Review General Endocrinology

Diagnosis and Clinical Management of

Long-chain Fatty-acid Oxidation Disorders:
A Review
Joshua J Baker1,2 and Barbara K Burton1,2
1. Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA; 2. Northwestern University Feinberg School of Medicine,
Chicago, IL, USA

L
ong-chain fatty-acid oxidation disorders (LC-FAODs) are autosomal recessive inherited metabolic conditions that occur due to
a disruption in the body’s ability to perform mitochondrial beta oxidation. Expanded newborn screening is widening phenotypic
understanding of these disorders, as well improving our knowledge of disease incidence. Management of these disorders is focused on
avoidance of fasting, dietary changes and supplementation with energy sources that bypass the metabolic block. Recent US Food and Drug
Administration approval of triheptanoin has improved the outcome for affected individuals. New research into dietary modifications and
novel pharmacologic therapies continues for these disorders. In this article, we review the major LC-FAODs and their clinical presentation.

Keywords Long-chain fatty-acid oxidation disorders (LC-FAODs) are pan-ethnic, autosomal recessive,
Long-chain fatty-acid oxidation disorders inherited metabolic conditions causing disruption in the processing or transportation of fats into the
(LC-FAODs), beta oxidation, triheptanoin, mitochondria to perform beta oxidation.1 In normal metabolism, long-chain fatty acids are bound
newborn screening, nutrition,
to carnitine within the cytosol of cells, and transported across the mitochondrial membranes.
inborn errors of metabolism
Within the mitochondria, they are then cleaved from carnitine to undergo beta oxidation by a
Disclosures: Barbara K Burton has received complex of enzymes specific to the length of the carbon chain. These enzymes go through cycles
consulting fees and/or honoraria from of beta oxidation until the carbon chain has been reduced to a structure that may feed into the
Ultragenyx Pharmaceutical Inc. Joshua J Baker
has no financial or non-financial relationships or tricarboxylic acid cycle for energy production. This energy source is critical when the body is in a
activities to declare in relation to this article. fasting state, providing energy for skeletal and cardiac muscle, the liver and other tissues.2
Review process: Double-blind peer review.
Compliance with ethics: This study involves Disorders result from defects in the transportation or utilization of these long-chain fats for
a review of the literature and did not involve
any studies with human or animal subjects energy, which become critical when the body has exhausted its glycogen stores.3 Classical
performed by any of the authors. symptoms shared among all disorders include hypoketotic hypoglycaemia, hepatic dysfunction,
Authorship: The named authors meet the International cardiomyopathy, skeletal myopathy, rhabdomyolysis and sudden death.1 However, there is
Committee of Medical Journal Editors (ICMJE) criteria
for authorship of this manuscript, take responsibility wide variability within phenotypes that may range from critical illness in an infant, to exercise
for the integrity of the work as a whole, and have intolerance in an adult. Understanding of these presentations is increasing due to expansion in
given final approval for the version to be published.
testing for these conditions, and a broader understanding of genotype–phenotype correlations.
Access: This article is freely accessible at
touchENDOCRINOLOGY.com © Touch Medical Media 2021 Early recognition of the diagnosis of LC-FAOD is important in optimizing outcomes. Even if patients
Received: 8 March 2021 with LC-FAODs are asymptomatic at presentation, most can be expected to suffer from recurrent
Accepted: 13 April 2021 decompensation during times of acute illness or stress, requiring acute and chronic medical
Published online: 10 September 2021 management.4 In this narrative review we explore the current clinical approach to the diagnosis
Citation: touchREVIEWS in Endocrinology. 2021; and management of LC-FAODs. A subjective literature review was conducted using PubMed, in
17(2):108–11
addition to utilization of current clinical guidelines, with the aim of providing a concise resource for
Corresponding author: Joshua J Baker, Ann & Robert
H Lurie Children’s Hospital of Chicago, Northwestern practicing clinicians and other healthcare professionals treating patients with LC-FAODs.
University Feinberg School of Medicine, 225 E Chicago
Avenue, Chicago, IL, 60661, USA.
E: [email protected] Long-chain fatty-acid oxidation disorders
Systemic primary carnitine deficiency
Support: No funding was received for Systemic primary carnitine deficiency (CDSP), also known as carnitine transport disorder or carnitine
the publication of this article.
uptake disorder, is caused by biallelic variants in SLC22A5.5 This disorder results in a defect in the
transportation of carnitine from the serum into cells. Carnitine is essential in the transportation
of long-chain fats from the cytosol into the mitochondria for beta oxidation. CDSP has a wide
range of clinical prestations. The classic phenotype includes recurrent episodes of hypoketotic
hypoglycaemia, elevated transaminases, hepatomegaly and hypoglycaemia. There is a severe
childhood myopathic form that affects both skeletal and cardiac muscle, with increased risk for
sudden death. Due to the implementation of newborn screening, mild forms have become more
commonly diagnosed, with easy fatiguability or no clinical symptoms reported.6 Since carnitine is
transported from maternal serum across the placenta during pregnancy, there have been many
cases in which low carnitine on newborn screening is actually due to an underlying diagnosis

108 Journal Publication Date: 10 November 2021 TOUC H ME D ICA L ME D IA

 Diagnosis and Clinical Management of Long-chain Fatty-acid Oxidation Disorders: A Review

Table 1: Classical biochemical findings for long-chain fatty-acid oxidation disorders

Disorder Acylcarnitine abnormalities1 Urine abnormalities3,14

CDSP ↓ C0 ↑ Carnitine, nonspecific dicarboxylic aciduria
CPT1A ↑ C0, C0/C16+C18; ↓C2 ↑ Dodecanedioic acid, C12 dicarboxylic acid
CACT ↑ C16, C18, C18:1, C18:2
CPT2 ↑ C16, C18, C18:1, C18:2
VLCAD ↑ C12, C14, C14:1, C16, C18 ↑ Longer-chain dicarboxylic aciduria
LCHAD ↑ C14OH, C16, C16OH, C18OH, C18:1OH ↑ Longer-chain 3-hydroxydicarboxylic acids
C0 = low levels of free carnitine; CACT = carnitine acylcarnitine translocase; CDSP = systemic primary carnitine deficiency; CPT1A = carnitine palmitoyltransferase 1A;
CPT2 = carnitine palmitoyltransferase 2; LCHAD = long-chain 3-hydroxyacyl-CoA dehydrogenase; VLCAD = very long-chain acyl-CoA dehydrogenase.

of CDSP in the mother.7 While these women may be asymptomatic on with the typical hypoketotic hypoglycaemia, hypotonia, myopathy,
diagnosis, they may be at risk for decompensation if not treated during hepatic dysfunction, cardiomyopathy and cardiac arrythmias.
times of stress. In the long-term, patients typically experience recurrent rhabdomyolysis
and may exhibit cardiac disease progression with significant stress. With
Carnitine palmitoyltransferase 1A deficiency the expansion of newborn screening, many more individuals with a milder
Carnitine palmitoyltransferase 1A (CPT1A) encodes for the homonymous phenotype are being identified, with symptoms of skeletal myopathy and
enzyme that resides on the outer mitochondrial membrane.8 Its function rhabdomyolysis not presenting until adolescence or adulthood; some
is to convert long-chain acyl-CoAs to long-chain acylcarnitines, which may remain asymptomatic for life.11 This milder form has now become
can be transported into the mitochondria for beta oxidation. Individuals the most commonly diagnosed phenotype.11
with CPT1A deficiency may present with episodes of hypoketotic
hypoglycaemia, acute liver failure, hepatic encephalopathy and Long-chain 3-hydroxyacyl-CoA dehydrogenase
hyperammonaemia. It differs from the other LC-FAODs in that cardiac deficiency/trifunctional protein deficiency
manifestations are very rare in CPT1A deficiency. Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and trifunctional
protein (TFP) are two disorders that are clinically indistinguishable.
Carnitine acylcarnitine translocase deficiency Molecularly, they can be differentiated through the evaluation of HADHA
Carnitine acylcarnitine translocase is a transporter in the inner and HADHB.1 Most affected patients present in infancy or early childhood
mitochondrial membrane to traffic acylcarnitines into the inner with hypoglycaemia, hepatic dysfunction, cardiomyopathy and sudden
mitochondria and free carnitine back towards cytosol. This condition is death. LCHAD may also present with maternal HELLP (haemolysis,
very rare, with most patients presenting in the neonatal period. Clinical elevated liver enzymes, and a low platelet count) syndrome or acute
presentation includes hypoketotic hypoglycaemia, hepatomegaly, fatty liver of pregnancy when the foetus is affected. Long-term sequelae
hyperammonaemia, myotonia, seizures, cardiomyopathy and respiratory include myopathy, recurrent rhabdomyolysis and exercise intolerance.
distress.1 Mortality is high in the neonatal period. Survivors typically Unique phenotypic features of LCHAD/TFP include peripheral neuropathy
experience recurrent rhabdomyolysis.1 and retinopathy.12 Concern has also been raised for the increased
comorbidities of intellectual disability and autism spectrum disorders in
Carnitine palmitoyltransferase 2 deficiency LCHAD.13 Further research on the underlying mechanism is still required.
The carnitine palmitoyltransferase 2 gene (CPT2) encodes for an inner
mitochondrial membrane protein that cleaves fatty acids from carnitine Diagnosis
to be used in beta oxidation. There are three classical presentations of Biochemical investigations
this disorder. The first is a lethal neonatal form that commonly presents General laboratory findings that may be suggestive of a diagnosis of a
shortly after birth with hypoketotic hypoglycaemia, hepatic dysfunction, LC-FAOD include hypoglycaemia accompanied by a lack of, or decrease
cardiomyopathy, arrhythmias, encephalopathy and seizures. Structural in, ketone production; an elevation in transaminases; or elevations
abnormalities are also seen with dysmorphic facial features, cystic renal in creatine kinase. If a medical provider is suspicious of a LC-FAOD,
dysplasia and neuronal migration defects.9 Survival is rare. The second biochemical testing is the best initial step. Diagnostic laboratory studies
form is an infantile form with recurrent episodes of hypoglycaemia, include plasma total and free carnitine, acylcarnitine profile, urine organic
liver dysfunction, rhabdomyolysis and cardiomyopathy, requiring close acids and, in some cases, urine acylglycines depending on availability.
monitoring and aggressive treatment for life. The third disorder is Table 1 shows the typical biochemical profile for each LC-FAOD.14
characterized primarily by muscle involvement with exercise intolerance
and recurrent episodes of rhabdomyolysis. There is also hypotonia and It is important to consider that a patient, especially one with a mild defect,
weakness during attacks.10 However, many patients are asymptomatic could have a normal biochemical profile in a well-fed state. This is why the
between attacks and some may not present until adulthood. most accurate acylcarnitine profiles for diagnosis are obtained with critical
sample laboratory tests during a period of hypoglycaemia. It should also be
Very long-chain acyl-CoA dehydrogenase deficiency noted that, if there is a severe defect causing significantly low levels of all
Very long-chain acyl-CoA dehydrogenase (VLCAD) is the most common carnitine species, the specific diagnostic abnormality may not be evident
LC-FAOD. It is due to biallelic variants in ACADVL, which encodes until the carnitine has been replenished. The wide use of next-generation
an enzyme involved in the metabolism of acylcarnitines with 14–20 sequencing has made molecular testing relatively inexpensive, enabling
carbons.1 Severely affected patients present in the neonatal period gene-based testing when there is high clinical suspicion.

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Review General Endocrinology

Newborn screening dietary fat be limited to 20–30% of total energy intake.19 The patient’s
Newborn screening is now broadly implemented across all states in severity is used to determine how much energy is from long-chain fat
the USA and in some other countries for LC-FAOD, allowing many versus MCT oil. For example, patients with mild to moderate disease may
patients to be diagnosed before initial presentation.6 Newborn have their calories split 50/50, while those with a severe LC-FAOD would
screening specimens are typically obtained at 24–48 hours of age have a ratio of 2:1 MCTs versus long-chain fat.
when newborns are still in a relatively stressed state from labour and
delivery and may not yet be feeding significant amounts. By the time of The European guidelines allow slightly more liberalization of fats in
follow-up testing, they are typically feeding regularly and acylcarnitine asymptomatic individuals, with fats constituting 30–40% of total energy
abnormalities seen at screening may no longer be evident. Therefore, and only 10–15% from MCTs.15 MCTs work well for LC-FAOD treatment,
the acylcarnitine profile alone cannot be used to rule out the diagnosis because these shorter-chain fats bypass the metabolic defect, are able
of LC-FAOD and must be combined with either molecular or enzymatic to diffuse across the mitochondrial membrane without the requirement
testing. Early diagnosis, while improving the outcome, does not of transporters, and then undergo fewer rounds of beta oxidation to
prevent risk of further decompensations. Furthermore, a normal feed into the tricarboxylic acid cycle for energy production.15 Essential
newborn screen does not completely rule out the possibility of an fatty acids should also be monitored and appropriately supplemented.
LC-FAOD, so any patient who presents clinically with suggestive Current dietary therapy guidelines are largely consensus driven.
findings should have diagnostic testing. Carnitine supplementation is controversial. Docosahexanoic acid is
recommended for LCHAD/TFP, and new research suggests consideration
Newborn screening programmes are giving us a broadened view of of supplementation in other LC-FAODs as well.20 Despite this long-standing
phenotype and a more accurate understanding of the incidence of these therapeutic guidance, even patients with well-controlled symptoms
disorders. The current incidence estimate for all FAODs is 0.9–15.2 per experience recurrent hospitalizations and high morbidity/mortality rates.21
100,000, but there may be significant geographic variability.15 The newborn
screening programme in Tianjin, China, screened 220,443 infants from Triheptanoin
May 2013 to December of 2018, and diagnosed 15 individuals with FAODs, Triheptanoin is a highly purified, 7-carbon chain triglyceride that has
with the most common being CDSP.16 A group from Italy also recently recently been approved by the US Food and Drug Administration (FDA)
published their 5-year screening data, from February 2014 to April 2019. for the treatment of LC-FAODs in the USA. The metabolism of odd-chain
They quote a new regional incidence of 1:4,316 newborns with FAODs, carbon species allows for broad replenishment of tricarboxylic acid
with 20 confirmed diagnoses.17 Continued global investigations will cycle intermediates by supplying both acetyl CoA and propionyl CoA,
further our understanding of the overall prevalence of these disorders. differing from C8 oils that supply acetyl CoA only. In clinical studies, the
most common side effects were gastrointestinal: diarrhoea, abdominal
Acute management pain/discomfort and vomiting, which are the same side effects seen
Patients with LC-FAODs suffer from recurrent acute metabolic with standard MCTs.22 The use of triheptanoin differs slightly from typical
decompensations that require emergent medical intervention. Medical US dietary management using MCTs. While traditionally, C8 MCT oil was
providers should counsel patients on the avoidance of triggers of dosed at 15–25% of daily caloric intake, the recommended dose range of
decompensation, such as prolonged fasting, excess activity and triheptanoin is 25–35% of daily caloric intake.23
emotional stress. However, other stressors, such as intercurrent illnesses
or surgery, may not be preventable.4 The severity of the disorder will Clinical trials have demonstrated that triheptanoin reduces the incidence
often correlate with the timing of initial decompensation, with the most of major clinical events (defined as hypoglycaemia, cardiomyopathy or
severe disorders presenting with significant cardiac or hepatic symptoms rhabdomyolysis) and hospitalizations in patients with LC-FAODs.20 In an
shortly after birth. During times of acute illness, patients should shorten independent, double-blind, controlled study, Gillingham et al. randomized
fasting times and increase carbohydrate caloric intake with frequent 32 patients with LC-FAOD to receive either triheptanoin or C8 oil, both of
glucose-containing beverages. If patients have severe symptoms, poor oral which being 20% of the subjects’ daily caloric intake.24 They found that
intake or vomiting, it is recommended that they seek immediate medical the triheptanoin group had a 7.4% increase in left ventricular injection
attention and be started on dextrose-containing intravenous fluids. Ten fraction, and a 20% decrease in left ventricular wall mass. Patients also
percent dextrose solution (D10) at 1.5 times maintenance is usually experienced a lower heart rate for the same amount of work when
sufficient to stop catabolism; however, this should be titrated with the help compared to their C8 counterparts.
of a metabolic provider.18 Laboratory studies typically include liver function
testing and creatine kinase to assess response to therapy. Additional Macronutrients
medical interventions will be illness or stressor specific. Once the patient is While the implementation of triheptanoin has been a major
in their normal state of health, dextrose fluids should be weaned gradually advancement in the management of patients with LC-FAODs, there
to prevent a rebound catabolic state from the withdrawal of calories. has also been new research regarding the macronutrient composition
of dietary management. The diet traditionally consists of an increase in
Chronic management carbohydrate intake to maintain caloric needs and prevent catabolism of
Dietary management fatty acids. Gillingham et al. recently conducted a 4-month trial in which
Management of LC-FAODs typically consists of avoidance of prolonged they compared two groups: one with increased dietary carbohydrate
periods of fasting, dietary restriction of long-chain fats, supplementation intake and the other with increased dietary protein. Both groups had
with medium-chain triglycerides (MCTs), and a moderate increase roughly 20% of daily caloric intake from fat.25 The high carbohydrate
in carbohydrate intake. Small snacks may be appropriate prior to any group were prescribed daily caloric intake of 11–13% protein and
activity or to provide increased calories at times of physical exercise, or 64–74% carbohydrate, while the high protein group were prescribed daily
at bedtime prior to a longer fasting period. As per the Genetic Metabolic caloric intake of 25–28% protein and 50–56% carbohydrate. Although
Dieticians International guidelines, it is typically recommended that the study was small in size (n=13), they found that the high-protein

110 TOUC HR EV I EW S I N EN D OCRINOLOG Y

 Diagnosis and Clinical Management of Long-chain Fatty-acid Oxidation Disorders: A Review

group had increased blood levels of short-chain acylcarnitines, reduced Conclusion

intrahepatic lipid content, and maintained lean body mass while the Recent years have seen significant improvements in our ability to
high-carbohydrate group lost lean body mass. diagnose and manage LC-FAODs. Both implementation of newborn
screening and expansion of next-generation sequencing has
Investigational therapies allowed us to broaden our understanding of the known phenotypes.
There are a number of novel approaches for the treatment of LC-FAOD While these conditions are relatively rare, collectively they are one of
being investigated in clinical or preclinical studies. Reneo Pharmaceuticals the most common metabolic defects. It is critical for all healthcare
is currently recruiting for its phase Ib study on a peroxisome providers to include these in their differential diagnoses, and not
proliferator-activated receptor delta agonist, which, in cell culture miss a highly treatable condition.1,3 As LC-FAODs are increasingly
systems, increased fatty-acid oxidation and mitochondrial energy diagnosed, further advances in treatment and management are
metabolism (updates on their study are available on ClinicalTrials.gov).26 important to reduce the morbidity and mortality associated with
Work by Bleeker et al. demonstrated improvement in patients with these disorders. Triheptanoin has provided a significant new treatment
VLCAD with the supplementation of nutritional ketones as an alternative option in the USA. Further research and novel therapies will likely
fuel source prior to exercise.27 Advancements continue in the realm of improve disease management and quality of life for individuals
gene therapy for common LC-FAODs.28 affected by LC-FAODs. q

1. Vockley J, Longo N, Andresen B, Bennet M. Mitochondrial Fatty 11. Pena LD, van Calcar SC, Hansen J, et al. Outcomes and dietary therapy upon visual function in children with long-chain
Acid Oxidation Defects. In: Sarafoglou K, Hoffmann G, Roth K genotype-phenotype correlations in 52 individuals with VLCAD 3-hydroxyacyl CoA dehydrogenase and trifunctional protein
(eds.). Pediatric Endocrinology and Inborn Errors of Metabolism. deficiency diagnosed by NBS and enrolled in the IBEM-IS deficiency. Mol Genet Metab. 2005;86:124–33.
Second Edition, New York: McGraw-Hill Education, 2017;125–44. database. Mol Genet Metab. 2016;118:272–81. 21. Vockley J. Long-chain fatty acid oxidation disorders and current
2. El-Gharbawy A, Vockley J. Inborn errors of metabolism with 12. Fletcher AL, Pennesi ME, Harding CO, et al. Observations management strategies. Am J Manag Care.
myopathy: defects of fatty acid oxidation and the carnitine regarding retinopathy in mitochondrial trifunctional protein 2020;26(Suppl. 7):S147–54.
shuttle system. Pediatr Clin North Am. 2018;65:317–35. deficiencies. Mol Genet Metab. 2012;106:18–24. 22. Vockley J, Burton B, Berry G, et al. Effects of triheptanoin
3. Nyhan WL, Barshop BA, Ozand PT. Introduction to Disorders 13. Strandqvist A, Haglind CB, Zetterström RH, et al. (UX007) in patients with long-chain fatty acid oxidation
of Fatty Acid Oxidation. In: Nyhan WL, Barshop BA, Ozand PT Neuropsychological development in patients with long-chain disorders: results from an open-label, long-term extension
(eds.). Atlas of Metabolic Disease. New York: Hodder Arnold, 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency. study. J Inherit Metab Dis. 2021;44:253–63.
2005;241–5. JIMD Rep. 2016;28:75–84. 23. Vockley J, Longo N, Madden M, et al. Dietary management
4. Spiekerkoetter U, Lindner M, Santer R, et al. Management 14. Merritt JL 2nd, Norris M, Kanungo S. Fatty acid oxidation and major clinical events in patients with long-chain fatty acid
and outcome in 75 individuals with long-chain fatty acid disorders. Ann Transl Med. 2018;6:473. oxidation disorders enrolled in a phase 2 triheptanoin study.
oxidation defects: results from a workshop. J Inherit Metab Dis. 15. Marsden D, Bedrosian CL, Vockley J. Impact of newborn Clin Nutr ESPEN. 2021;41:293–8.
2009;32:488–97. screening on the reported incidence and clinical outcomes 24. Gillingham MB, Heitner SB, Martin J, et al. Triheptanoin versus
5. Li FY, El-Hattab AW, Bawle EV, et al. Molecular spectrum of associated with medium- and long-chain fatty acid oxidation trioctanoin for long-chain fatty acid oxidation disorders: a
SLC22A5 (OCTN2) gene mutations detected in 143 subjects disorders. Genet Med. 2021;23:816–29. double blinded, randomized controlled trial. J Inherit Metab Dis.
evaluated for systemic carnitine deficiency. Hum Mutat. 16. Wang S, Leng J, Diao C, et al. Genetic characteristics and 2017;40:831–43.
2010;31:E1632–51. follow-up of patients with fatty acid β-oxidation disorders 25. Gillingham MB, Elizondo G, Behrend A, et al. Higher dietary
6. Wilcken B. Fatty acid oxidation disorders: outcome and through expanded newborn screening in a Northern Chinese protein intake preserves lean body mass, lowers liver lipid
long-term prognosis. J Inherit Metab Dis. 2010;33:501–6. population. J Pediatr Endocrinol Metab. 2020;33:683–90. deposition, and maintains metabolic control in participants with
7. El-Hattab AW, Li FY, Shen J, et al. Maternal systemic primary 17. Maguolo A, Rodella G, Dianin A, et al. Diagnosis, genetic long-chain fatty acid oxidation disorders. J Inherit Metab Dis.
carnitine deficiency uncovered by newborn screening: characterization and clinical follow up of mitochondrial fatty 2019;42:857–69.
clinical, biochemical, and molecular aspects. Genet Med. acid oxidation disorders in the new era of expanded newborn 26. ClinicalTrials.gov. A Study of the Safety of REN001 in Patients
2010;12:19–24. screening: a single centre experience. Mol Genet Metab Rep. with Fatty Acid Oxidation Disorders. ClinicalTrials.gov Identifier:
8. Knottnerus SJG, Bleeker JC, Wüst RCI, et al. Disorders of 2020;24:100632. NCT03833128. Available at: https://clinicaltrials.gov/ct2/show/
mitochondrial long-chain fatty acid oxidation and the carnitine 18. Aldubayan SH, Rodan LH, Berry GT, Levy HL. Acute illness NCT03833128 (accessed 22 April 2021).
shuttle. Rev Endocr Metab Disord. 2018;19:93–106. protocol for fatty acid oxidation and carnitine disorders. 27. Bleeker JC, Visser G, Clarke K, et al. Nutritional ketosis improves
9. Boemer F, Deberg M, Schoos R, et al. Diagnostic pitfall in Pediatr Emerg Care. 2017;33:296–301. exercise metabolism in patients with very long-chain acyl-CoA
antenatal manifestations of CPT II deficiency. Clin Genet. 19. Rohr F. Nutrition Management of Fatty Acid Oxidation dehydrogenase deficiency. J Inherit Metab Dis. 2020;43:787–99.
2016;89:193–7. Disorders. In: Bernstein L, Rohr F, Helm J (eds.). Nutrition 28. Zieger M, Keeler AM, Flotte TR, et al. AAV9 gene replacement
10. Bonnefont JP, Djouadi F, Prip-Buus C, et al. Carnitine Management of Inherited Metabolic Diseases. New York: therapy for respiratory insufficiency in very-long chain
palmitoyltransferases 1 and 2: biochemical, molecular and Springer, 2015;271–82. acyl-CoA dehydrogenase deficiency. J Inherit Metab Dis.
medical aspects. Mol Aspects Med. 2004;25:495–520. 20. Gillingham MB, Weleber RG, Neuringer M, et al. Effect of optimal 2019;42:870–7.

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