FAOD In Focus for HCP

Energy in the Balance

Long-chain fatty acid oxidation disorders (LC-FAOD) are characterized by an unbalanced metabolism that impairs energy production.1,2

LC-FAOD are a group of rare, often severe, and life-threatening autosomal recessive disorders that result from defective enzymes involved in the transport and catabolism of long-chain fatty acids (LCFAs).1-4
LC-FAOD include the following types4:

Carnitine palmitoyltransferase I (CPT I) deficiency3,5

CAUSE

Mutation in the CPT1A gene; prevents long-chain fatty acids from being transported into the cells’ mitochondria for breakdown

ESTIMATED INCIDENCE

1:750,000 to
1:2,000,000

CLINICAL PRESENTATION

Birth to 18 months

liver damage, low blood sugar (hypoglycemia) with low ketones (hypoketotic), seizures

Carnitine-acylcarnitine translocase (CACT) deficiency3,6,7

CAUSE

Mutation in the SLC25A20 gene; prevents long-chain fatty acids from being transported into the cells’ mitochondria for breakdown

ESTIMATED INCIDENCE

1:750,000 to
1:2,000,000

CLINICAL PRESENTATION

Neonatal/infantile presentation

low blood sugar (hypoglycemia) with low ketones (hypoketotic), high ammonia levels in blood (hyperammonemia), enlarged liver (hepatomegaly), heart muscle damage (cardiomyopathy) with or without irregular heartbeat (arrhythmia), breathing difficulties, muscle weakness, seizures

Later onset

has been reported with milder symptoms

Carnitine palmitoyltransferase II (CPT II) deficiency3,5

CAUSE

Mutation in the CPT2 gene; prevents long-chain fatty acids from being transported into the cells’ mitochondria for breakdown

ESTIMATED INCIDENCE

1:750,000 to
1:2,000,000

CLINICAL PRESENTATION

Neonatal/infantile presentation

low blood sugar (hypoglycemia) with low ketones (hypoketotic), heart muscle damage (cardiomyopathy)

Adolescent/young adult presentation

recurrent muscle breakdown (rhabdomyolysis)

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency3,5

CAUSE

Mutation in the ACADVL gene; prevents long-chain fatty acids from being broken down via fatty acid beta-oxidation

ESTIMATED INCIDENCE

1:85,000

CLINICAL PRESENTATION

Overall

heart muscle damage (cardiomyopathy) at any age

Early childhood presentation

low blood sugar (hypoglycemia) with low ketones (hypoketotic), high ammonia levels in blood (hyperammonemia)

Adolescent/adult presentation

recurrent muscle breakdown (rhabdomyolysis) and myoglobin in the urine (myoglobinuria), which causes kidney injury

Trifunctional protein (TFP) deficiency3,5

CAUSE

Mutations in both the HADHA and HADHB genes, leads to defects in the entire TFP complex. Prevents long-chain fatty acids from being broken down via fatty acid beta-oxidation

ESTIMATED INCIDENCE

1:750,000

CLINICAL PRESENTATION

Overall

severe nerve damage (peripheral neuropathy), retina damage (retinopathy)

Early childhood presentation

similar to LCHAD deficiency but often more severe: low blood sugar (hypoglycemia) with low ketones (hypoketotic), high ammonia levels in blood (hyperammonemia)

Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency3,5

CAUSE

Mutation in the HADHA gene, which encodes for a subunit of TFP. Prevents long-chain fatty acids from being broken down via fatty acid beta-oxidation

ESTIMATED INCIDENCE

1:250,000

CLINICAL PRESENTATION

Overall

skeletal muscle damage (myopathy) with or without recurrent muscle breakdown (rhabdomyolysis), nerve damage (peripheral neuropathy), retina damage (retinopathy)

Early childhood presentation

low blood sugar (hypoglycemia) with low ketones (hypoketotic), high ammonia levels in blood (hyperammonemia)

Adolescent/adult presentation

recurrent muscle breakdown (rhabdomyolysis) and myoglobin in the urine (myoglobinuria), which causes kidney injury

Patients with LC-FAOD face difficult challenges and substantial medical burdens

When energy balance is disrupted, chronic symptoms and acute episodes burden patients1,8-11

When LC-FAOD is Suspected

Confirmatory genetic testing may be appropriate for anyone with a suspected LC-FAOD diagnosis1

Up-to-date information on LC-FAOD

Explore selected publications and resources that provide valuable insights and support for patients and caregivers in English and Spanish

When LC-FAOD is Suspected

Confirmatory genetic testing may be appropriate for anyone with a suspected LC-FAOD diagnosis1

Up-to-date information on LC-FAOD

Explore selected publications and resources that provide valuable insights and support for patients and caregivers

Up-to-date information on LC-FAOD

Explore selected publications and resources that provide valuable insights and support for patients and caregivers

References

1. Knottnerus SJG, Bleeker JC, Wüst RCI, et al. Rev Endocr Metab Disord. 2018;19(1):93-106. 2. Wajner M, Amaral AU. Biosci Rep. 2015;36(1):e00281. 3. Lindner M, Hoffmann GF, Matern D. J Inherit Metab Dis. 2010;33(5):521-526. 4. Wanders RJ, Ruiter JP, IJLst L, Waterham HR, Houten SM. J Inherit Metab Dis. 2010;33(5):479-494. 5. Vockley J. Am J Manag Care. 2020;26(suppl 7):S147-S154. 6. Pennisi EM, Garibaldi M, Antonini G. J Clin Med. 2018;7(12):E472. 7. Vitoria I, Martín-Hernández E, Peña-Quintana L, et al. JIMD Rep. 2015;20:11-20. 8. Saudubray JM, Martin D, de Lonlay P, et al. J Inherit Metab Dis. 1999;22(4):488-502. 9. Shekhawat PS, Matern D, Strauss AW. Pediatr Res. 2005;57(5 Pt 2):78R-86R. 10. Vockley J, Burton B, Berry GT, et al. Mol Genet Metab. 2017;120(4):370-377. 11. Siddiq S, Wilson BJ, Graham ID, et al. Orphanet J Rare Dis. 2016;11(1):168.

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