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BIOCHEMISTRY
SBK3013
2015/2016
CARNITINE
DEFICIENCY
CASE :
A teenage boy was brought to a hospital as he complaints that
he always get too tired when asked to participate in the any of
school activities. The doctor found muscle weakness in the
boys arms and legs. From the muscle biopsy, the lab pathologist
found that greatly elevated amount of triglycerides esterified
with primary long fatty acid chain. They also found
significant presence of lipid vacuoles in the muscle biopsy.
What causes this symptoms?
Carnitine ?
Carnitine is the quaternary ammonium compound biosynthesized from the
amino acids lysine and methionine.
Carnitine produced by ?
Liver and kidneys, but mostly located in the
voluntary muscle and cardiac muscles.
Carnitine deficiency?
Do you know what is carnitine deficiency?
Function of Carnitine
The amino acid carnitine is required for the transport of long-chain fatty acyl
coenzyme A (CoA)
esters from the intermembraneous space in the mitochondria into
mitochondrial matrix , where
they are oxidized for produce energy by breaking down the lipids.
Transports toxic or waste compounds out of cellular organelle to prevent
accumulation.
Convert fat into energy - by transports of fatty acids into the mitochondria
Types of carnitine ?
1. Primary carnitine deficiency : Genetic disorder of the cellular
carnitinewhere the transport system that usually with symptoms of
cardiomyopathy, skeletal muscle weakness and hypoglycemia.
2. Secondary carnitine deficiency : Shows in the certain disorder such as
chronic renal failure or under certain condition which using certain
antibiotic. It can reduce the carnitine absorption and increase its excretion.
Gene mutation
Gene Mutation ?
Mutation :
- SLC22A5 gene : give instruction to make OCTN2 protein to transport
the carnitine.
- Result of the mutation : an absent or dysfunction of OCTN2 proteins
- Create a premature stop signal in the instructions for making the
OCTN2 protein, resulting in an abnormally short, nonfunctional
protein. Other mutations change single protein building blocks
(amino acids) in the OCTN2 protein.
http://ghr.nlm.nih.gov/gene/SLC22A5
SECONDARY CARNITINE
Symptoms carnitine
1. Severe brain dysfunction (encephalopathy)
deficiency
2. Fatigue
3. Lipid storage myopathy
4. Hyperammonia (metabolic disturbance by excess of ammonia in blood)
5. Hypoglycemia (low blood sugar)
6. Vomitting
7. Fatty liver
8. Muscle weakness
9. Myoglobinuria (presence of myoglobin in urine)
10. Cardiomyopathy (weakened and enlarged heart)
Treatment
Better diagnosis to allow for earlier identification of at-risk individuals
and earlier
treatment
Continued examination of the role of exercise and diet in metabolic
diseases
Development of enzyme replacement therapies
Development of gene therapies.
Avoidance of fasting and strenuous exercise
Dietary interventions, based on cause
1. L-carnitine
The main treatment for CTD is lifelong use of L-carnitine. This is a safe and
natural substance that
helps body cells make energy. It also helps the body get rid of harmful wastes.
L-carnitine can
reverse the heart problems and muscle weakness that happen in children with
CTD.
Your doctor will decide whether or not your child needs L-carnitine. Unless you
are advised
otherwise, use only L-carnitine prescribed by your doctor. Do not use Lcarnitine without
checking with your doctor.
Your metabolic doctor and dietician will give you an appropriate feeding plan
for your infant.
Your doctor will also give you a sick day plan tailored to your childs needs for
you to follow
during illnesses or other times when your child will not eat.
Your metabolic doctor will continue to advise you on how often your child
should eat as he or she
gets older. When they are well, many teens and adults with CTD can go
without food for up to 12
hours without problems. The other treatments usually need to be continued
throughout life.
3. Diet
Sometimes, in addition to L-carnitine treatment, a low-fat, high carbohydrate food plan is
recommended. Any diet changes should be made under the guidance of a dietitian familiar
with CTD. Ask your doctor whether your child needs to have any changes in his or her diet.
4. If your baby has CTD, call your doctor at the start of any illness
Always call your healthcare provider when your baby has any of the following:
poor appetite
low energy or excessive sleepiness
vomiting
diarrhea
an infection
a fever
persistent muscle pain or weakness