Follow-up of fatty acid β-oxidation disorders in expanded newborn screening era

  • Patrícia JaneiroEmail author
  • Rita Jotta
  • Ruben Ramos
  • Cristina Florindo
  • Fátima V. Ventura
  • Laura Vilarinho
  • Isabel Tavares de Almeida
  • Ana Gaspar
Original Article


Fatty acid β-oxidation (FAO) disorders have a wide variety of symptoms, not usually evident between episodes of acute decompensations. Cardiac involvement is frequent, and severe ventricular arrhythmias are suspected of causing sudden death. Expanded newborn screening (ENS) for these disorders, hopefully, contribute to prevent potentially acute life-threatening events. In order to characterize acute decompensations observed in FAO-deficient cases identified by ENS, a retrospective analysis was performed, covering a period of 9 years. Demographic data, number/type of acute decompensations, treatment, and follow-up were considered. Eighty-three clinical charts, including 66 medium-chain acyl-CoA dehydrogenase deficiency (MCADD), 5 carnitine-uptake deficiency (CUD), 3 carnitine palmitoyltransferase I and II (CPT I/II) deficiency, 5 very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), and 4 multiple acyl-CoA dehydrogenase deficiency (MADD) cases were reviewed. Nineteen patients had acute decompensations (1 CPT I, 1 CPT II, 3 MADD, 14 MCADD). Six patients developed symptoms previously to ENS diagnosis. Severe clinical manifestations included multiple organ failure, liver failure, heart failure, and sudden death. Long-chain FAO disorders had the highest number of decompensations per patient.

Conclusion: Despite earlier diagnosis by ENS, sudden deaths were not avoided and acute decompensations with severe clinical manifestations still occur as well.

What is Known:

Severe ventricular arrhythmias are suspected to cause unexpected death in FAO disorders.

Neonatal screening intends to reduce the incidence of severe metabolic crisis and death.

What is New:

Acute severe decompensations occurred in FAO disorders diagnosed through neonatal screening.

Sudden deaths were not avoided by starting treatment precociously.


Fatty acid ß-oxidation disorders Acute decompensations Sudden death 



Creatine kinase


Creatine kinase muscle and brain subunits


Carnitine palmitoyltransferase I


Carnitine palmitoyltransferase II


Carnitine-uptake deficiency


Dry blood spot


Duchenne muscular dystrophy


Expanded newborn screening


Fatty acid β-oxidation


Long-chain fatty acid oxidation disorders


Multiple acyl-CoA dehydrogenase deficiency


Medium-chain acyl-CoA dehydrogenase deficiency


Refference values


Very long-chain acyl-CoA dehydrogenase deficiency


Authors’ Contributions

The planning, carrying out, and reporting of the work was done by Patrícia Janeiro with guidance from Isabel Tavares de Almeida. Rita Jotta had a major contribution in data collection. Ruben Ramos and Fátima Ventura contributed with biochemical and molecular studies. Laura Vilarinho provided neonatal screening data. Ana Gaspar provided clinical outcome data and contributed in the article review process.

Compliance with ethical statements

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

This article does not contain any studies with human participants or animals performed by any of the authors. For this type of study, formal consent is not required.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Centro de Referência de Doenças Hereditárias do Metabolismo, Departamento de Pediatria MédicaHospital de Santa Maria – CHULNLisbonPortugal
  2. 2.Serviço de Pediatria Médica, Departamento de PediatriaHospital de Santa Maria – CHULNLisbonPortugal
  3. 3.Laboratório de Metabolismos e GenéticaFaculdade de Farmácia da Universidade de LisboaLisbonPortugal
  4. 4.Unidade de Rastreio Neonatal Metabolismo e Genética, Departamento de Genética HumanaInstituto Nacional de Saúde Dr. Ricardo JorgePortoPortugal

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