X-linked adrenoleukodystrophy: clinical, biochemical and pathogenetic aspects.

Abstract

X-linked adrenoleukodystrophy (X-ALD) is a clinically heterogeneous disorder ranging from the severe childhood cerebral form to asymptomatic persons. The overall incidence is 1:16,800 including hemizygotes as well as heterozygotes. The principal molecular defect is due to inborn mutations in the ABCD1 gene encoding the adrenoleukodystrophy protein (ALDP), a transporter in the peroxisome membrane. ALDP is involved in the transport of substrates from the cytoplasm into the peroxisomal lumen. ALDP defects lead to characteristic accumulation of saturated very long-chain fatty acids, the diagnostic disease marker. The pathogenesis is unclear. Different molecular mechanisms seem to induce inflammatory demyelination, neurodegeneration and adrenocortical insufficiency involving the primary ABCD1 defect, environmental factors and modifier genes. Important information has been derived from the X-ALD mouse models; species differences however complicate the interpretation of results. So far, bone marrow transplantation is the only effective long-term treatment for childhood cerebral X-ALD, however, only when performed at an early-stage of disease. Urgently needed novel therapeutic strategies are under consideration ranging from dietary approaches to gene therapy.

• Authors: Johannes Berger, Jutta Gärtner
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1763 Issue 12 Pg. 1721-32 (Dec 2006) ISSN: 0006-3002 [Print] Netherlands
• PMID: 16949688 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• ABCD1 protein, human
• ATP Binding Cassette Transporter, Subfamily D, Member 1
• ATP-Binding Cassette Transporters
• Biomarkers
• Fatty Acids

Topics

• ATP Binding Cassette Transporter, Subfamily D, Member 1
• ATP-Binding Cassette Transporters (genetics, metabolism)
• Adrenal Glands (pathology)
• Adrenoleukodystrophy (genetics, pathology, therapy)
• Animals
• Biological Transport
• Biomarkers (metabolism)
• Bone Marrow Transplantation
• Child
• Fatty Acids (metabolism)
• Female
• Humans
• Male
• Mice
• Mice, Knockout
• Mutation
• Nerve Degeneration (pathology)
• Peroxisomes (metabolism, pathology)
• Testis (pathology)