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Susan C. Winter, MD
Carnitine is a natural substance important to the
transport of fat into the mitochondria where it is "burnt" for energy.
Carnitine is also important in removing the biochemical "ashes"
remaining after the fat is metabolized to energy. It does this by
binding to the biochemical ashes and carries them out of the mitochondria
and then out of the body as carnitine bound "ashes" (acylcarnitine
derivatives) dissolved in the urine. Carnitine is eaten in the diet
in red meats and dairy products, including breast milk, and is also
made in the body from breaking down muscle protein and converting
it to carnitine.
As with all natural substances, deficiency can occur.
Carnitine deficiency is nearly always secondary to other problems
and may often be due to more than one factor. In infants and
small children with small muscle masses, carnitine deficiency can
develop easily due to poor muscle protein supplies for synthesis.
These small children are very dependent on dietary carnitine for
their supply. If the diet is inadequate from generalized malnutrition,
or due to a special formula not supplemented with carnitine or Total
Parenteral Nutrition (TPN) that is unsupplemented, deficiency can
develop within weeks. Children and adults with gastrointestinal
malabsorption, such as those with cystic fibrosis or chronic diarrhea,
can develop deficiency. Increased loss of carnitine from the blood
or urine can occur with hemo - or peritoneal dialysis as it is a
small chemical and comes out in the dialysis fluids. Carnitine deficiency
is also seen in children with kidney disorders affecting the reabsorption
of needed chemicals from the filtered urine, renal Fanconi syndrome.
In children with genetic metabolic disorders affecting fat oxidation,
carnitine deficiency occurs due to a massive excretion of carnitine
in the urine bound to the unburnt "ashes" of fat metabolism.
These unburnt fats attached to carnitine can be detected in the
urine of these patients in high levels and this is the basis
of the acylcarnitine derivative testing being used for newborn screening
using the tandem MS-MS method.
Carnitine deficiency is associated with many symptoms.
Since the deficiency is nearly always secondary to another disease
process, the symptoms are often those of the primary disease plus
additional problems that can be reversed with carnitine replacement
therapy. Deficiency of carnitine results in decreased energy
available to muscle and muscle weakness and low muscle tone.
Growth of muscle, and thus weight gain, also requires energy and
the child with carnitine deficiency usually has failure to thrive.
Carnitine deficiency can affect the cardiac muscle and result in
poor cardiac contractions (cardiomyopathy). Energy is important
to brain function and abnormalities of brain function can be seen
including convulsions, lethargy, irritability, and even coma.
These children are very susceptible to infections and
with the frequent infections they often show signs of deterioration
of mental and physical status. Liver function may worsen and liver
failure may occur. In children with genetic metabolic diseases,
carnitine deficiency can be life threatening due to the inability
to excrete the unburnt "ashes" left over from incomplete fuel burning.
These accumulating ashes are toxic and poison the individual.
Without carnitine to take these toxins out, the individual may die
or suffer irreversible damage.
Carnitine is available as a medication and is approved
by the FDA for treating secondary deficiency due to metabolic
diseases. In the USA, only one company, Sigma-tau Pharmaceuticals,
Inc., sells pharmaceutical grade L-carnitine (Carnitor®) that is
available through prescription. Oral L-carnitine is available
as a liquid with 100 milligrams of carnitine in each milliliter
and as a tablet with 330 milligrams of carnitine per tablet.
Intravenous L-carnitine is also available in vials each containing
1 gram in 5 milliliters of solution. Oral carnitine is poorly
absorbed and only about ¼ of what is swallowed is taken into the
body. The rest is excreted in the stool. This can result in
diarrhea, stomach upsets and in about 5% of people, a very fishy
odor caused by certain bacteria in the bowel of some people converting
carnitine to trimethylamines. Intravenous carnitine is fully
available for body use as it bypasses the bowel absorption problems
and for this reason is the preferred route of administration
in children in life threatening crisis. Doses of carnitine used
are variable and range from 50 to 600 milligrams/kg/day with oral
carnitine and 25 to 300 milligrams/Kg/day with IV carnitine. Higher
doses are usually used in children and adults with serious metabolic
disorders during times of metabolic stress and decompensations.
Complications of long term or short-term carnitine
treatment reported have been few and not serious. The body
odor due to trimethylamines can be treated by taking
a low dose of an antibacterial substance such as metronidazole
to kill off the bacteria making the trimethylamines. The gastrointestinal
upset and diarrhea is often short lived and usually improves
if the dose is lowered or given with food or more frequently.
With IV carnitine, the medication may burn if infused too quickly
and may cause reversible pain and irritation if it gets under the
skin (interstitial).
Treatment of fatty acid oxidation defects with
L-carnitine has been shown to be safe and, especially during the
times of metabolic stress, life saving. Theoretical concerns
regarding cardiac arrythmias in children with long chain fat metabolism
defects have never been substantiated and no ill effects have been
reported in this group of patients. Many children with long chain
defects have been shown to reverse serious complications such as
cardiomyopathy on carnitine therapy. In general, carnitine therapy
has markedly improved the health and life style of children with
fatty acid oxidation defects.
Susan C. Winter, MD
Medical Director, Medical Genetics/Metabolism
Valley Children's Hospital
Madera, CA
winter2571@aol.com
[*Please note that not ALL children/adults with
an FOD are treated with carnitine supplementation. EACH child/adult
should be medically evaluated (i.e. is there a documented carnitine
deficiency, are seizure meds being taken that can deplete carnitine,
etc) to determine if this treatment is appropriate for their specific
disorder and medical situation. DLG]
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