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Adrenoleukodystrophy
- Brian P. O’Neill, Hugo W. Moser
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- Journal:
- Canadian Journal of Neurological Sciences / Volume 9 / Issue 4 / November 1982
- Published online by Cambridge University Press:
- 18 September 2015, pp. 449-452
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Adrenoleukodystrophy (ALD) is an X-linked degenerative disease characterized by progressive demyelination and adrenal insufficiency. Several phenotypes are described. In post-mortem tissues there is an accumulation of saturated or mono-unsaturated very long chain fattyacids (VLCFA) in the cholesterol ester fraction of adrenal cortex and cerebral white matter. The accumulated fatty acids are unbranched with carbon chain length between 23 and 32 with most containing 25 or 26 carbons. Determination of VLCFA in readily accessible tissues such as skin fibroblasts and plasma allows for reliable detection of patients and carriers.
31 - Adrenoleukodystrophy
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- By Hugo W. Moser, Kennedy Krieger Institute, Baltimore, MD, USA, Bjorn M. van Geel, Kennedy Krieger Institute, Baltimore, MD, USA
- Edited by E. Steve Roach, Wake Forest University, North Carolina, Van S. Miller, University of Texas Southwestern Medical Center, Dallas
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- Book:
- Neurocutaneous Disorders
- Published online:
- 31 July 2009
- Print publication:
- 08 January 2004, pp 258-265
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Summary
Introduction
X-linked adrenoleukodystrophy (X-ALD) is a genetically determined peroxisomal disorder that affects mainly the white matter and axons of the nervous system, the adrenal cortex, and the testis, but also has cutaneous manifestations. Its incidence is about 1 in 17 000 (Bezman et al., 2001). The disorder was first described in 1923 as a disorder of children (Siemerling & Creutzfeldt, 1923), but in 1976 adult forms were also recognized which are now known to be as common as the childhood forms (Budka et al., 1976; Griffin et al., 1977). The principal biochemical abnormality of X-ALD is the accumulation of saturated very long chain fatty acids in tissues (Igarashi et al., 1976) and body fluids (Moser et al., 1999). The deficient gene (ABCD1) codes for a peroxisomal membrane protein that is a member of the ATP-binding cassette (ABC transporter superfamily) (Higgins, 1992). The gene is located at Xq28. X-ALD must be distinguished from the less frequent neonatal adrenoleukodystrophy (NALD), which has an autosomal recessive mode of inheritance and is a disorder in which the biogenesis of the peroxisome is defective (Kelley et al., 1986; Gould et al., 2001). This chapter will deal only with X-ALD.
Clinical features
Neurologic findings
The clinical manifestations of X-ALD are summarized in several recent reviews (Moser et al., 2002; Moser 1997; Aubourg, 1996; van Geel et al., 1997). As seen in Tables 31.1(1) and (b), the range of clinical expression varies widely.
100 - Leukodystrophies
- from PART XIII - DISORDERS OF MYELIN
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- By Hugo W. Moser, Departments of Neurology and Pediatrics, Johns Hopkins University, Kennedy Krieger Institute, Baltimore, MD, USA, Kunihiko Suzuki, Neuroscience Center, University of North Carolina, USA
- Edited by Arthur K. Asbury, University of Pennsylvania School of Medicine, Guy M. McKhann, The Johns Hopkins University School of Medicine, W. Ian McDonald, University College London, Peter J. Goadsby, University College London, Justin C. McArthur, The Johns Hopkins University School of Medicine
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- Book:
- Diseases of the Nervous System
- Published online:
- 05 August 2016
- Print publication:
- 11 November 2002, pp 1633-1648
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Summary
The term leukodystrophy was first introduced by Bielschowsky and Henneberg (1928). In his review of the neuropathology of the leukodystrophies, James Powers et al. (2000) recommended that the term leukodystrophy should be applied only to ‘those progressive diseases of myelin in which a molecular abnormality is responsible for metabolic defects in myelin sheaths or myelin forming cells resulting in confluent destruction, or failed development, of central white matter’. Since the 1990s, remarkable progress has been achieved in the definition of the biochemical defect and the molecular basis of the leukodystrophies (Table 100.1).
In line with this recommendation, this chapter focuses on those genetic disorders in which central nervous system myelin is affected out of proportion to other elements of the nervous system, a judgement which may be somewhat arbitrary and subject to change as knowledge advances. Van der Knaap and Valk (1995) provide an excellent guide to the differential diagnosis of white matter abnormalities demonstrable on MRI and the acquired and genetically determined disorders of myelin that mimic the leukodystrophies. Experience in tertiary referral centres indicates that more than 50% of patients referred for ‘second opinion’ have leukoencephalopathies in which the cause cannot be determined utilizing diagnostic techniques that are currently available. The utilization of new neuroimaging techniques, such as magnetic resonance spectroscopy, combined with gene linkage analysis, has led to important recent advances and makes it likely that additional leukodystrophies will be defined in the near future (Alexander, 1949; Brenner et al., 2001; Verloes et al., 1997; van der Knaap et al., 1995, 1999; Topcu et al., 2000; Leegwater et al., 1999).
X-linked adrenoleukodystrophy
Background and general features
X-linked adrenoleukodystrophy (X-ALD) (Moser, 1997; Moser et al., 2000a,b) was described first in 1923. It was at first thought to be a variant of Schilder's disease ‘encephalitis periaxialis diffusa’ (Schilder, 1924), a disease category which has been analysed retrospectively and shown to be heterogeneous (Poser & van Bogaert, 1956). One of the three patients described by Schilder is now thought to have had X-ALD while the others had subacute sclerosing leukoencephalopathy and multiple sclerosis, respectively.