Pyruvate Carboxylase Deficiency Disease

An autosomal recessive metabolic disorder caused by absent or decreased PYRUVATE CARBOXYLASE activity, the enzyme that regulates gluconeogenesis, lipogenesis, and neurotransmitter synthesis. Clinical manifestations include lactic acidosis, seizures, respiratory distress, marked psychomotor delay, periodic HYPOGLYCEMIA, and hypotonia. The clinical course may be similar to LEIGH DISEASE. (From Am J Hum Genet 1998 Jun;62(6):1312-9)

Also Known As:

Networked: 30 relevant articles (0 outcomes, 2 trials/studies)

Disease Context: Research Results

Related Diseases

1.	Lactic Acidosis
2.	Propionic Acidemia
3.	Hyperammonemia
4.	Hyperlysinemias (Hyperlysinemia)
5.	Infantile Spasms (West Syndrome)

Experts

1.	De Meirleir, Linda: 2 articles (01/2013 - 12/2002)
2.	Lehman, Anna M: 1 article (03/2014)
3.	Eydoux, Patrice: 1 article (03/2014)
4.	Preece, Mary Anne: 1 article (03/2014)
5.	Bhavsar, Amit P: 1 article (03/2014)
6.	Santra, Saikat: 1 article (03/2014)
7.	Nguyen, Hien: 1 article (03/2014)
8.	Zhang, Lin-Hua: 1 article (03/2014)
9.	Waheed, Abdul: 1 article (03/2014)
10.	Ukpeh, Henry: 1 article (03/2014)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Pyruvate Carboxylase Deficiency Disease:

1.	Pyruvate CarboxylaseIBA 03/01/1984 - "We propose that the different clinical presentation of human pyruvate carboxylase deficiency is a manifestation of two different mutations in the pyruvate carboxylase gene, one that results in the synthesis of a relatively inactive pyruvate carboxylase protein CRM(+ve) and one that results in the lack of expression of the gene in the form of a recognizable protein CRM(-ve)." 06/30/1983 - "Pyruvate carboxylase activity was investigated in cultured fibroblasts from a patient shown to have hepatic pyruvate carboxylase deficiency. " 05/25/1983 - "Four out of 5 cell lines from patients with classical pyruvate carboxylase deficiency (less than 5% of normal activity) labeled with this technique displayed a normal band in the position of pyruvate carboxylase while one cell line showed complete absence of any labeled protein in this area. " 01/01/1980 - "The activity of pyruvate carboxylase in the crude homogenate from cultured human fibroblasts was 0.76 +/- 0.12 nmol/min per mg protein, while the activity in cultured amniotic fluid cells was 0.66 +/- 0.17 nmol/min per mg protein, suggesting the possibility of prenatal diagnosis of pyruvate carboxylase deficiency." 04/01/2005 - "Considering that pyruvate carboxylase is a key enzyme for anaplerosis, besides the new perspectives brought by anaplerotic therapies in those rare pyruvate carboxylase deficiencies, this therapeutic trial also emphasizes the possible extended indications of triheptanoin in various diseases where the citric acid cycle is impaired."
2.	CarbonIBA 01/01/1986 - "Oxidative studies using a number of radioactive carbon-labelled substrates on intact cultured skin fibroblasts from a patient with pyruvate carboxylase deficiency revealed dysfunction of the Krebs cycle. " 10/01/1987 - "Pyruvate carboxylase deficiency was previously reported to be the biochemical lesion in a yeast mutant, designated pyc, which cannot utilize ethanol, acetate, pyruvate, aspartate, or oxaloacetate as the sole carbon source [C. "
3.	triheptanoinIBA 03/01/2014 - "Unsuccessful treatment of severe pyruvate carboxylase deficiency with triheptanoin." 04/01/2005 - "Considering that pyruvate carboxylase is a key enzyme for anaplerosis, besides the new perspectives brought by anaplerotic therapies in those rare pyruvate carboxylase deficiencies, this therapeutic trial also emphasizes the possible extended indications of triheptanoin in various diseases where the citric acid cycle is impaired."
4.	Pyruvic Acid (Pyruvate)IBA 03/01/1982 - "The relationship between SNE and a defect in pyruvate metabolism is under discussion, and it is concluded that the general assumption that pyruvate carboxylase deficiency is the cause of SNE is not in agreement with our results or the present literature. " 01/01/2013 - "Pyruvate dehydrogenase and pyruvate carboxylase deficiency are the most common disorders in pyruvate metabolism. " 08/01/1981 - "A seven-year-old girl with slowly progressive motor neurological impairment and high levels of lactate and pyruvate in blood and cerebrospinal fluid was found to have severe hepatic pyruvate carboxylase deficiency. " 12/01/2002 - "This article describes defects in pyruvate metabolism (pyruvate carboxylase deficiency, pyruvate dehydrogenase deficiency) and Krebs cycle defects such as fumarase deficiency. " 10/01/1987 - "Pyruvate carboxylase deficiency was previously reported to be the biochemical lesion in a yeast mutant, designated pyc, which cannot utilize ethanol, acetate, pyruvate, aspartate, or oxaloacetate as the sole carbon source [C. "
5.	Biotin (Vitamin H)FDA Link 04/01/2005 - "Biotin-unresponsive pyruvate carboxylase deficiency type B was diagnosed. " 12/03/1999 - "Biotin-unresponsive pyruvate carboxylase deficiency was diagnosed. " 05/09/1983 - "This method should be a rapid and accurate method for the diagnoses of the various carboxylase deficiencies, particularly isolated pyruvate carboxylase deficiency in individuals with lactic acidosis, as well as for the assessment of biotin responsiveness in these patients." 01/01/1987 - "The French and North American phenotypes of pyruvate carboxylase deficiency, correlation with biotin containing protein by 3H-biotin incorporation, 35S-streptavidin labeling, and Northern blotting with a cloned cDNA probe." 05/25/1983 - "[3H]biotin-labeled proteins in cultured human skin fibroblasts from patients with pyruvate carboxylase deficiency."
6.	Urea (Carbamide)FDA LinkGeneric 11/01/1985 - "Pyruvate-carboxylase deficiency with urea cycle impairment." 03/06/2014 - "CA-VA deficiency should therefore be added to urea cycle defects, organic acidurias, and pyruvate carboxylase deficiency as a treatable condition in the differential diagnosis of hyperammonemia in the neonate and young child." 02/01/2002 - "Defects of lysine metabolism are rare, but hyperlysinemia is a concomitant of many inborn errors of metabolism, including urea cycle abnormalities, pyruvate carboxylase deficiency and L-2-hydroxyglutaric aciduria. "
7.	Aspartic Acid (Aspartate)FDA Link 12/03/1999 - "Treatment of pyruvate carboxylase deficiency with high doses of citrate and aspartate." 08/01/1981 - "A patient with pyruvate carboxylase deficiency in the liver: treatment with aspartic acid and thiamine." 10/01/1987 - "Pyruvate carboxylase deficiency was previously reported to be the biochemical lesion in a yeast mutant, designated pyc, which cannot utilize ethanol, acetate, pyruvate, aspartate, or oxaloacetate as the sole carbon source [C. "
8.	OxaloacetateIBA 11/01/1976 - "This unusual metabolic pattern may be assumed to result from decreased oxaloacetate synthesis as a result of pyruvate carboxylase deficiency, and impairment of oxaloacetate dependent mitochondrial redox shuttles. " 10/01/1987 - "Pyruvate carboxylase deficiency was previously reported to be the biochemical lesion in a yeast mutant, designated pyc, which cannot utilize ethanol, acetate, pyruvate, aspartate, or oxaloacetate as the sole carbon source [C. "
9.	Lactic AcidFDA LinkGeneric 08/01/1981 - "A seven-year-old girl with slowly progressive motor neurological impairment and high levels of lactate and pyruvate in blood and cerebrospinal fluid was found to have severe hepatic pyruvate carboxylase deficiency. " 03/01/2002 - "Acetazolamide can produce severe lactic acidosis with an increased lactate-to-pyruvate ratio, ketosis with a low beta-hydroxybutyrate-to-acetoacetate ratio, and a urinary organic acid profile typical of pyruvate carboxylase deficiency. "
10.	3-Hydroxybutyric Acid (beta-Hydroxybutyric Acid)IBA 03/01/2002 - "Acetazolamide can produce severe lactic acidosis with an increased lactate-to-pyruvate ratio, ketosis with a low beta-hydroxybutyrate-to-acetoacetate ratio, and a urinary organic acid profile typical of pyruvate carboxylase deficiency. "

Therapies and Procedures

1.	Liver Transplantation 09/01/2002 - "Pyruvate carboxylase deficiency--insights from liver transplantation."
2.	Diet Therapy (Therapy, Diet) 04/01/2005 - "Pyruvate carboxylase deficiency: clinical and biochemical response to anaplerotic diet therapy."