Medium chain acyl-CoA Dehydrogenase Deficiency (MCADD)

Introduction
MCADD is an autosomal recessive disorder of fatty acid oxidation occurring in 1:10-
15,000 live births. MCADD results in an inability to break down fatty acids of medium
chain length for ketone and ATP synthesis (see figure).

Clinical Features
Affected individuals can be completely normal until prolonged fasting or infection leads to
metabolic decompensation. This typically presents with hypoketotic hypoglycemia,
seizures, vomiting, lethargy and coma. About 20% of infants with MCADD die during an
acute episode when the diagnosis is not yet suspected. Survivors may suffer from
neurological sequelae such as developmental delay, seizures, attention deficit hyperactive
disorder or other behavioral abnormalities.

Diagnosis
Newborn screen
Tandem mass spectrometry identifies elevations in medium chain acylcarnitines, most
notably octanoylcarnitinie (C8-carnitine)
Confirmation
*

Treatment
The basic treatment for MCADD is the avoidance of fasting. This involves regular feeding
during the day and limitation of overnight fasting. 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 food 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. Restriction of dietary fat is controversial but it is
reasonable during intercurrent infections. Carnitine administration may be provided in
the case of a low blood carnitine level.

Situations that risk metabolic decompensation
Children with MCADD are often clinically asymptomatic. Metabolic decompensation can
be triggered by the catabolic processes that occur in the course of an infection, after an
immunization or with a prolonged period of fasting. Lethargy, vomiting, apneas or
seizures are typical clinical features with or without hypoglycemia. 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 MCADD. They
should be observed for recurrent vomiting, refusal to eat, increased lethargy, apnea or
seizures. In these situations, immediate evaluation in the emergency room is necessary.
In situations of metabolic decompensation hypoglycemia can develop, but a normal
blood glucose does not rule out metabolic instability and should never be a reason to
delay therapy.

Infection/Immunization
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 MCADD. There is no contraindication to any immunization because of
MCADD, 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 MCADD can undergo necessary anesthetic/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 mentioned above, MCADD can cause failure to thrive. It is therefore crucial to closely
monitor all growth parameters on a regular basis. Moreover in cases with neurological
deficits. The child should be integrated into an early intervention program and
developmental progress closely monitored by both the metabolic team and the primary
care provider. It is hoped that pre-symptomatic identification and treatment of patients
with MCADD will prevent any long-term neurological problems.

Figure