Adrenoleukodystrophy (ALD) is a degenerative disorder of the fatty white sheath covering nerve fibers, known as myelin. A type of leukodystrophy, the victims of ALD are typically male, as the disease is usually inherited in a sex-linked manner on the X chromosome. Leukodystrophies are disorders that affect the growth and/or development of myelin, a complex fatty neural tissue that insulates many nerves of the central and peripheral nervous systems. Without myelin, nerves are unable to conduct an impulse, leading to increasing disability as myelin destruction increases and intensifies. Leukodystrophies are different from demyelinating disorders such as multiple sclerosis, in which myelin is formed normally, but is lost by immunologic dysfunction or for other reasons. The following codes are used with International Statistical Classification of Diseases and Related Health Problems. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... An axon, or nerve fiber, is a long slender projection of a nerve cell, or neuron, which conducts electrical impulses away from the neurons cell body or soma. ... In neuroscience, myelin is an electrically insulating phospholipid layer that surrounds the axons of many neurons. ... Leukodystrophy refers to progressive degeneration of the white matter of the brain due to imperfect growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fiber. ... Sex-linked genes are those carried on the mammalian X chromosome but not the Y chromosome. ... The X chromosome is one of the two sex chromosomes in mammals (the other is the Y chromosome). ... A diagram showing the CNS: 1. ... The peripheral nervous system or PNS, is part of the nervous system, and consists of the nerves and neurons that reside or extend outside the central nervous system--to serve the limbs and organs, for example. ... A nerve is an enclosed, cable-like bundle of nerve fibers or axons, which includes the glia that ensheath the axons in myelin. ... t is the time duratio specific impulse [ ... To meet Wikipedias quality standards, this article or section may require cleanup. ...

Symptoms

The clinical presentation is largely dependent on the age of onset of the disease. The most severe type is the childhood cerebral form, which normally occurs in males between the ages of 5 and 10 and is characterized by failure to develop, seizures, ataxia, adrenal insufficiency and degeneration of visual and auditory function. This form can also occur in adolescents and, very rarely, adults. This article is about the medical term, epileptic seizure, as distinct from psychogenic non-epileptic seizure. ... Ataxia (from Greek ataxiā, meaning failure to put in order) is unsteady and clumsy motion of the limbs or trunk due to a failure of the gross coordination of muscle movements. ... In medicine, adrenal insufficiency (or hypocortisolism) is the inability of the adrenal gland to produce adequate amounts of cortisol in response to stress. ...

In another form of ALD, which primarily strikes young men, the spinal cord dysfunction is more prominent and therefore is called adrenomyeloneuropathy or "AMD." The patients usually present with weakness and numbness of the limbs and urination or defecation problems. Most victims of this form are also males, although some female carriers exhibit symptoms similar to AMD. Cross-section through cervical spinal cord. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... Anatomy of the anus and rectum Defecation or feceation, commonly referred to as pooping, shitting, or taking a shit, in physiology, is the act or process by which organisms eliminate solid or semisolid waste material from the digestive tract. ...

Adult and neonatal (which tend to affect both males and females and be inherited in an autosomal recessive manner) forms of the disease also exist but they are extremely rare. Some patients may present with sole findings of adrenal insufficiency (Addison's disease). In genetics, the term recessive gene refers to an allele that causes a phenotype (visible or detectable characteristic) that is only seen in a homozygous genotype (an organism that has two copies of the same allele). ... In medicine, adrenal insufficiency (or hypocortisolism) is the inability of the adrenal gland to produce adequate amounts of cortisol in response to stress. ...

Diagnosis

The diagnosis is established by clinical findings and the detection of serum long chain fatty acid levels. MRI examination reveals white matter abnormalities, and neuroimaging findings of this disease are quite reminiscent of the findings of multiple sclerosis. Genetic testing for the analysis of the defective gene is available in some centers. Blood plasma is a component of blood. ... The mri are a fictional alien species in the Faded Sun Trilogy of C.J. Cherryh. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ...

Pathophysiology

The most common form of ALD is X-linked (the defective gene is on the X chromosome, location Xq28), and is characterized by excessive accumulation of very long chain fatty acids (VLCFA) — fatty acids chains with 24–30 carbon atoms (particularly hexacosanoate, C26) in length (normally less than 20). This was originally described by Moser et al in 1981. So, when the ALD gene was discovered in 1993, it was a surprise that the corresponding protein was in fact a member of a family of transporter proteins, not an enzyme. It is still a mystery as to how the transporter affects the function the fatty acid enzyme and, for that matter, how high levels of very long chain fatty acids cause the loss of myelin on nerve fibers. Sex-linked genes are those carried on the mammalian X chromosome but not the Y chromosome. ... In chemistry, especially biochemistry, a fatty acid is a carboxylic acid (or organic acid), often with a long aliphatic tail (long chains), either saturated or unsaturated. ... General Name, Symbol, Number carbon, C, 6 Chemical series nonmetals Group, Period, Block 14, 2, p Appearance black (graphite) colorless (diamond) Atomic mass 12. ...

The gene (ABCD1 or "ATP-binding cassette, subfamily D, member 1") codes for a protein that transfers fatty acids into peroxisomes, the cellular organelles where the fatty acids undergo β-oxidation (Mosser et al 1993). A dysfunctional gene leads to the accumulation of long-chain fatty acids. Basic structure of a peroxisome Peroxisomes are ubiquitous organelles in eukaryotes that function to rid the cell of toxic substances. ... Schematic of typical animal cell, showing subcellular components. ... The most fundamental reactions in chemistry are the redox processes. ...

The precise mechanisms through which high VLCFA concentrations cause the disease are still (2005) unknown, but accumulation is severe in the organs affected. 2005 is a common year starting on Saturday of the Gregorian calendar. ...

The prevalence of X-linked adrenoleukodystrophy is approximately 1 in 20,000 individuals. This condition occurs with a similar frequency in all populations.

Treatment

While there is no cure for the disease, some dietary treatments, for example, Lorenzo's oil in combination with a diet low in VLCFA, have been used with limited success, especially before disease symptoms appear. A recent study by Moser et al (2005) shows positive long-term results with this approach. Lorenzos Oil is a 1992 dramatic film directed by George Miller. ...

Bone marrow transplantation has been proven to help ALD who are either presymptomatic or exhibiting mild symptoms early in the course of the disease. Bone marrow transplantation is not recommended for those suffering from AMD or very advanced onset ALD. Bone marrow transplantation is a medical procedure that involves stem cell transplantation. ...

Famous patients

Lorenzo Odone is probably the most famous patient with ALD. With the limited research available, his parents Augusto and Michaela Odone sparked the invention of Lorenzo's oil, which is the first agent to have shown therapeutic benefit in ALD. The quest for a treatment for Lorenzo was depicted in the film Lorenzo's Oil, and is the subject of the Phil Collins song Lorenzo (on his 1996 album Dance Into the Light). Lorenzo Odone (born May 29, 1978 [1]) is probably the most famous patient with Adrenoleukodystrophy (ALD). ... Michaela Murphy Odone was the mother of ALD patient Lorenzo Odone. ... Lorenzos Oil is a 1992 dramatic film directed by George Miller. ... Philip David Charles Collins (born January 30, 1951 in London), better known as Phil Collins, is a British rock/pop musician. ... Album cover for Phil Collinss Dance Into the Light. ...

References

• Moser HW, Moser AB, Frayer KK, Chen W, Schulman JD, O'Neill BP, Kishimoto Y. Adrenoleukodystrophy: increased plasma content of saturated very long chain fatty acids. Neurology 1981;31:1241-9. PMID 7202134.
• Mosser J, Douar AM, Sarde CO, Kioschis P, Feil R, Moser H, Poustka AM, Mandel JL, Aubourg P. Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters. Nature 1993;361:726-30. PMID 8441467.
• Moser HW, Raymond GV, Lu S-E, Muenz LR, Moser AB, Xu J, Jones RO, Loes DJ, Melhem ER, Dubey P, Bezman L, Brereton NH, Odone A. Follow-up of 89 asymptomatic patients with adrenoleukodystrophy treated with Lorenzo's Oil. Arch Neurol 2005;62;1073-80. PMID 16009761.

First title page, November 4, 1869 Nature is one of the oldest and most reputable scientific journals, first published on 4 November 1869. ...

External links

• OMIM 300100
• Adrenoleukodystrophy — NIH/NINDS
• Adrenoleukodystrophy — NIH/NCBI
• The role of peroxisomes in X-linked ALD
• ALDLife
• Adrenoleukodystrophy at National Center for Biotechnology Information
• The Myelin Project - Research Foundation organized by Augusto Odone, father of Lorenzo Odone