Liver hepatoblastoma and multiple OXPHOS deficiency in the follow-up of a patient with methylmalonic aciduria

Cosson, M.A.; Touati, Guy; Lacaille, Florence; Valayannnopoulos, V.; Guyot, Charlotte; Verkarre, V.; Chrétien, Dominique; Rabier, Daniel; Münnich, Arnold; Benoist, J.-F.; Keyzer, Yves de; Niaudet, Patrick; Lonlay, Pascale de

doi:10.1016/j.ymgme.2008.06.007

Cited by 33 publications

(36 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Until now, PC deficiency has not been described as a possible cause of secondary MRC deficiency except in one case of holocarboxylase synthetase deficiency [12]. However other diseases with secondary MRC defect have been described including pyruvate dehydrogenase (PDHc) deficiency (OMIM 312170), which is the most frequently reported one [12], fatty acid oxidation defects [13], [14], [15], [16], neonatal hemochromatosis (OMIM 231100) [12], [17], pantothenate kinase deficiency (OMIM 606157) [12], holocarboxylase synthetase deficiency (OMIM 253270) [12], molybdenum cofactor deficiency [9], spino-cerebellar ataxia type 7 (OMIM 164500) [18], [19], Menkes disease (OMIM 309400) [20], [21], Wilson disease (OMIM 277900) [17], OTC deficiency (OMIM 311250) [17], progressive familial intrahepatic cholestasis type 2 (OMIM 601847) [22], hereditary spastic paraparesis type 7 (OMIM 607259) [23], Fanconi–Bickel syndrome (OMIM 227810) [24], autism spectrum disorder (ASD) [25], [26] and more recently organic acidurias [27], [28].…”

Section: Discussionmentioning

confidence: 99%

Pyruvate carboxylase deficiency: An underestimated cause of lactic acidosis

Habarou

Brassier

Rio

et al. 2015

Molecular Genetics and Metabolism Reports

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Pyruvate carboxylase deficiency: An underestimated cause of lactic acidosis

Habarou

Brassier

Rio

et al. 2015

Molecular Genetics and Metabolism Reports

Self Cite

View full text Add to dashboard Cite

show abstract

“…The intermediate prognosis of MMA suggests that toxicity may mainly result from intermediate levels of PA metabolites. Indeed, it has been demonstrated that methylmalonate has no obvious toxicity on respiratory chain [20], yet secondary respiratory chain deficiency has been reported in PA and MMA patients in different tissues [21,22]. …”

Section: Discussionmentioning

confidence: 99%

Long-term neurological outcome of a cohort of 80 patients with classical organic acidurias

Nizon

Ottolenghi

Valayannopoulos

et al. 2013

Orphanet J Rare Dis

View full text Add to dashboard Cite

BackgroundClassical organic acidurias including methylmalonic aciduria (MMA), propionic aciduria (PA) and isovaleric aciduria (IVA) are severe inborn errors of the catabolism of branched-chain amino acids and odd-numbered chain fatty acids, presenting with severe complications.MethodsThis study investigated the long-term outcome of 80 patients with classical organic aciduria (38 with MMA, 24 with PA and 18 with IVA) by integrating clinical, radiological, biochemical and genetic data.ResultsPatients were followed-up for a mean of 14 years [age 3.3-46.3 years]. PA included a greater number of patients with abnormal neurological examination (37% in PA, 24% in MMA and 0% in IVA), lower psychometric scores (abnormal evaluation at age 3 years in 61% of patients with PA versus 26% in MMA and 18% in IVA) and more frequent basal ganglia lesions (56% of patients versus 36% in MMA and 17% in IVA). All patients with IVA presented a normal neurological examination and only 1/3 presented cognitive troubles. Prognosis for MMA was intermediate. Biochemical metabolite analysis excluding acute decompensations revealed significant progressive increases of glycine, alanine and glutamine particularly in PA and possibly in MMA but no correlation with neurological outcome. A significant increase of plasma methylmalonic acid was found in MMA patients with intellectual deficiency (mean level of 199 μmol/L versus 70 μmol/L, p < 0.05), with an estimated significant probability of severe outcome for average levels between birth and age 6 years above 167 μmol/L. Urinary 3-hydroxypropionate (3-HP) levels were significantly higher in PA patients with intellectual deficiency (mean level of 68.9 μmol/mmol of creatinine versus 34.6 μmol/mmol of creatinine, p < 0.01), with an estimated significant probability of severe outcome for average levels between birth and age 6 years above 55 μmol/mmol. As for molecular analysis, prognosis of MMA patients with mutations involving the MMAA gene was better compared to patients with mutations involving the MUT gene.ConclusionPropionic aciduria had the most severe neurological prognosis. Our radiological and biochemical data are consistent with a mitochondrial toxicity mechanism. Follow-up plasma MMA and urinary 3-HP levels may have prognostic significance calling for greater efforts to optimize long-term management in these patients.

show abstract

“…9-33 Twenty-six received an isolated LT, 9-25 7 LKT, 25-29 and 5 KT. [30][31][32][33] Most reports describe single cases and data on long-term outcomes after transplantation are lacking. We report long-term follow-up of 14 patients with MMA who received LKT or LT at a single institution to further the knowledge of longterm prognosis of MMA after organ transplantation.…”

mentioning

confidence: 99%