Carnitine Deficiency

• What is Carnitine?
 Carnitine is an amino acid that is

required for the transport of long-chain
fatty acids into the mitochondria, the site
of beta-oxidation of fatty acids.
 About 25 percent of the carnitine
required by the body is produced by the
liver and kidneys, while the rest is
derived from dietary intake.
Eg: red meat, poultry, fish and dairy
products.
 Most of the carnitine in the body is
• Mitochondrial membrane protein that converts long-
chain fatty acyl-CoA molecules to their corresponding
acylcarnitine molecules.
• The resulting acylcarnitines are then available for

transport into the mitochondrial matrix where they
can undergo fatty acid oxidation.
• Mitochondrial fatty acid oxidation by the liver provides

an alternative source of fuel when glycogen reserves
are depleted by fasting.
• The pathway fuels ketogenesis for metabolism in

peripheral tissues that cannot oxidize fatty acids.
• A condition that prevents the body
from converting certain fats called
long-chain fatty acids into energy,
particularly during periods without
food (fasting)
• People with this disorder have a

faulty enzyme that disrupts
carnitine's role in processing long-
chain fatty acids.
• Three phenotypes of CPT1A deficiency are recognized
and suspected based on the following findings:
– Hepatic encephalopathy. Individuals (typically

children) present with the laboratory findings of
hypoketotic hypoglycemia and sudden onset of liver
failure and hepatic encephalopathy precipitated by
fasting or fever. The presentation is similar to that seen
in Reye syndrome.
– Adult-onset myopathy. In a single individual of Inuit

origin who was homozygous for the p.Pro479Leu
mutation,the presenting feature was a history of
exercise-induced sudden-onset muscle cramping with no
indication of hypoglycemia or hepatic failure.
– Acute fatty liver of pregnancy. Fetal homozygosity

for CPT1A deficiency has been associated with acute
fatty liver of pregnancy.
• Hypoketotic Hypoglycemia
• low levels of ketones(products of fat breakdown that
are used for energy)
• low blood sugar (hypoglycemia)
• Enlarged liver(hepatomegaly)
• Muscle weakness
• Elevated levels of carnitine in the blood

mutations in the CPT1A gene
production of a defective version of

an enzyme called carnitine
palmitoyltransferase I
long-chain fatty acids from food and fats

stored in the body cannot be transported
into mitochondria to be broken down and
processed
excessive levels of long-chain fatty acids

may build up in tissues, damaging the
liver, heart, and brain
• condition has an autosomal recessive
inheritance pattern
• Treatment of manifestations
– prompt treatment of hypoglycemia with
intravenous 10% dextrose
• Agents/circumstances to avoid
– prolonged fasting
– potentially hepatotoxic agents such as
valproate and salicylate
• Prevention of primary manifestations
– To prevent hypoglycemia, adults need a high-
carbohydate, low-fat diet to provide a constant
supply of carbohydrate energy and medium-
chain triglycerides to provide approximately
one-third of total calories (C6-C10 fatty acids
do not require the carnitine shuttle for entry
into the mitochondrion
– infants should eat frequently during the day
and have cornstarch continuously at night
– fasting should not last more than 12 hours
during illness
– surgery, or medical procedures
• Prevention of secondary complications
– Prevention of hypoglycemia reduces the
risk of related neurologic damage
• Surveillance
– Pregnant female carriers should be
monitored for acute fatty liver of pregnancy
– Individuals with CPT1A deficiency should
have testing of liver enzymes (AST, ALT,
ALP) and liver function (including PT and
PTT) at clinic appointments even when
asymptomatic and during periods of
reduced caloric intake and febrile illness
 Manifests with a decrease of carnitine levels in
plasma or tissues, may be associated with
genetically determined metabolic conditions,
acquired medical conditions, or iatrogenic states.
 Disorders of the carnitine cycle or disorders of
fatty acid beta-oxidation can cause secondary
carnitine deficiency via several mechanisms.
Block in fatty acid oxidation contributes to the
accumulation of acyl-CoA intermediates.
Transesterification with carnitine leads to the
formation of acylcarnitine and the release of free
CoA. These acylcarnitines are excreted readily in
the urine. They inhibit carnitine uptake at the
level of the carnitine transporter in renal cells,
causing increased carnitine losses in the urine
and systemic secondary depletion of carnitine.
 Other genetic conditions that are
associated
with Fanconi syndrome (eg, Lowe
syndrome,
cystinosis) may present with secondary
carnitine deficiency because of

increased
renal losses of carnitine.
 Lysinuric protein intolerance is
associated with
an increased excretion of lysine in the
urine,
 Acquired medical conditions may affect
carnitine homeostasis. Cirrhosis or
chronic
renal failure may impair the
biosynthesis of
carnitine. Diets with low carnitine
content
(eg, lacto-ovo–vegetarian diet) or
malabsorption syndromes may cause
secondary carnitine deficiency.
 It also may be observed in conditions of
increased catabolism present in
patients with
critical illness. Increased losses of
carnitine in the
urine, which occur in renal tubular
 Preterm neonates are at risk for
developing
carnitine deficiency because they have
impaired reabsorption of carnitine at
the level
of the proximal renal tubule and
immature
carnitine biosynthesis.
 Iatrogenic causes of secondary
carnitine
deficiency include several drugs
associated
Symptoms of this disease are commonly
provoked by prolonged exercise or periods
without food.
episodic muscle pain
Patients with organic acidemia may present
with crises consisting of hypoglycemia,
ketoacidosis, and hyperammonemia
Patients with respiratory chain defects or
mitochondrial disorders may present with abnormal
fatigability and lactic acidosis associated with
exertion
The symptoms in newborn are not completely
defined.
 Tandem mass spectrometric
measurement of
serum/plasma acylcarnitines is an
initial
screening test. Definitive diagnosis is
usually
made by detection of reduced CPT
enzyme
activity. Molecular genetic testing of
CPT2,
the only gene known to be associated
with CPT
 Therapy in secondary carnitine deficiency to
replenish carnitine and treat the primary
metabolic defect with specific diet and other
supplements, such as riboflavin, glycine, or
biotin
 Restriction of lipid intake
 Avoidance of fasting situations
 Dietary modifications including replacement of
long-chain with medium-chain triglycerides
supplemented with L-carnitine
 Specific protein-restricted diets in patients
with aminoacidopathies and organic acidemias

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• What is Carnitine?

 Carnitine is an amino acid that is

• The resulting acylcarnitines are then available for

• Mitochondrial fatty acid oxidation by the liver provides

• The pathway fuels ketogenesis for metabolism in

• People with this disorder have a

– Hepatic encephalopathy. Individuals (typically

– Adult-onset myopathy. In a single individual of Inuit

– Acute fatty liver of pregnancy. Fetal homozygosity

• Elevated levels of carnitine in the blood

production of a defective version of

long-chain fatty acids from food and fats

excessive levels of long-chain fatty acids

carnitine deficiency because of

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