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Pyruvate carboxylase deficiency An underestimated cause of lactic acidosis
- Source :
- Molecular Genetics and Metabolism, Molecular Genetics and Metabolism, Elsevier, 2015, 2, pp.25-31. ⟨10.1016/j.ymgmr.2014.11.001⟩, Molecular Genetics and Metabolism, 2015, 2, pp.25-31. ⟨10.1016/j.ymgmr.2014.11.001⟩, Molecular Genetics and Metabolism Reports, Vol 2, Iss C, Pp 25-31 (2015), Molecular Genetics and Metabolism Reports
- Publication Year :
- 2015
- Publisher :
- HAL CCSD, 2015.
-
Abstract
- International audience; Pyruvate carboxylase (PC) is a biotin-containing mitochondrial enzyme that catalyzes the conversion of pyruvate to oxaloacetate, thereby being involved in gluconeogenesis and in energy production through replenishment of the tricarboxylic acid (TCA) cycle with oxaloacetate. PC deficiency is a very rare metabolic disorder. We report on a new patient affected by the moderate form (the American type A). Diagnosis was nearly fortuitous, resulting from the revision of an initial diagnosis of mitochondrial complex IV (C IV) defect. The patient presented with severe lactic acidosis and pronounced ketonuria, associated with lethargy at age 23 months. Intellectual disability was noted at this time. Amino acids in plasma and organic acids in urine did not show patterns of interest for the diagnostic work-up. In skin fibroblasts PC showed no detectable activity whereas biotinidase activity was normal. We had previously reported another patient with the severe form of PC deficiency and we show that she also had secondary C IV deficiency in fibroblasts. Different anaplerotic treatments in vivo and in vitro were tested using fibroblasts of both patients with 2 different types of PC deficiency, type A (patient 1) and type B (patient 2). Neither clinical nor biological effects in vivo and in vitro were observed using citrate, aspartate, oxoglutarate and bezafibrate. In conclusion, this case report suggests that the moderate form of PC deficiency may be underdiagnosed and illustrates the challenges raised by energetic disorders in terms of diagnostic work-up and therapeutical strategy even in a moderate form.
- Subjects :
- medicine.medical_specialty
Secondary mitochondrial respiratory chain
[SDV]Life Sciences [q-bio]
Case Report
03 medical and health sciences
0302 clinical medicine
Endocrinology
Secondary mitochondrial respiratory chain defects
Internal medicine
Genetics
medicine
Citrate synthase
Biotinidase activity
Molecular Biology
lcsh:QH301-705.5
defects
030304 developmental biology
0303 health sciences
lcsh:R5-920
biology
Pyruvate carboxylase deficiency
Lactic acidosis
medicine.disease
3. Good health
Pyruvate carboxylase
PC deficiency
[SDV] Life Sciences [q-bio]
Gluconeogenesis
lcsh:Biology (General)
biology.protein
Bezafibrate
Severe lactic acidosis
Oxoglutarate dehydrogenase complex
lcsh:Medicine (General)
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 10967192 and 10967206
- Database :
- OpenAIRE
- Journal :
- Molecular Genetics and Metabolism, Molecular Genetics and Metabolism, Elsevier, 2015, 2, pp.25-31. ⟨10.1016/j.ymgmr.2014.11.001⟩, Molecular Genetics and Metabolism, 2015, 2, pp.25-31. ⟨10.1016/j.ymgmr.2014.11.001⟩, Molecular Genetics and Metabolism Reports, Vol 2, Iss C, Pp 25-31 (2015), Molecular Genetics and Metabolism Reports
- Accession number :
- edsair.doi.dedup.....a1228a55f54117f8fab7e2f125dfc793