIC ACID - LOW ASPARTIC ACID IS DUE TO DEFICIENCY OF OXALOACETATE PRECURSOR * HYPERAMMONEMIA FROM POOR AMMONIA DISPOSAL & DECREASED UREA CYCLE FUNCTION * ABNORMAL ENZYME FUNCTION CAN BE DETECTED BY FUNCTIONAL ASSAY PERFORMED ON LEUKOCYTES, FIBROBLASTS OR PROPERLY PRESERVED TISSUE SAMPLES * SEVERE FORM OF DISEASE CAN BE DIAGNOSED BY DEMONSTRATING ABSENCE OF PC MRNA OR SPECIFIC CROSS-REACTING MATERIAL * CSF SHOW ELEVATED LACTATE & PYRUVATE LEVELS. GLUTAMINE IS MARKEDLY REDUCED WHILE GLUTAMIC ACID & PROLINE LEVELS ARE ELEVATED * MRI BRAIN - IN NEONATAL PERIOD SHOW VENTRICULAR DILATATION, CEREBRAL, CORTICAL & WHITE MATTER ATROPHY OR PERIVENTRICULAR WHITE MATTER CYSTS * MRI OF INFANTS WITH PROGRESSIVE NEUROLOGIC SYMPTOMS SHOW SYMMETRIC CYSTIC LESIONS & GLIOSIS IN CORTEX, BASAL GANGLIA, BRAIN STEM OR CEREBELLUM &/OR GENERALISED HYPOMYELINATION
TYPENOTES
Treatments are aimed at stimulating the pyruvate dehydrogenase complex (PDC) and providing alternative fuels. Correction of the biochemical abnormality can reverse some symptoms, but central nervous system damage progresses regardless of treatment. " The PDC can provide an alternative pathway for pyruvate metabolism. PDC activity can be optimized by cofactor supplementation with thiamine and lipoic acid and administration of dichloroacetate. Increased pyruvate metabolism through this pathway can help reduce the pyruvate and lactate levels. " " Biotin supplementation is administered to help optimize the residual enzyme activity, but it is usually of little use. " " Citrate supplementation reduces acidosis and provides the needed substrate in the citric acid cycle. " " Aspartic acid supplementation allows the urea cycle to proceed and reduces the ammonia level. " " One patient has been reported to be treated successfully with continuous nocturnal gastric drip-feeding with uncooked cornstarch. " " Triheptanoin has reportedly reversed hepatic failure and biochemical abnormalities in one case by presumably providing a source of acetyl-CoA and anaplerotic propionyl coenzyme A (propionyl-CoA). However, life expectancy was not prolonged. Surgical Care Orthotopic liver transplantation has reversed the biochemical abnormalities in one patient. Diet " Diet has a small effect on outcome. " " A high-carbohydrate, high-protein diet may help to maintain an anabolic state and prevent activation of gluconeogenesis. Further Inpatient Care " Acute decompensation during illness requires admission to the hospital and management of the acidosis with hydration and intravenous bicarbonate. " " The patient must be supplied with adequate carbohydrates. Further Outpatient Care " Lactate levels should be closely monitored. " " A dietary log should be completed to help evaluate dietary manipulations and to ensure compliance. " " An informational statement that describes the child's disorder and the appropriate medical treatment for the disorder in an emergency setting should be carried by the parents at all times. Prognosis " Although diet manipulation and supplementation of substrates and cofactors can reverse some of the biochemical abnormalities, neurologic abnormalities progress and demise within the first 6 months of life is the rule. " " PCD is inherited in an autosomal recessive manner. Enzyme activity of cultured chorionic villus cells can be determined in time for early termination of the pregnancy. Patient Education " The patient and the parents should be well educated on the factors that elicit a crisis and the early signs of decompensation. DRUG TEATMENT : 1.
RELATED DISEASE
Not Available Disease
DISEASE
INVESTIGATION
COMPLETE BLOOD COUNT, CSF EXAMINATION, MRI