Leukoencephalopathy With Predominant Infratentorial Involvement Caused by a Novel ABCD1 Mutation: Does the Spinocerebellar Variant of Adrenoleukodystrophy Exist?

Chiara Benzoni, Laura Farina, Viviana Pensato, Giorgio Marotta, Altin Kuqo, Elena Mauro, Davide Pareyson, Ettore Salsano

Research output: Contribution to journalArticle

Abstract

INTRODUCTION: X-linked adrenoleukodystrophy (X-ALD) encompasses several clinical and neuroimaging phenotypes, including cerebral X-ALD, the most common phenotype in children, and adrenomyeloneuropathy, the most common phenotype in adults. A spinocerebellar variant of X-ALD has been described in individuals from the Far East, but the criteria for its diagnosis are unclear. CASE REPORT: A 35-year-old man from Albania was assessed because of a familial, slowly progressive spastic-ataxic gait associated with neurogenic bladder, sexual dysfunctions, and manic-like behavior. There was no definite clinical feature that suggested cerebellar involvement (eg, cerebellar limb ataxia, nystagmus, and dysarthria). A few months earlier, he had received a diagnosis of Addison disease. Brain magnetic resonance imaging showed a leukoencephalopathy with predominant cerebellum and brainstem involvement, and FDG-PET revealed marked cerebellar hypometabolism. The diagnosis of X-ALD was made because we found an increase of very long chain fatty acids, and a new ABCD1 mutation (c.1627C>T, p.Pro543Ser). CONCLUSIONS: X-ALD should be included in the differential diagnosis of adult leukoencephalopathies with predominant involvement of infratentorial structures, that is, the cerebellum and brainstem. From a classification perspective, our patient (of white origin), like others (all of Asian origin), should be considered as suffering from a variant of adrenomyeloneuropathy rather than from spinocerebellar X-ALD. Actually, the term "spinocerebellar" or similar ones, such as "cerebello-brainstem dominant form," should be limited to those exceptional cases, in which both the clinical and neuroimaging findings point exclusively (or at least predominantly) to the involvement of infratentorial structures.

Original languageEnglish
Pages (from-to)194-197
Number of pages4
JournalThe neurologist
Volume24
Issue number6
DOIs
Publication statusPublished - Nov 1 2019

Fingerprint

Adrenoleukodystrophy
Leukoencephalopathies
Mutation
Brain Stem
Phenotype
Neuroimaging
Cerebellum
Albania
Neurologic Gait Disorders
Addison Disease
Dysarthria
Neurogenic Urinary Bladder
Cerebellar Ataxia
Far East
Ataxia
Differential Diagnosis
Fatty Acids
Magnetic Resonance Imaging

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

@article{5ec2108f18db48989f7928fe09b64c4e,
title = "Leukoencephalopathy With Predominant Infratentorial Involvement Caused by a Novel ABCD1 Mutation: Does the Spinocerebellar Variant of Adrenoleukodystrophy Exist?",
abstract = "INTRODUCTION: X-linked adrenoleukodystrophy (X-ALD) encompasses several clinical and neuroimaging phenotypes, including cerebral X-ALD, the most common phenotype in children, and adrenomyeloneuropathy, the most common phenotype in adults. A spinocerebellar variant of X-ALD has been described in individuals from the Far East, but the criteria for its diagnosis are unclear. CASE REPORT: A 35-year-old man from Albania was assessed because of a familial, slowly progressive spastic-ataxic gait associated with neurogenic bladder, sexual dysfunctions, and manic-like behavior. There was no definite clinical feature that suggested cerebellar involvement (eg, cerebellar limb ataxia, nystagmus, and dysarthria). A few months earlier, he had received a diagnosis of Addison disease. Brain magnetic resonance imaging showed a leukoencephalopathy with predominant cerebellum and brainstem involvement, and FDG-PET revealed marked cerebellar hypometabolism. The diagnosis of X-ALD was made because we found an increase of very long chain fatty acids, and a new ABCD1 mutation (c.1627C>T, p.Pro543Ser). CONCLUSIONS: X-ALD should be included in the differential diagnosis of adult leukoencephalopathies with predominant involvement of infratentorial structures, that is, the cerebellum and brainstem. From a classification perspective, our patient (of white origin), like others (all of Asian origin), should be considered as suffering from a variant of adrenomyeloneuropathy rather than from spinocerebellar X-ALD. Actually, the term {"}spinocerebellar{"} or similar ones, such as {"}cerebello-brainstem dominant form,{"} should be limited to those exceptional cases, in which both the clinical and neuroimaging findings point exclusively (or at least predominantly) to the involvement of infratentorial structures.",
author = "Chiara Benzoni and Laura Farina and Viviana Pensato and Giorgio Marotta and Altin Kuqo and Elena Mauro and Davide Pareyson and Ettore Salsano",
year = "2019",
month = "11",
day = "1",
doi = "10.1097/NRL.0000000000000252",
language = "English",
volume = "24",
pages = "194--197",
journal = "Neurologist",
issn = "1074-7931",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Leukoencephalopathy With Predominant Infratentorial Involvement Caused by a Novel ABCD1 Mutation

T2 - Does the Spinocerebellar Variant of Adrenoleukodystrophy Exist?

AU - Benzoni, Chiara

AU - Farina, Laura

AU - Pensato, Viviana

AU - Marotta, Giorgio

AU - Kuqo, Altin

AU - Mauro, Elena

AU - Pareyson, Davide

AU - Salsano, Ettore

PY - 2019/11/1

Y1 - 2019/11/1

N2 - INTRODUCTION: X-linked adrenoleukodystrophy (X-ALD) encompasses several clinical and neuroimaging phenotypes, including cerebral X-ALD, the most common phenotype in children, and adrenomyeloneuropathy, the most common phenotype in adults. A spinocerebellar variant of X-ALD has been described in individuals from the Far East, but the criteria for its diagnosis are unclear. CASE REPORT: A 35-year-old man from Albania was assessed because of a familial, slowly progressive spastic-ataxic gait associated with neurogenic bladder, sexual dysfunctions, and manic-like behavior. There was no definite clinical feature that suggested cerebellar involvement (eg, cerebellar limb ataxia, nystagmus, and dysarthria). A few months earlier, he had received a diagnosis of Addison disease. Brain magnetic resonance imaging showed a leukoencephalopathy with predominant cerebellum and brainstem involvement, and FDG-PET revealed marked cerebellar hypometabolism. The diagnosis of X-ALD was made because we found an increase of very long chain fatty acids, and a new ABCD1 mutation (c.1627C>T, p.Pro543Ser). CONCLUSIONS: X-ALD should be included in the differential diagnosis of adult leukoencephalopathies with predominant involvement of infratentorial structures, that is, the cerebellum and brainstem. From a classification perspective, our patient (of white origin), like others (all of Asian origin), should be considered as suffering from a variant of adrenomyeloneuropathy rather than from spinocerebellar X-ALD. Actually, the term "spinocerebellar" or similar ones, such as "cerebello-brainstem dominant form," should be limited to those exceptional cases, in which both the clinical and neuroimaging findings point exclusively (or at least predominantly) to the involvement of infratentorial structures.

AB - INTRODUCTION: X-linked adrenoleukodystrophy (X-ALD) encompasses several clinical and neuroimaging phenotypes, including cerebral X-ALD, the most common phenotype in children, and adrenomyeloneuropathy, the most common phenotype in adults. A spinocerebellar variant of X-ALD has been described in individuals from the Far East, but the criteria for its diagnosis are unclear. CASE REPORT: A 35-year-old man from Albania was assessed because of a familial, slowly progressive spastic-ataxic gait associated with neurogenic bladder, sexual dysfunctions, and manic-like behavior. There was no definite clinical feature that suggested cerebellar involvement (eg, cerebellar limb ataxia, nystagmus, and dysarthria). A few months earlier, he had received a diagnosis of Addison disease. Brain magnetic resonance imaging showed a leukoencephalopathy with predominant cerebellum and brainstem involvement, and FDG-PET revealed marked cerebellar hypometabolism. The diagnosis of X-ALD was made because we found an increase of very long chain fatty acids, and a new ABCD1 mutation (c.1627C>T, p.Pro543Ser). CONCLUSIONS: X-ALD should be included in the differential diagnosis of adult leukoencephalopathies with predominant involvement of infratentorial structures, that is, the cerebellum and brainstem. From a classification perspective, our patient (of white origin), like others (all of Asian origin), should be considered as suffering from a variant of adrenomyeloneuropathy rather than from spinocerebellar X-ALD. Actually, the term "spinocerebellar" or similar ones, such as "cerebello-brainstem dominant form," should be limited to those exceptional cases, in which both the clinical and neuroimaging findings point exclusively (or at least predominantly) to the involvement of infratentorial structures.

UR - http://www.scopus.com/inward/record.url?scp=85074545094&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85074545094&partnerID=8YFLogxK

U2 - 10.1097/NRL.0000000000000252

DO - 10.1097/NRL.0000000000000252

M3 - Article

C2 - 31688712

AN - SCOPUS:85074545094

VL - 24

SP - 194

EP - 197

JO - Neurologist

JF - Neurologist

SN - 1074-7931

IS - 6

ER -