Journal of Inherited Metabolic Disease

, Volume 36, Issue 5, pp 795–803 | Cite as

Clinical and biological features at diagnosis in mitochondrial fatty acid beta-oxidation defects: a French pediatric study of 187 patients

  • Julien Baruteau
  • Philippe Sachs
  • Pierre Broué
  • Michèle Brivet
  • Hendy Abdoul
  • Christine Vianey-Saban
  • Hélène Ogier de Baulny
Original Article

Abstract

Introduction

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.

Conclusion

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.

Abbreviations

AFLP

Acute fatty liver of pregnancy

ALAT

Alanine aminotransferase

CACT

Carnitine acylcarnitine translocase

CMP

Cardiomyopathy

CPTI

Carnitine palmitoyl transferase I

CPTII

Carnitine palmitoyl transferase II

CTD

Carnitine transporter defect

FAO

Fatty acid β-oxidation

FAODs

FAO defects

GGT

Gamma-glutamyl transpeptidase

HELLP syndrome

Hemolysis–liver–low platelets

KB

Ketone bodies

LCHAD

Long-chain 3-hydroxyacyl-CoA dehydrogenase

LCHADD

LCHAD deficiency

MADD

Multiple acyl-CoA dehydrogenase deficiency

MCAD

Medium-chain acyl-CoA dehydrogenase deficiency

MCADD

MCAD deficiency

MTP

Mitochondrial trifunctional protein

NSP

Newborn screening program

PPAR-α

Peroxisome proliferator activated receptor alpha

PT

Prothrombin time

ROS

Reactive oxygen species

VLCAD

Very-long-chain acyl-CoA dehydrogenase

VLCADD

VLCAD deficiency

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Copyright information

© SSIEM and Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Julien Baruteau
    • 1
    • 7
  • Philippe Sachs
    • 2
  • Pierre Broué
    • 1
  • Michèle Brivet
    • 3
  • Hendy Abdoul
    • 4
  • Christine Vianey-Saban
    • 5
  • Hélène Ogier de Baulny
    • 6
  1. 1.Hépatologie Pédiatrique et Maladies MétaboliquesHôpital des Enfants–CHU ToulouseToulouseFrance
  2. 2.Réanimation Pédiatrique–Hôpital Robert Debré–AP-HPParisFrance
  3. 3.Biochimie Métabolique–Hôpital de Bicêtre–AP-HPLe Kremlin BicêtreFrance
  4. 4.Epidémiologie Clinique–Hôpital Robert Debré–AP-HPParisFrance
  5. 5.Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal–CBPE–CHU LyonBronFrance
  6. 6.Neurologie Pédiatrique et Maladies Métaboliques–Hôpital Robert Debré–AP-HPParisFrance
  7. 7.Hépatogastroentérologie Pédiatrique et Maladies MétaboliquesToulouse cedex 9France

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