3-methylglutaconic Aciduria with Cataracts, Neurologic Involvement and Neurtropenia

Background and History: 

This rare hereditary condition primarily affects the nervous system.

Clinical Correlations: 

Evidence of brain damage may be present at birth but there is much variation in the severity.  In fact some infants appear normal.  There is generally some evidence of delayed development in motor (movement) functions and in cognitive functioning.  Infants may be floppy in the neonatal period but often develop stiffness (spasticity) in their arms and legs later.  Some patients are unsteady (ataxic) on their feet and some have seizures.  Imaging of the brain reveals diffuse degeneration with loss of nerve cells and scarring.  Difficulty in swallowing is common.  The number of white cells is diminished and recurrent Infections may be a problem beginning in infancy.

A significant number of infants have cataracts which probably are congenital in origin.

The urine may contain increased amounts of a metabolic product called 3-methylglutaconic acid for which this disorder is named.

Genetics: 

Both members of a specific pair of genes when changed (mutated) are responsible for this disorder.  Both normal parents each contribute one of these mutated genes with a 50% probability and hence each of their children has a 25% chance of inheriting the mutated pair.

Diagnosis and Prognosis: 

The neurologic signs may provide a clue to this order during the neonatal period.  Pediatricians and pediatric neurologists as well as ophthalmologist may collaborate on the diagnosis and evaluation of these infants.

Infants with severe disease may succumb to this disorder in the first year of life.  However, others with milder disease may live for at least several decades.  There is no treatment for the general condition but physical therapy can delay some of the challenges.  Cataracts can, of course, be surgically removed but the indications vary widely and the decision to operate must be individualized to specific patients.

Additional Information
Inheritance/Pedigree: 
Autosomal recessive