Fatty acid oxidation disorders are a group of autosomal recessive genetic metabolic disorders characterized by impaired fatty acid metabolism due to the disruption of the transport of the fatty acids to the mitochondria or their beta-oxidation once inside the mitochondria.
There are several types of fatty acid oxidation disorders all caused by a mutation in a different gene. These are medium-chain acyl-CoA dehydrogenase deficiency (MCADD), very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), long-chain 3-hydroxy acyl-CoA dehydrogenase deficiency (LCHAD), trifunctional protein deficiency (TFPD), carnitine palmitoyltransferase type 1 deficiency (CPT1D), carnitine-acylcarnitine translocase deficiency (CACTD), carnitine palmitoyltransferase type 2 deficiency (CPT2D), carnitine transporter deficiency (CTD), short-chain acyl-CoA dehydrogenase deficiency (SCADD), Multiple acyl-CoA dehydrogenase deficiency (MADD), and 3-hydroxyacyl-CoA dehydrogenase deficiency (HADD).1
Of these CPT1D, CACTD, CPT2D, LCHAD, VLCADD, and TFPD are classed as long chain fatty acid oxidation disorders (LCFAOD).
The overall prevalence of all fatty acid oxidation disorders is between 1 in 5,000 and 1 in 10,000 births. However, the prevalence varies greatly by disease type with MCADD being the most prevalent at 1 in 20,000.1
Prevalence by Disease Type
The prevalence of CPT1 deficiency is estimated to be 1 in 500,000. The prevalence of the other two types of diseases characterized by the impairment of the carnitine shuttle, CACT deficiency, and CPT2 deficiency, is very low and they are simply classed as rare.
When taken together, the prevalence of CPT1 deficiency, CACT deficiency, CPT2 deficiency, and CTD is between 1:750,000 to 1:2,000,000.1
This is also the case for TFP deficiency, which is characterized by impaired beta-oxidation of long chain fatty acids.
The prevalence of LCHAD deficiency is thought to be between 1 in 110,000 and 1 in 150,000 births. That of VLCAD deficiency varies between 1:42,500 to 1:120,000.1
Incidence and Prevalence by Geographical Location
The overall incidence of LCFAOD is estimated to be 1 in 9300 in the United States, Australia, and Germany. The incidence is similar in the rest of the world.3
A study published in 2014 in the Journal of Inherited Metabolic Disease showed that Iberia (Portugal and Spain) had one of the highest fatty acid oxidation disorder prevalence in Europe with 1 in 7,914. According to the study, Portugal had the highest reported birth prevalence of fatty acid oxidation disorders at 1 in 6,351. Here too, the type of fatty acid oxidation disorder with the highest prevalence was MCADD with a prevalence of 1 in 8,380. More than 90% of reported cases of MCADD were of Gypsy origin among whom consanguinity is very common, which can explain the high prevalence.4
The reported prevalence of fatty acid oxidation disorders in other countries are as follows: 1 in 12,704 in Austria, 1 in 9,198 in Germany, 1 in 7691 in Denmark, 1 in 8,777 in Italy, 1 in 45,000 in Italy, and 1 in 12,929 in Australia.4
The prevalence is only available for MCADD in Switzerland, United Kingdom, Belgium, the Netherlands, Japan, and Saudi Arabia and are 1 in 11,500, 1 in 10,204, 1 in 15,000, 1 in 9,624, 1 in 51,000, and 1 in 18,293 respectively.4
The incidence of all fatty acid oxidation disorders seems to be lower in Asian populations compared to non-Asian populations and ranges between 0.9 and 4.9 per 100,000 births.5
A study in Singapore reported the incidence of fatty acid oxidation disorders at 15.2 per 100,000 births.6 Another study in China also reported a very high incidence of the disease at 11 per 100,000 births.7 A study in Taiwan calculated the incidence of the diseases at 4.53 per 100,000 births.8
Impact of Newborn Screening on the Reported Incidence
The addition of fatty acid oxidation disorders to newborn screening programs in the United States and other developed countries has increased the detection rate of the diseases.
For example, in Germany, the incidence of all fatty acid oxidation disorders was reported as 3.2 per 100,000 births between 1999 and 2000 where 844,575 patients were screened. Between 2002 and 2015 where 7,510,000 patients were screened, the incidence was reported to be 11.1 per 100,000 births.5
Similarly, the incidence of fatty acid oxidation disorders before the introduction of the disease to newborn screening programs in Australia was reported to be between 0.9 and 3.2 per 100,000. This rate became more than doubled following the introduction of the disease to newborn screening program in 1998 to 8 per 100,000 births.6
- Merritt JL 2nd, Norris M, Kanungo S. Fatty acid oxidation disorders. Ann Transl Med. 2018;6(24):473. doi:10.21037/atm.2018.10.57
- Watson MS, Mann MY, Lloyd-Puryear MA, Rinaldo O, Howell RR. Newborn screening: toward a uniform screening panel and system. Genet Med. 2006;8 Suppl 1(Suppl 1):1S-252S. doi:10.1097/01.gim.0000223891.82390.ad
- Vockley J. Long-chain fatty acid oxidation disorders and current management strategies. Am J Manag Care. 2020;26(7 Suppl):S147-S154. doi:10.37765/ajmc.2020.88480
- Rocha H, Castiñeiras D, Delgado C, et al. Birth prevalence of fatty acid β-oxidation disorders in lberia. JIMD Rep. 2014;16: 89–94. doi:10.1007/8904_2014_324
- Marsden D, Bedrosian CL, Vockley J. Impact of newborn screening on the reported incidence and clinical outcomes associated with medium- and long-chain fatty acid oxidation disorders. Genet Med. 23,816–829 (2021). doi:10.1038/s41436-020-01070-0
- Lim SJ, Tan ES, John CM, et al. Inborn error of metabolism (IEM) screening in singapore by electrospray ionization-tandem mass spectrometry (ESI/MS/MS): an 8 year journey from pilot to current program. Mol Genet Metab. 2014;113(1-2):53-61. doi:10.1016/j.ymgme.2014.07.018
- Yang C-J, Wei N, Li M, et al. Diagnosis and therapeutic monitoring of inborn errors of metabolism in 100,077 newborns from jining city in china. BMC Pediatr. 2018;13;18(1):110. doi:10.1186/s12887-018-1090-2
- Chien Y-H, Lee N-C, Chao M-C, et al. Fatty Acid oxidation disorders in a chinese population in taiwan. JIMD Rep. 2013;11:165-72. doi:10.1007/8904_2013_236
Reviewed by Harshi Dhingra, MD, on 7/1/2021.