Glutaric acidemia I (GAI)

Introduction
GAI is an autosomal recessive disorder occurring in 1:30,000 caused by a deficiency in
the mitochondrial glutaryl-CoA dehydrogenase enzyme. Excess glutarylcarnitine leads to
carnitine deficiency, mitochondrial dysfunction. Hypoglycemia, metabolic acidosis and
a Reye like syndrome in addition to the specific motor dysfunctions, which can occur
during specific Glutaric acid metabolic crises.

Clinical Features
Neonatal
Macrocephaly, hypotonia
Infancy/childhood
Pathological rapid head growth
Hypotonia, irritability, feeding difficulties "jitteriness"
Consequences
Profound hypotonia, especially axial, lost motor skills, dystonic/choreoathetoid movement
disorder. NO loss of intellectual capacity.

Diagnosis
Newborn screen
Tandem mass spectrometry (detects elevated glutarylcarnitine)
Confirmation
Urinary organic acids
Serum carnitine (decreased and decreased free:total carnitine ratio)
Enzyme assay in cultured cells provides definitive diagnosis
Carrier testing remains equivocal.

Treatment
- Lysine restricted diet (very low protein +/- lysine free amino acid formula). Ensure
  plenty of fluids as ++sweating common.
- Oral carnitine and riboflavin
- Antispasmodics help reduce motor dysfunction but watch for worsening of truncal
  hypotonia. Avoid valproic acid if possible as competes for carnitine.
  Where feeding difficulties early gastrostomy very helpful in maintaining nutritional well-
  being.
- After 6 years of age can increase total protein load as risk of decompensation appears
  to be less.

Situations that risk metabolic decompensation
Fasting, intercurrent illness, post vaccination, surgery

Monitoring
Serum carnitine, for levels and ratio of free:total
Check for acute subdural hemorrhages following minor trauma

STAT emergency treatment
Including during infections ESPECIALLY if gastrointestinal. Supply frequent feeds with
NO protein and high carbohydrates. Consider early IV 10% glucose and IV carnitine.
Chlormethiazole may help severe hyperpyrexia.

Infection/Immunization
Intercurrent illnesses and vaccinations may aggravate hypotonia, unusual hand
movements and posturing but usually reversible and of little clinical significance though
may precipitate crises (usually after first birthday) 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 GA
type I. There is no contraindication to immunization because of GA type I, 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
* Pre-operative fasting can precipitate encephalopathic crises

Growth and development
Intellectually intact however capabilities dependant on avoidance of metabolic decompensation.

Figure