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Paper 4
Published in Amanda Rabone, Benedict Thomson, Nicky Dineen, Vincent Helyar, Aidan Shaw, The Final FRCR, 2020
Amanda Rabone, Benedict Thomson, Nicky Dineen, Vincent Helyar, Aidan Shaw
X-linked adrenoleukodystrophy has a more posterior distribution of T2 hyperintensity with changes affecting the periventricular parieto-occipital white matter and splenium of the corpus callosum progressing to affect the visual and auditory pathways, with peripheral enhancement commonly seen.
DTI of Developmental and Pediatric Disorders
Published in Andrei I. Holodny, Functional Neuroimaging, 2019
Michael J. J. Kim, James M. Provenzale
X-linked adrenoleukodystrophy (ALD) is a peroxisomal disorder caused by a defect in ABCD1 gene, leading to the accumulation of saturated very long-chain fatty acids that affect the CNS, adrenal cortex, and testes (34–41). The brain lesions are typically characterized by symmetrical inflammatory demyelination in the cerebral and cerebellar white matter (35). The childhood cerebral form of ALD most commonly presents in boys four- to eight-years old. The initial clinical manifestations are often learning disabilities and behavioral problems, rapidly deteriorating to blindness, quadriparesis, and ultimately death within ten years of diagnosis (36). Bone marrow transplantation during a limited time window is generally considered the most effective treatment.
Test Paper 7
Published in Teck Yew Chin, Susan Cheng Shelmerdine, Akash Ganguly, Chinedum Anosike, Get Through, 2017
Teck Yew Chin, Susan Cheng Shelmerdine, Akash Ganguly, Chinedum Anosike
Dysmyelinating diseases, or leukodystrophies, encompass a wide spectrum of inherited neurodegenerative disorders affecting the integrity of myelin in the brain and peripheral nerves. Most of these disorders fall into one of three categories – lysosomal storage diseases, peroxisomal disorders and diseases caused by mitochondrial dysfunction – and each leukodystrophy has distinctive clinical, biochemical, pathological and radiological features. X-linked adrenoleukodystrophy is an inherited white matter disorder caused by gene mutation (ALD gene) resulting in abnormal formation of myelin. The childhood cerebral form (CCALD) is the most common and affects males aged between 4 and 10 years. Hyperpigmentation can occur as a result of adrenal insufficiency. The diagnostic clue is symmetric, peritrigonal white matter abnormality involving the splenium. Alexander disease characteristically involves the frontal white matter preferentially, and Canavan disease causes diffuse white matter abnormality.
Genetic diseases mimicking multiple sclerosis
Published in Postgraduate Medicine, 2021
Chueh Lin Hsu, Piotr Iwanowski, Chueh Hsuan Hsu, Wojciech Kozubski
X-linked adrenoleukodystrophy(X-ALD), a genetic disease that affects both the CNS and adrenal glands, is caused by a mutation in the ABCD1 gene, which encodes essential messages to make X-linked adrenoleukodystrophy protein (ALDP). The role of ALDP is to transport very- long -chain fatty acids (VLCFA) into peroxisomes for breaking down. Insufficient amounts of ALDP result in the building up of VLCFA which overwhelms and damages the adrenal cortex and normal myelin protection of the nerves. X-ALD affects males more than females, as suggested by its name. Three major patterns of X-ALD have been identified, namely a childhood cerebral form, an adrenomyeloneuropathy form, and an adrenal insufficiency-only form. Childhood cerebral form is considered a rapidly fatal disorder with the onset of neurologic symptoms to total disability or death within three years. Almost all male X-ALD patients at some points in their disease course would be affected by myelopathy and peripheral neuropathy, which are collectively named adrenomyeloneuropathy (AMN) [89,90]. In the male, the elevated level of VLCFA is highly sensitive to X-ALD and is thus favorable for diagnosis. However, in women, the genetic test for the ABCD1 gene is required because 15% of female carriers have normal plasma VLCFA levels [91].
Downregulation of inflammatory markers by conjugated linoleic acid isomers in human cultured astrocytes
Published in Nutritional Neuroscience, 2019
Francesca Saba, Annarita Sirigu, Rita Pillai, Paola Caria, Lina Cordeddu, Gianfranca Carta, Elisabetta Murru, Valeria Sogos, Sebastiano Banni
We previously demonstrated that feeding rats with high concentrations of CLA isomers resulted in their incorporation into the nervous tissue, indicating that these fatty acids are able to pass the BBB.15 Recently, it has been shown that feeding rats with a CLA-enriched diet induced an increased hippocampal phospholipase A2 (PLA2) activity, associated with memory improvement.38 Moreover, in X-linked adrenoleukodystrophy female carriers, we previously detected a significant increase in CLA in the CSF upon its intake, where it was associated with a decrease in inflammatory markers and an increase in the DHA/EPA ratio.16 The present study strongly suggests that astrocytes play a role in the anti-neuroinflammatory effects exerted by CLA isomers associated with changes in fatty acid metabolism.
An update on gene therapy for lysosomal storage disorders
Published in Expert Opinion on Biological Therapy, 2019
Murtaza S. Nagree, Simone Scalia, William M. McKillop, Jeffrey A. Medin
As correction of most LSDs appears to require systemic delivery of enzyme, autologous HSC-based gene therapy will be most effective for LSDs in which corrective enzyme can be secreted and subsequently taken up by affected ‘bystander’ cells. Conversely, the potential of HSC-directed gene therapy in a disorder without the ability to cross-correct can be seen in the recent success treating X-linked adrenoleukodystrophy, a non-LSD caused by ABCD1 gene dysfunction (NCT01896102) [41]. In that trial, hematopoietic-derived cells migrated into the CNS, persisted, and provided ‘factories’ of functional ABCD1, providing clinical benefit years following transplant [41].