3-Methylcrotonyl-CoA Carboxylase Deficiency

Introduction
3-Methylcrotonyl-CoA Carboxylase (3-MCC) deficiency is an autosomal recessive
disorder of leucine catabolism (see figure). It produces an accumulation of
3- Methylcrotonyl-CoA. The clinical course in the untreated infant has been quite
variable.

Clinical Features
Neonatal
Diarrhea, Vomiting, Failure to thrive
Seizures have also been described
Infancy/childhood
Metabolic decompensation resembling Reye's syndrome
Failure to thrive
Developmental delay
Sudden death
Asymptomatic (diagnosed as a result of testing family members of an affected child)

Diagnosis
Newborn screen
Tandem mass spectrometry usually detects 3-MCC on the basis of elevations of
3-hydroxyisovalerylcarnitine (C5-OH-carnitine)
Confirmation

Treatment
Consists of avoidance of high protein foods and of supplementation with oral carnitine
(100mg/kg/d) usually divided in 3 daily doses. Carnitine forms, presumably, nontoxic
metabolites, which are excreted in the urine. The only side effects of carnitine include a
fishy odor and loosening of the stools.

Situations that risk metabolic decompensation
*

Monitoring & Emergency treatment
Ketonuria can be an early sign of metabolic decompensation and frequently precedes
clinical signs. Therefore patients should measure their urinary ketones on a daily basis.
Mild or moderate ketonuria indicates a catabolic situation and requires immediate
management in conjunction with a metabolic physician. The management generally
includes early aggressive treatment of infections, administration of fluids and calories,
mainly in the form of carbohydrates and fat, as well as assurance of adequate carnitine
administration. Parents usually have an emergency protocol with them that contains
basic information about the disorder as well as appropriate diagnostic evaluations and
emergency treatments.

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 3-MCC. There is no contraindication to immunization because of 3-MCC,
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 3-MCC can undergo necessary surgical/surgical procedures.
However, since any surgical procedure constitutes a potentially catabolic situation,
special management is necessary. 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, some children with 3-MCC deficiency have presented with failure to
thrive. It is therefore crucial to closely monitor all growth parameters on a regular basis.
During visits the metabolic center, dietary adjustments are usually made according to
growth measurements and other parameters. Developmental delay may also be a feature
of this disorder. Even with pre-symptomatic diagnosis and treatment, these children are
still at risk for neurological sequelae. If there are concerns about the neurological
development, 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.

Figure