(X-linked adrenoleukodystrophy, Siemerling-Creutzfeldt disease, Schilder disease)

Estimated incidence: 1/17,000. Peroxysomial disease. X-linked or autosomal recessive transmission of a mutation of the ABCD1 gene (or ALDP) (Xq28). This leads to a deficiency of the peroxysomial beta-oxidation  of very long chain fatty acids with their accumulation (increased saturated cerotic acid level) in all tissues but especially the nervous system, the adrenal glands and testis. A neonatal screening by blood test can be done.  This is one of the clinical forms of leukodystrophies beside metachromatic leukodystrophy, Krabbe disease, Canavan disease, Alexander and Pelizaeus-Merzbacher disease. Adrenoleucodystrophy causes about 35 % of cases of all idiopathic Addison disease (see this term) in men .

There are 3 phenotypes: 

-         infantile cerebral form (40 % of cases): clinical signs appear between 4 and 8 years of age; progressive decrease in hearing, vision, cognitive, adrenal and motor functions, resulting in  total disability in less than two years;

-         adolescence or young adulthood form or adrenomyeloneuropathy (6 % of the cases): onset around 20 years of age  with signs of involvement of the anterior and posterior horns of the spinal cord: progressive paraparesis and sphincter disorders; in addition, a variable decrease in vision and hearing as well as signs of renal failure and hypogonadism; the disease gradually worsens over the years;

-         adrenomyeloneuropathy or Siemerling-Creutzfeldt disease (54 % of cases): adrenal failure (sometimes acute) appearing between 2 and 20 years  of age (7 years on average) without neurological signs at onset; a myeloneuropathy appears later, which is more severe  and more frequent among men than women (only 20 % of women show signs of myeloneuropathy, but not before the age of 35 years).

Treatment: diet poor in very long chain fatty acids. Bone marrow transplantation if the diagnosis is made early but results are disappointing.

Anesthetic implications: 

risk of aspiration and airway obstruction. Epilepsy. A so-called stress dose of hydrocortisone should be given at induction even in absence of clinical signs of adrenal insufficiency. Increased risk of propofol syndrome (PRIS) in case of continuous infusion of propofol ?

References : 

• Schwartz RE, Stayer SA, Pasquariello CA, Lowe DA, Foster CJ. 
  Anaesthesia for the patient with neonatal adrenoleukodystrophy. 
  Can J Anaesth 1994; 41:56-8.
• Tobias JD. 
  Anaesthetic considerations for the child with leukodystrophy. 
  Can J Anaesth 1992; 39:394-7. 
• Kindopp AS, Ashbury T.
  Anaesthetic management of an adult patient with X-linked adrenoleukodystrophy.
  Can J Anaesth 1998; 45: 990-2.
• Dubey P, Raymond GV, Moser AB, Kharkar S, Bezman L, Moser HW.
  Adrenal insufficiency in asymptomatic adrenoleukodystrophy patients identified by very long-chain fatty acid screening.
  J Pediatr 2005; 146: 528-32.
• Hamdiye CT, Yavuz G, Kamil T, Mine S. 
  Anesthesia management of a child with adrenoleukodystrophy. 
  Pediatr Anesth 2006; 16:221-2.
• Kuisle AM, Gauguet S, Karlin LI, Dauber A, McCann ME. 
  Postoperative adrenal crisis in an adolescent with Loeys-Dietz syndrome and undiagnosed adrenoleukodystrophy. 
  Can J Anesth 2001; 58: 392-5.
• Karaman Y, Goktay A, Agin H, Karaarslan U. 
  Propofol infusion syndrome or adrenoleukodystrophy? 
  Pediatr Anesth 2013; 23: 368-70.
• Tan SH, Ng VH. 
  Anaesthesia for a child with adrenoleukodystrophy :a case report and review of the literature. 
  Indian J Anaesth 2014; 58:63-5. 
• Kloesel B, Dua N, Eskuri R, Hall J, Cohen M, Rictsfeld M, Belani K.
  Anesthetic management of pediatric patients diagnosed with X-linked adrenoleukodystrophy : a single-center experience.
  Pediatr Anesth 2020 ; 30 : 124-36.

Updated February 2020