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X-Linked Adrenoleukodystrophy: Addisonian Crisis in a Patient with Spastic Paraparesis-Ataxia Syndrome

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Movement Disorder Emergencies

Part of the book series: Current Clinical Neurology ((CCNEU))

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Abstract

X-linked adrenoleukodystrophy (ALD) is the most common inborn error of peroxisomal beta-oxidation, caused by pathogenic variants in the ABCD1 gene, affecting the functioning of a protein responsible for the transportation of very long-chain fatty acids (VLCFA) into the peroxisome. This defect results in the accumulation of VLCFA in different tissues, specially the central nervous system, suprarenal glands, and testis. There is no genotype-phenotype correlation, and affected families have a noticeable intrafamilial variability. Several different clinical presentations have been described for men with ALD, including a pre-symptomatic state, cerebral demyelinating ALD, adrenomyeloneuropathy (AMN), Addison’s disease, and a spinocerebellar subtype. The lifetime risk of Addison’s disease in ABCD1 carriers is about 80%. Virtually all men and up to 80% of heterozygous women develop AMN. Women present with milder and usually later-onset myelopathy than men. Neuroimaging carries diagnostic and prognostic implications. The diagnosis is based on the biochemical analysis of VLCFA plasma levels (although less sensitive in women), and/or genetic testing. A newborn ALD screening is now available. There is no cure, but early hematopoietic stem cell transplantation can arrest brain demyelination in appropriate candidates. Preventing Addisonian crisis is a mainstay in patient management, through corticosteroid replacement. Symptomatic treatment for AMN is primarily based on relieving spasticity and pain.

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  1. Department of Neuroscience, Clínica Dávila, Santiago, Chile

    Philippe A. Salles

  2. CETRAM, Santiago, Chile

    Philippe A. Salles

  3. Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA

    Philippe A. Salles & Hubert H. Fernandez

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    Steven J. Frucht

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A 28-year-old man with a 5-year history of progressive spastic paraparesis of unknown etiology, with comorbid sphincter and sexual dysfunction, was evaluated urgently because of a 3-day history of marked exacerbation of spasticity in his lower limbs, followed by two syncopal episodes, emesis, vegetative symptoms, and finally psychomotor agitation. At the ED he was noted to be agitated and confused. He had no fever, but his vital signs were remarkable for hypotension and tachycardia. Brain CT and CSF analysis were unremarkable. His clinical picture progressed with persistent hypotension, hypoglycemia, hyponatremia, hyperkalemia, and a low cortisol level. Suprarenal insufficiency was confirmed, and he was started on steroid replacement, along with correction of hypoglycemia and electrolyte imbalance. While his mentation slowly improved, his spasticity with severe spasms persisted. Neurological and general evaluation during admission was remarkable for hyperpigmented skin and gums, frontotemporal alopecia, cognitive slowness, spastic paraparesis-dystonic syndrome, and mild ataxia with hypermetric saccades, mild dysmetria, dysdiadochokinesia, and dyssynergia, with generalized hyperreflexia and bilateral Babinski signs. His MRI showed signal changes in parieto-occipital deep white matter and splenium of the corpus callosum. Based on the clinical and radiological characteristics, along with elevated very long chain fatty acids (VLCFA) levels, X-linked adrenoleukodystrophy was confirmed (MP4 77805 kb)

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Salles, P.A., Fernandez, H.H. (2022). X-Linked Adrenoleukodystrophy: Addisonian Crisis in a Patient with Spastic Paraparesis-Ataxia Syndrome. In: Frucht, S.J. (eds) Movement Disorder Emergencies. Current Clinical Neurology. Humana, Cham. https://doi.org/10.1007/978-3-030-75898-1_27

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