Clinical and biological features at diagnosis in mitochondrial fatty acid beta-oxidation defects: a French pediatric study of 187 patients.
BACKGROUND
Mitochondrial fatty acid β-oxidation defects (FAODs) are a group of severe inherited metabolic diseases, most of which can be treated with favorable prognosis following diagnosis. A description of the broad range of phenotypes resulting from these defects remains incomplete, and for this study, we sought to investigate the semiology at diagnosis in a country without a newborn screening program for FAODs.


METHODS
Using a retrospective French multicentre study, we analyzed 187 children aged <6 years at diagnosis with FAOD confirmed by enzymatic and/or molecular analyses. Clinical and biological parameters at diagnosis were assessed to screen liver, heart, neurological, and muscle symptoms. Information concerning the long-term prognosis was also collected.


RESULTS
Predominant hepatic symptoms were observed in 89 % of patients regardless of the underlying defect. The most frequent symptoms observed were hepatomegaly (92 %), increased blood alanine aminotransferase (ALAT) level (82 %), and steatosis (88 %). Other frequent features included Reye syndrome (49 %), increased gamma-glutamyltranspeptidase (GGT) (37 %), and liver failure (27 %). Extrahepatic features were often associated in the foreground. Hypoglycemia (75 %), neurological (64 %), muscle (61 %), or cardiac features (55 %) [as either cardiomyopathy (47 %) or arrhythmias (31 %)] were frequently documented. Hemodynamic events (41 %) were represented by shock (31 %) or sudden death (35 %). Hyperammonemia (73 %) and hyperlactacidemia (57 %) were the two main biochemical features. Total, very-long-chain acyl-CoA dehydrogenase (VLCADD), long-chain 3-hydroxyacylCoA dehydrogenase (LCHADD), and medium-chain acyl-CoA dehydrogenase (MCADD) deficiency mortality rates were 48 %, 60 %, 63 %, and 20 % respectively.


CONCLUSIONS
This study presents clinical features of a large cohort of patients with FAODs in a country without neonatal screening for FAODs. Our results highlight liver as the main organ involved at diagnosis regardless of age at diagnosis, classical phenotype (i.e., cardiac, hepatic, or muscular), or enzyme deficiency. Although steatosis may be observed in various inherited metabolic defects, it is a reliable indicator of FAOD and should prompt systematic screening when the diagnosis is suspected. The poor long-term prognoses reported are a strong argument for inclusion of FAODs in newborn screening programs.
Hépatologie Pédiatrique et Maladies Métaboliques, Hôpital des Enfants-CHU Toulouse, Toulouse, France. jbaruteau@yahoo.fr
Julien
J
Baruteau
Philippe
P
Sachs
Pierre
P
Broué
Michèle
M
Brivet
Hendy
H
Abdoul
Christine
C
Vianey-Saban
Hélène
H
Ogier de Baulny
D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency* / Q000378:metabolism; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency*; D002648:Child; D002675:Child, Preschool; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D012189:Retrospective Studies
D005227:Fatty Acids; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain