A disorder characterized by progressive
demyelinization of the central nervous system and peripheral adrenal
insufficiency resulting from adrenal gland atrophy.
Adrenomyeloneuropathy; Addison Disease and Cerebral
Sclerosis; Siemerling-Creutzfeldt Disease; Bronze Schilder Disease;
Genetic disorder, mainly affecting males but 50% of
female heterozygotes have symptoms.
1:15,000 to 1:100,000 in general population.
X-linked with six phenotypes, classified
according to age of onset, organ involvement, and neurological progression
rate. Most common form: X-adrenoleukodystrophy childhood form: (most severe);
second most common form: adrenomyeloneuropathy. Gene locus is the long arm
of X chromosome at position 28 (Xq28), which codes for an 80-kDa transmembrane
transporter protein. Mutation can be missense, frameshift, nonsense, or deletion.
This is distinct from neonatal adrenoleukodystrophy (autosomal recessive).
Very-long-chain fatty acids (VLCFA) are
metabolized by VLC acyl-CoA synthetases in peroxisomes or mitochondrion.
Adrenoleukodystrophy gene mutation may impair the peroxisomal import of this
synthetase, leading to VLCFAs (>C22) accumulation. It is uncertain whether
these long, rigid, acyl fatty acids reduce membrane fluidity, causing an
inflammatory response in the nervous system (demyelination), and reduce
steroid synthesis in the adrenal glands.
Clinical course with demyelinization signs and
association of peripheral adrenal insufficiency in 80% of children forms
and 65% of adult forms. Diagnosis is confirmed by abnormally high
saturated VLCFAs and C26:C22 ratio in blood or accessible tissues.
Radiologic imaging reveals symmetrical hypodense corpus callosum and
periventricular white matter. Prenatal (chorion villus biopsy) and female
heterozygotes (VLCFA profiles) diagnosis available.
X-adrenoleukodystrophy childhood form: normal childhood development until a mean age of
7 years, followed by parietal-occipital demyelination with rapidly
progressive dementia, behavioral changes, visual/auditory defect, and
seizures; 90% of patients have an adrenal insufficiency. Average life
span is 9.4 years. Adrenomyeloneuropathy: milder form with adult onset. Spinal cord involvement
(paraparesis/sphincter problems) is more common than cerebral (50% of
cases) or adrenal (30% of cases) dysfunction. Female heterozygotes: similar clinical picture
as adrenomyeloneuropathy; however, presenting normal adrenal glands (99% of
cases). Often misdiagnosed as multiple sclerosis.
Evaluate the neurological status for
evidence of cerebral and spinal demyelination (clinical, EEG, CT/MRI, nerves
velocity). Determine if adrenal dysfunction is present and adequately
treated. Blood examination: electrolytes, cell blood count, glucose, cortisol
N.B: Thrombocytopenia is often observed in patients treated with
Lorenzo's oil (40% of cases). As well, the use of this oil may cause
significant cardiac dysfunction.
Rapid sequence induction is indicated if
airway reflexes are impaired. The presence of dementia as a result of
neuronal demyelination may make the
patient sensitive to opioids. Regional anesthesia can be difficult (scoliosis) or
contraindicated (thrombocytopenia). Osteoporosis (hypogonadism) calls for
careful intraoperative positioning.
Succinylcholine should be avoided in
the presence of spinal cord compression or acute demyelination. Hypnomidate
should also be omitted (depresses adrenal function). Meperidine, ketamine,
sevoflurane and enflurane are relative contraindications if seizures are present.