Spotlight on Adrenoleukodystrophy

In this article, Dr. Raphael Schiffmann, Director of the Institute of Metabolic Disease at Baylor Research Institute discusses X-linked adrenoleukodystrophy (X-ALD), the most common leukodystrophy, with an estimated incidence of 1:17,000. Both men and women may be affected. Plasma very long chain fatty acid (VLCFA) concentrations are already elevated at birth. VLCFA screening of at-risk relatives and of patients with idiopathic Addison disease permits diagnosis prior to neurologic involvement.

Three therapies are in current use: adrenal steroid replacement, preventive therapy with Lorenzo Oil for asymptomatic patients with normal MRI, and hematopoietic stem cell transplantation for patients with early cerebral involvement. The latter, however, does not correct the adrenal insufficiency or prevent the myelopathy. Ex-vivo lentiviral gene transfer to hematopoietic stem cells shows great promise. Newborn screening for this disorder has been developed and is beginning to be applied.

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Spotlight on Leukodystrophies

In this clinical summary, Dr. Raphael Schiffmann of the Institute of Metabolic Disease at Baylor Research Institute discusses leukodystrophies, a heterogeneous group of genetic disorders affecting the white matter of the central nervous system, sometimes with peripheral nervous system involvement. They are now most commonly grouped based on the initial pattern of central nervous system white matter abnormalities on neuroimaging. All leukodystrophies have MRI hyperintense white matter on T2-weighted images, whereas T1 signal may be variable. Mildly hypo-, iso- or hyperintense T1 signal relative to the cortex suggests a hypomyelinating patter. A significantly hypointense T1 signal is associated with a demyelinating form. Early diagnosis is important for genetic counseling and appropriate therapy where available.

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MedLink Neurology authors are always at work to bring you broad and up-to-date coverage of neurology topics. We are pleased to highlight clinical summaries that have been recently added or updated and to introduce the authors who write these authoritative articles. We hope you enjoy these overviews and appreciate the contributions of our more than 450 authors who keep MedLink Neurology the premier information resource for neurologists.

Spotlight on Alexander disease

In this clinical summary, Dr. Raphael Schiffmann of the Institute of Metabolic Disease at Baylor Research Institute discusses Alexander disease, a leukodystrophy that may occur at any age. Following the identification of mutations in the glial fibrillary acidic protein (GFAP) gene as the cause of Alexander disease, an increasing number of adult patients have been identified. The disease is caused by a combination of the formation of characteristic aggregates, called Rosenthal fibers, the sequestration of the protein chaperones alpha B-crystallin and HSP27 into Rosenthal fibers, and the activation of both Jnk and the stress response. The diagnosis is strongly suggested by MRI and confirmed by GFAP gene analysis. Cerebrospinal fluid GFAP levels are an important disease biomarker.

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MedLink Neurology authors are always at work to bring you broad and up-to-date coverage of neurology topics. We are pleased to highlight clinical summaries that have been recently added or updated and to introduce the authors who write these authoritative articles. We hope you enjoy these overviews and appreciate the contributions of our more than 450 authors who keep MedLink Neurology the premier information resource for neurologists.

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Spotlight on Globoid cell leukodystrophy

Globoid cell leukodystrophy, or Krabbe disease, is an autosomal recessive, rapidly progressive fatal disease when it occurs in infancy. The disease usually begins between the ages of 3 and 6 months with ambiguous symptoms, such as irritability or hypersensitivity to external stimuli, but soon progresses to severe mental and motor decline. Patients are initially hypertonic with hyperactive reflexes, but they later become flaccid and hypotonic. Blindness and deafness are common. Patients with late-onset forms, including adult onset, may present with blindness, spastic paraparesis, and dementia. Peripheral neuropathy presents in the infantile form but is variable in the later-onset forms. Brain MRI in infantile Krabbe disease is characteristic, including optic nerve enlargement and enhancement. Newborn screening is controversial, but presymptomatic hematopoietic stem cell transplantation can mitigate the disease.

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MedLink Neurology authors are always at work to bring you broad and up-to-date coverage of neurology topics. We are pleased to highlight clinical summaries that have been recently added or updated and to introduce the authors who write these authoritative articles. We hope you enjoy these overviews and appreciate the contributions of our more than 450 authors who keep MedLink Neurology the premier information resource for neurologists.