Very Long chain Acyl-CoA Dehydrogenase Deficiency

Introduction
Very long-chain acyl-CoA Dehydrogenase Deficiency(VLCADD) is an autosomal recessive
disorder of fatty acid oxidation resulting in an inability to breakdown long-chain fatty acids
for ketone and ATP synthesis (see figure). Clinical symptoms are often triggered by
prolonged fasting, infection or exercise. It is treated with diet and supplemental carnitine.

Clinical Features
Neonatal
Hypertrophic cardiomyopathy
Hypoketotic hypoglycemia
Hepatic encephalopathy
Seizures
Sudden death
Infancy/childhood
Hypoketotic hypoglycemia
Hepatic encephalopathy
Sudden death

Diagnosis
Newborn screen
Tandem mass spectrometry diagnosis on the basis of elevated long-chain
  acyl carnitines, notably C14-carnitine and C16-carnitine.
Confirmation
Repeat newborn screen
Plasma acylcarnitines (elevated long-chain acylcarnitine)
Urinary organic acids (dicarboxylic aciduria)
Definitively by reduced palmitoyl-CoA dehydrogenase activity in cultured fibroblasts

Treatment
Treatment for VLCADD includes a low fat, high carbohydrate diet supplemented with
medium chain triglyceride (MCT) oil and avoidance of fasting by regular feeding
during the day and limitation of overnight fasting, corn starch is often mixed into the
evening formula or milk. The duration of overnight fasting depends on the age of the
child. Infants and young children may be more subject to sudden death than older
children and should not go without carbohydrate intake longer than 4 hours for the first 4
months of life, no longer than 6 hours for ages 4-8 months and no longer than 8 hours
thereafter. Adequate treatment can prevent or reverse the clinical symptoms in VLCADD,
including the cardiomyopathy. Carnitine administration may be provided in the case of
a low blood carnitine level. Some centers treat with carnitine regardless of the blood level.
No side effects of carnitine are known other than a fishy odor and some loosening of
stools when given in very high doses (usually not necessary in VLCADD).

Situations that risk metabolic decompensation
Children with SCADD may be clinically asymptomatic. Metabolic decompensation can be
triggered by the catabolic processes that occur in the course of an infection,
post-immunization or with a prolonged period of fasting. Lethargy, vomiting,
tachypnea or apnea, with or without hypoglycemia, are typical clinical features. During
acute illnesses or periods of poor oral intake a regular feeding schedule is particularly
important, as often as every four hours around the clock. If the child is vomiting or
refuses to eat, (s)he needs to be taken to an emergency room for IV administration of
10% dextrose. The parents usually have an emergency protocol with them, which
contains basic information about the disorder, necessary diagnostic investigations and
guidelines for treatment.

Monitoring
Clinical observation is the most important tool for monitoring patients with VLCADD. They
should be observed for lethargy, recurrent vomiting, refusal to eat, tachypnea or apnea.
In these situations immediate evaluation in the ER is necessary. In situations of metabolic
decompensation hypoglycemia with little or no urinary ketones can develop, but a
normal blood glucose level does not rule out metabolic instability and should never be a
reason to delay therapy.
Cardiac evaluation
Any child diagnosed with VLCADD should be evaluated by a pediatric cardiologist for the
presence of cardiomyopathy upon diagnosis, followed by, at least, yearly evaluations.
Clinical symptoms suggesting cardiomyopathy are tachypnea, hepatomegaly,
tachycardia, feeding problems and exercise intolerance, but cardiomyopathy can be
present without any clinical symptoms.

Infections/Immunizations
Any infection can potentially lead to metabolic decompensation. Therefore its prevention
and/or early intervention is of particular importance. For this and other reasons
immunizations must be kept on track. This includes a yearly vaccine for influenza for
all children with VLCADD. There is no contraindication to any immunization because of
VLCADD, but patients and physicians should be alerted to the need for immediate
evaluation if high fever, lethargy or vomiting occurs in the first 24h. After an immunization
without any other clinical symptoms, administration of acetaminophen or ibuprofen is
warranted.

Surgical/surgical procedures
Infants and children with VLCADD can undergo necessary surgical/surgical procedures.
However, since any surgical procedure constitutes a potentially catabolic situation,
special management is necessary. Any surgery should include hospitalization
pre- and postoperatively. Preoperative fasting should be avoided with 10% dextrose
being started preoperatively and continuing postoperatively until the child is
eating/drinking well. If complicated surgery, or a postoperative period as an inpatient is
required, this should be carried out at a hospital with a metabolic service.

Growth and development
As in any child on a special dietary regime, close monitoring of all growth parameters
becomes particularly important. In cases with neurological deficits the child should be
integrated into an early intervention program. It is hoped that pre-symptomatic
identification and treatment of patients with SCADD will prevent any long-term
neurological problems.

Figure