Back سوء تغذية الكظرية وبيضاء الدماغ Arabic Adrenoleukodistrofija BS Adrenoleukodystrofi Danish Adrenoleukodystrophie German Αδρενολευκοδυστροφία Greek Adrenoleucodistrofia Spanish آدرنولکودیستروفی Persian Adrenoleukodystrofia Finnish Adrénoleucodystrophie liée à l'X French Adrenoleucodistrofia Galician
| Adrenoleukodystrophy | |
|---|---|
| Other names | X-linked adrenoleukodystrophy, ALD, X-ALD, Siemerling–Creutzfeldt disease, bronze Schilder disease |
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| White matter, with reduced volume and increased signal intensity. The anterior white matter is spared. Features are consistent with X-linked adrenoleukodystrophy. | |
| Pronunciation | |
| Specialty | Medical genetics |
| Types | X-Linked ALD |
Adrenoleukodystrophy (ALD) is a disease linked to the X chromosome. It is a result of fatty acid buildup caused by failure of peroxisomal fatty acid beta oxidation which results in the accumulation of very long chain fatty acids in tissues throughout the body. The most severely affected tissues are the myelin in the central nervous system, the adrenal cortex, and the Leydig cells in the testes. The long chain fatty acid buildup causes damage to the myelin sheath of the neurons of the brain, resulting in seizures and hyperactivity. Other symptoms include problems in speaking, listening, and understanding verbal instructions.
Clinically, ALD presents as a heterogeneous disorder, showing several distinct phenotypes, and no clear pattern of genotype–phenotype correlation. As an X-linked disorder, ALD presents more frequently and severely in males; however, approximately 80% of heterozygote females show some symptoms later in life.[1] Approximately one third of male ALD patients will present with the childhood cerebral form of the disease, which is the most severe form.[2] It is characterized by normal development in early childhood, followed by rapid degeneration to a vegetative state. The other forms of ALD vary in timing of onset and in clinical severity, ranging from adrenal insufficiency alone to progressive paraparesis in early adulthood.
ALD is caused by mutations in ABCD1, a gene located on the X chromosome that codes for ALD, a peroxisomal membrane transporter protein. The exact mechanism of the pathogenesis of the various forms of ALD is not known. Biochemically, individuals with ALD show very high levels of unbranched, saturated, very long chain fatty acids, particularly cerotic acid (26:0). The level of cerotic acid in plasma does not correlate with clinical presentation. Treatment options for ALD are limited. For the childhood cerebral form, stem cell transplant and gene therapy are options if the disease is detected early in the clinical course. Adrenal insufficiency in ALD patients can be successfully treated. ALD is the most common peroxisomal inborn error of metabolism, with a minimum estimated incidence of 1:42,000 for hemizygotes and 1:16,800 for hemizygotes and heterozygotes, though the incidence is likely to increase with improved newborn screening.[3] It does not have a significantly higher incidence in any specific ethnic group.
- ^ Huffnagel, Irene C.; Dijkgraaf, Marcel G. W.; Janssens, Georges E.; van Weeghel, Michel; van Geel, Björn M.; Poll-The, Bwee Tien; Kemp, Stephan; Engelen, Marc (2019-02-07). "Disease progression in women with X-linked adrenoleukodystrophy is slow". Orphanet Journal of Rare Diseases. 14 (1): 30. doi:10.1186/s13023-019-1008-6. ISSN 1750-1172. PMC 6367840. PMID 30732635.
- ^ Berger, Johannes; Gärtner, Jutta (December 2006). "X-linked adrenoleukodystrophy: Clinical, biochemical and pathogenetic aspects". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1763 (12): 1721–1732. doi:10.1016/j.bbamcr.2006.07.010. PMID 16949688.
- ^ Bezman, Lena; Moser, Ann B.; Raymond, Gerald V.; Rinaldo, Piero; Watkins, Paul A.; Smith, Kirby D.; Kass, Nancy E.; Moser, Hugo W. (2001). "Adrenoleukodystrophy: Incidence, new mutation rate, and results of extended family screening". Annals of Neurology. 49 (4): 512–517. doi:10.1002/ana.101. ISSN 1531-8249.