aciduria type I
Glutaric aciduria type I is
a rare disorder. It is produced by glutaryl-coenzyme A dehydrogenase deficiency.
The deficiency of this enzyme leads to an error in the catabolism of lysine,
hydroxylysine, and tryptophan. Glutaric acidemia type I has an autosomal
recessive inheritance. Megalencephaly is usually present from birth. Brain
CT scan and MRI are typical (Figure 288.1). Most neonates with glutaric
aciduria type I do not present in the neonatal period with any neurological
deficit. The neurological manifestations of glutaric acidemia type I consist
of an acute encephalitis-like illness characterized by somnolence, irritability,
and excessive sweating followed by slowly progressive signs of cerebral
deterioration. In some patients, these acute manifestations do not occur.
Instead, the disease starts as a slowly progressive central nervous system
deterioration. Urine organic acid chromatogram shows an increase in glutaric
acids and 3-hydroxyglutarate. The diagnosis is established by glutaryl-coenzyme
A dehydrogenase deficiency in leukocytes or fibroblasts.
Figure 288.1.— MRI of the brain reveal diffuse atrophy predominating
in the frontotemporal areas [A] with widening of the insular cisterns
[B] and bilateral necrosis of the of the caudate nuclei and the putamins
Canavan disease usually presents
with rapid head growth during the first weeks of life, marked hypotonia,
and nystagmus. The diagnosis is suspected by finding increased levels
of N-acetylaspartic acid in urine or an elevated N-acetyl aspartate (NAA)
peack by MRI spectroscopy of the brain, and is confirmed by demonstrating
decreased aspartoacylase activity in cultured fibroblasts.
Alexander disease may present
with macrocephaly in the neonatal period. The disease should be suspected
if MRI of the brain shows white matter disease with frontal predominance.
Brain biopsy shows fibrillary astrocytes with eosinophilic deposits (Rosenthal
common neonatal tumors are teratomas (Figure 288.2), astrocytomas, and
choroid plexus papilloma. Most neonatal brain tumors are midline and supratentorial.
Brain tumors may produce macrocephaly due to their large size or due to
hydrocephalus. Hydrocephalus may be noncommunicating due to obstruction
of cerebrospinal fluid flow inside the ventricular system, or communicating
due to excessive production of cerebrospinal fluid in choroid plexus papilloma.
In addition to macrocephaly, brain tumors in neonates may present with
lethargy, feeding difficulty, vomiting, bulging
anterior fontanelle, hemiparesis, and seizures. Seizures usually imply
that bleeding has occurred. Brain tumors are more frequent in neonates
with neurofibromatosis type I (optic gliomas), tuberous sclerosis (giant
cell astrocytoma), or with hepatic and renal tumors (primitive neuroectodermal
tumor) than in the general population. More
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MRI of the brain demonstrating a large teratoma. The tumor involves the
left optic nerve.