by Alexander Kurz
Adrenoleukodystrophy (ALD) is an X-chromosomal recessive disorder which leads to adrenal gland dysfunction. The disease is characterised by an abnormal storage of very long chain fatty acids (VLCFA) in myelin and in almost all cells of the body.
A variant of ALD is adrenomyeloneuropathy (AMN) in which the spinal cord and peripheral nerves are mainly affected, resulting in spastic paraparesis, sensory abnormalities in the legs, and bladder or anal sphincter dysfunction.
Symptoms and course
The adult variant of ALD becomes manifest at the age of 28 to 30 years. Clinical features include behavioural disorders, psychotic symptoms, impaired sexual function, ataxia, psudobulbar symptoms, progressive dyskinesia or polyneuropathy. Psychiatric and neurological symptoms are accompanied by adrenal gland dysfunction (fatigue, intermittend vomiting, arterial hypotension, hyperpigmentation of the skin) and hypogonadism.
Causes and risk factors
ALD is caused by mutations in the ABCD1 gene (Xq28), which encodes a transporter involved in the import of very long-chain fatty acids (VLCFA) into the peroxisome. The storage of abnormally long fatty acids alters the properties of myelin and results in a destabilisation of myelin membranes followed by demyelinisation.
The prevalence is estimated at 1:42.000 (Van Geel et al, 2001).
Juvenile, adolescent, and adult variants of ALD may be distinguished. The adult form of ALD accounts for approximately 3 % of all cases of ALD.
Cranial CT demonstrates demyelinisation in 80 % of ALD patients which is parieto-occipital initally and later also extends to frontal areas. MRT shows hyperintensities in the parieto-occipital white matter and in the spinal cord. The cerebrospinal fluid shows inflammation with pleocytosis, elevated protein content and intrathecal immunoglobulin production. As a consequence of demyelinisation, evoked potentials are slowed. Skin biopsy shows macrophages with typical inclusions. The diagnosis of ALD is established by the demonstration of elevated levels of VLCFA in plasma.
Care and treatment
Dietary restriction of VLCFA is not sufficient. Lorenzo’s oil is used to increase the intake of unsaturated fatty acits in order to inhibit the generation of VLCFA. Lorenzo’s oil, however, has no effect on demyelinisation and does not slow the progression of the disease. The combination of VLCFA-poor diet and Lorenzo’s oil normalises VLCFA in some patients and slows the progression of symptoms. Adverse effects include thrombopenia, lymphopenia, liver enzyme elevation, and reversible cardiomyopathy. Immune supressive therapy and high-dose intravenous immunoglobuline treatment had only minor effects. Recently bone marrow transplantation has been reported to improve neurological and neuropsychological symptoms if applied at the early stage of the disease.
United Leukodystrophy Foundation, 2304 Highland Drive Sycamore, Illinois USA 60178 http://www.ulf.org/
ALD Life, 209 High Street, Penge, London, SE20 7PF, www.aldlife.org
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- H. W. Moser: Adrenoleukodystrophy: phenotype, genetics, pathogenesis and therapy. Brain 120: 1485-1508, 1997
- H W Moser, A E Moser, I Singh, B P O’Neill: Adrenoleukodystrophy: Survey of 303 cases: Biochemistry, diagnosis, and therapy. An Neurol 16: 628-641, 1984
- B M van Geel, L Bezman, D J Loes, H W Moser, G V Raymond: Evolution of phenotypes in adult male patients with X-linked adrenoleukodystrophy. Ann Neurol 49: 186-194, 2001
- B M van Geel, J Assies, E B Haverkort, J H Koelman, B Verbeeten, R J Wanders, P G Barth: Progression of abnormalities in adrenomyeloneuropathy and neurologically asymptomatic X-linked adrenoleukodystrophy despite treatment with “Lorenzo’s oil”. J Neurol Neurosurg Psychiatry 67: 290-299, 1999
Last Updated: vendredi 17 août 2012