Februari 2012
24
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VLCADD – Latest Evidence
Very Long Chain Acyl-CoA Dehydrogenase Deficiency
Very Long Chain Acyl-CoA Dehydrogenase Deficiency (VLCADD, MIM 201475) is an autosomal
recessive disorder in the fatty acid oxidation.
1,2
It is due to a defect in the ACADVL gene (located at
chromosome 17p13) which causes a deficiency of the very long chain acyl-CoA dehydrogenase
enzyme (VLCAD, EC 1.3.99.13). As a result the oxidation of very long acyl-CoA esters (with a chain
length of 14 to 20 carbons) cannot take place. This leads to accumulation of very long acyl-CoA
esters in addition to an energy shortage. Especially during periods of prolonged fasting or exercise,
the fatty acid oxidation falls short relative to the energy needs and toxic metabolites accumulate.
2-
4
The (LCT-restricted, MCT-enriched) dietary therapy, has in some patients a positive effect on the
cardiac dysfunction
5,6
and on the exercise intolerance
7
.
Diagnostic procedures consist of acylcarnitine profiles (increase of long-chain acylcarnitines,
predominantly C14:1), measurement of VLCAD activity in cultured fibroblasts or lymfocytes
(
reduced activity) and mutation analysis of the ACADVL gene.
4,8
Since the introduction of the newborn screening for VLCADD the estimated prevalence is 1 in
31.500.
9
The prevalence in the Netherlands is estimated at 1 in 80.000.
Treatment
Diet
Prevention of catabolic (fasting) stress is the most important component of the treatment. The
maximum fasting interval depends on both age and weight, with a maximum of 12 hours. The diet
for VLCADD consists of a general fat restriction (max 30% percentage of total energy intake)
Furthermore and if needed LCT-restriction (max 20-30% of total fat intake and MCT
supplementation (most stringent in symptomatic infants).
1,10,11
The strict reduction of long-chain fat in the diet requires supplementation of essential long-chain
fatty acids and monitoring of the fat-soluble vitamins.
10
The use of uncooked cornstarch at bedtime might be considered as a slowly released form of
glucose.
1
Emergency protocol
In case of an acute episode the following measures are recommended:
11,12
∙ Asses potential precipitants for metabolic decompensation (dehydration, fever, infection)
∙ If the patient is in a poor condition check blood glucose, electrolytes, blood gas, ammonia and
liver function tests.
∙ Start continuous glucose infusion in case of insufficient (oral) intake, vomiting, dehydration,
hypoglycaemia, metabolic acidosis or decreased alertness.
∙ Correct hypoglycaemia and/or metabolic acidosis.
∙ Use intravenous glucose fluid with adequate electrolyte levels.
∙ Treat precipitating factors to minimize further catabolism.
∙ Increase glucose infusion if the patient fails to improve.
∙ Check for cardiac symptoms (disturbed rhythm or cardiomyopathy) ECG, chest X-ray and/or
cardiac echo.
Prevention of metabolic decompensation
-
Avoid triggers
Triggers for metabolic decompensation such as fasting, dehydration, high long chain fats diet and
irritation of the myocardium (cardiac catheterization) should be avoided.
4