Short chain acyl CoA Dehydrogenase Deficiency

Introduction
Short chain acyl-CoA Dehydrogenase Deficiency (SCADD) is a rare autosomal recessive
disorder of fatty acid oxidation. Reported individuals have shown extremely variable phenotypes.

Clinical Features
Neonatal
Feeding difficulties
Hypertonia
Lethargy
Metabolic acidosis
Hypoglycemia
Sudden death
Infancy/childhood
Failure to thrive
Developmental delay
Seizures
Myopathy
Consequences

Diagnosis
Newborn screen Tandem mass spectrometry diagnosis on the basis of elevated short
chain acyl carnitines, notably C4-carnitine (butyrylcarnitine)
Confirmation
Plasma acylcarnitines (elevated butyryl-acylcarnitine)
Urinary acylglycines (elevated butyrylacylglycine)
Urinary organic acids (elevated ethylmalonic acid and other short chain acyl CoA
   metabolites)
Definitively by enzyme assay of cultured fibroblasts

Treatment
The basic treatment for SCADD 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. 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 SCADD).
However routinely treating with carnitine remains a topic of debate in the metabolic
community.

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, after an
immunization or with a prolonged period of fasting. Metabolic ketoacidosis and the
urinary excretion of the metabolites mentioned above are observed in these situations.
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 SCADD. They
should be observed for recurrent vomiting, refusal to eat, breathing abnormalities
(Kussmaul breathing secondary to metabolic acidosis), seizures or other neurological
abnormalities. Hypoglycemia or ketonuria may occur, but metabolic decompensation
may take place without these biochemical findings. Serum carnitine levels, if uncorrected
are often very low.

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 SCADD. There is no contraindication to any immunization because of
SCADD, 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 SCADD 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
SCADD can cause failure to thrive. Some patients are maintained on a low fat, high
carbohydrate diet. It is therefore crucial to closely monitor all growth parameters on a
regular basis. When fats are restricted, essential fatty acids need to be monitored. 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 SCADD will prevent any long-term neurological problems.

Figure