Inborn Errors of Fatty

Acids
Outline
• Introduction
• Therapy
• Types of FAOD
• MCADD • Nutritional Management
• LCHADD for all FOADs
• VLCADD
• Conclusion
• Diagnosis
• Prevalence • Reference
Introduction
 β - Oxidation of Fatty
Acids
Fatty acids present in digested food materials
they undergo beta-oxidation in the
mitochondria.

Fatty acid beta-oxidation provides energy after

the body has used up its stores of glucose and
glycogen.

This oxidation typically occurs during periods of

extended fasting or illness when caloric intake
is reduced, and energy needs are increased.

Deficiencies in these enzymes are linked to

genetic disorders involving fatty acid oxidation
(i.e. metabolic disorders)
Both parents are carriers of an
abnormal gene, when two
abnormal genes unite the child will
have a FAOD.
chance that chance of child

25% each child will

have a FAOD 75% being a carrier, NOT
having the disorder
at all
 There are many types of
FAODs but these are the
most common:
Types of • MCADD Medium Chain Acyl coA
FAOD Dehydrogenase deficiency
• LCHADD Long Chain 3- Hydroxy
Acyl coA deficiency
• VLCADD Very Long Chain Acyl CoA
Dehydrogenase deficiency
 Medium-chain acyl-CoA
dehydrogenase (MCAD) deficiency

MCADD is a condition that prevents the

body from converting certain fats to
energy, particularly during periods
without food – fasting.
 SYMPTOMS
VOMITTING
LETHARGIC

HYPOGLYCEMIA
 COMPLICATIONS

COMA and
SEIZURES
SUDDEN DEATH

BRAIN DAMAGE AND

BREATHING DIFFICULTY LIVER PROBLEM
MCADD Screening NBS :
Plasma
Acyl carnitine abnormalities should be confirmed
samples

shows Elevations of :
Urine
acylglycine 1. propionylglycine
testing 2. suberylglycine
3. hexanoylglycine

DNA mutation of the ACADM gene

• www.youtube.com/watch?v=k7YoJU0qyLk
 The mitochondrial trifunctional protein
LCHADD heterooctomer includes the four alpha
and TFPD and four beta subunits encoded by the
HADHA and HADHB genes.

The mitochondrial trifunctional protein

complex has three enzymatic activities:
1. long-chain enoyl-CoA hydratase,
2. long-chain 3-hydroxy acyl-CoA
dehydrogenase,
3. 3-ketoacyl-CoA thiolase
 COMPLICATIONS
• Cardiomyopathy
• Hypoketotic Hypoglycemia
• Liver dysfunction
• Cholestasis
• Rhabdomyolysis b e i n g se e n d u e
l o p m e n t a re n o w
t h a n d d e v e D
Improved grow i t ut i o n o f t h e ra p y i n L C H A D
S a nd e a r l y in s t o r t a l i ty a r e
to N B m o rb i d it y a n d m
r e v e n ti o n o f a l l
although p p a ti e n t s
e c ia l ly i n T F P D
incomplet e , e s p
 Two types of VLCADD deficiency:
1. Complete deficiency: present with
severe cardiomyopathy and death in
the first few days of life.
VLCADD 2. Partial deficiency: may only have
recurrent hypoketotic hypoglycemia
or presentation in adolescence or
adulthood with myopathy and/or
rhabdomyolysis.
VLCADD Diagnosis :
• detected post-mortem or NBS results

• Plasma acyl carnitines, sequencing of

ACADVL is recommended for confirmation

• Urine organic acid analysis

Diagnosis:
Newborn screening through tandem mass spectrometry

Blood, urine, skin fibroblasts, amniocytes (from amniotic

fluid) and muscle and liver tissue are some of the specimens
analyzed. 

The diagnostic tests often include an acylcarnitine profile,

urine organic acid analysis, carnitine levels and enzyme
assays in fibroblasts

The acylcarnitine profile with whole blood on a ‘PKU card’ is

the most direct approach for diagnosis of most of the FODs.
 There is an estimated collective incidence of 1 in 5,000–
10,000 births, although the individual prevalence varies
significantly.

Genetic If one child is diagnosed with an FOD, their siblings should

(Epidemiology) also be tasted, even if they are asymptomatic.

Prevalence:
Repetition risk for each pregnancy will then have a 1 in 4 chance
of a child being affected.
1 in 2 chance of being an unaffected carrier;
1 in 4 chance of being unaffected and not a carrier
 Prevalence of FAODs in
UAE

There were 136,049 live births (citizens) from all emirates in 2011–2014.
Fifty-five infants were diagnosed with IEM during this period, giving a
prevalence of 1 in 2,474

7 (13%) had fatty acid oxidation disorders

Therapy
Nutrition Management for all FAODs:
Feed the baby with an infant formula in which most long chain fat is
replaced by MCT

avoidance of fasting :
• Infants need to be fed every 3 hours with no more than 4 hours of fasting age 0–4
months.
• After infancy it is important that children avoid fasting for more than 10–12 hours
overnight.

aggressive treatment during illness(increased metabolic stress):

• Providing oral or enteral carbohydrate-rich fluids every 3–4 hours with mild to moderate illness.
• Intravenous fluids with 10% dextrose with appropriate electrolytes are provided during times of
illness, poor oral intake, or when fasting for surgery.

supplementation of carnitine
• Carnitine supplementation may only be helpful if secondary carnitine deficiency is found.
References
• FOD Support [https://fodsupport.org/diagnosis/]
• NCBI [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331364/]
• NIH GARD [https://rarediseases.info.nih.gov/diseases/6867/lchad-
deficiency]
• Ultragenyx [https://www.ultragenyx.com/pipeline/UX007-faod/]
• FOAD In Focus [https://www.faodinfocus.com/treatment-options/]