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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

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