Epilepsy & Behavior 24 (2012) 380–381

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Epilepsy & Behavior

journal homepage: www.elsevier.com/locate/yebeh

Case Report

Early‐onset epilepsy as the main neurological manifestation of

cerebrotendinous xanthomatosis☆,☆☆
José Luiz Pedroso ⁎, Wladimir B. Pinto, Paulo V. Souza, Lucas T. Santos, Isabela C. Abud,
Marcela Amaral Avelino, Orlando G. Barsottini
Department of Neurology, Universidade Federal de São Paulo, São Paulo, Brazil

a r t i c l e i n f o a b s t r a c t

Article history: Cerebrotendinous xanthomatosis (CTX) is a rare inherited metabolic disorder, which usually presents with
Received 17 April 2012 diverse systemic manifestations (ophthalmologic, cardiac, and dermatologic symptoms), and neurological
Revised 23 April 2012 dysfunction, such as neuropsychiatric symptoms, cognitive decline, and ataxia. Epilepsy is rarely seen as
Accepted 24 April 2012
the main neurological manifestation of CTX. Herein, we describe a middle-aged woman with epilepsy since
Available online 30 May 2012
childhood as the only neurological symptom associated with the classical systemic manifestations of CTX.
Keywords:
© 2012 Elsevier Inc. All rights reserved.
Cerebrotendinous xanthomatosis
Epilepsy
Childhood

1. Introduction consultations. When she was twenty‐two, there was a progressive

Cerebrotendinous xanthomatosis (CTX) is an underdiagnosed rare
inborn metabolic disease, whose typical neurological features include
cerebellar ataxia, pyramidal signs, and neuropsychiatric symptoms.
Juvenile cataracts and variable degrees of chronic diarrhea and jaun-
dice are other systemic manifestations. Later in the disease, tendon
xanthomas appear [1]. Epilepsy is sometimes described in the syn-
drome, and it is hardly ever seen as the only and the first neurological
manifestation of CTX [2]. Herein, we describe a patient diagnosed with
CTX, whose main neurological feature was epilepsy since childhood.
2. Case report
A 35-year-old woman presented to our hospital with tonic-clonic
generalized seizures since childhood. Seizures started when she was
5 years old. At the onset, her parents reported two seizures per
week, and she received the most likely diagnosis of idiopathic epi-
lepsy. Her family history was unremarkable. In the following two
years, her seizures became more frequent, requiring hospitalizations.
There were two episodes of status epilepticus. Carbamazepine was
started in low doses (600 mg daily), with good control of seizures.
Bilateral cataracts were diagnosed when she was seven, in routine
☆ Financial disclosure: We have nothing to disclose.
☆☆ Ethical statement: Full consent was obtained from the patient for the case report
publication.
⁎ Corresponding author at: Rua Botucatu, 740, 04.023-900 São Paulo, SP, Brazil.
E-mail address: zeluizpedroso@yahoo.com.br (J.L. Pedroso).
increase of volume in the calcaneal and patellar regions, and tendon
xanthomas were identified in tibial tuberosities (Fig. 1). Her bilateral
Achilles tendon xanthomas were operated on when she was
23 years old. Neurological examination was normal. Brain magnetic
resonance imaging (MRI) disclosed mild white matter lesions
(Fig. 2). Several electroencephalograms (EEG) during asymptomatic
periods showed no epileptic discharges. General metabolic screening
and cholesterol profile were unremarkable, except for high serum
levels of cholestanol: 21.9 μg/mL (normal range of cholestanol:
lower than 4.2 μg/mL). There was also an association with high
levels of 7-dehydro-cholesterol, 8-dehydrocholesterol and 8(9)-cho-
lesterol. Idiopathic epilepsy was ruled out and CTX was diagnosed.
Chenodeoxycholic acid was unavailable.
3. Discussion
Cerebrotendinous xanthomatosis (OMIM 213700) represents an
autosomal recessive lipid storage disorder caused by different mu-
tations in CYP27A gene, located in 2q33-qter, which codes for he-
patic mitochondrial sterol 27-hydroxylase, involved in the normal
biosynthesis of bile acids, by promoting a hydroxylation at C27 of
5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol. It also occurs as
an upregulation of CYP7A, the gene encoding cholesterol 7-alpha-
hydroxylase [3,4]. There is a worldwide estimated prevalence of
1:70,000 in the general population. The major symptoms are pro-
duced by accumulation of cholestanol and cholesterol, particularly
in the nervous system, atherosclerotic plaques, and bone and ten-
don xanthomas [1].

1525-5050/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
doi:10.1016/j.yebeh.2012.04.121
 J.L. Pedroso et al. / Epilepsy & Behavior 24 (2012) 380–381
Fig. 1. Patient's knees showing tendon xanthomas.
Classic clinical features resemble progressive cerebellar ataxia as-
sociated with premature juvenile-onset cataracts (75% in the first de-
cade) and intractable chronic diarrhea, jaundice in infancy, and later,
with tendon xanthomas (prominently in the Achilles tendon, in tibial
tuberosity, in the triceps brachialis, and in the extensor tendons of the
fingers), osteoporosis, and myocardial infarction (10% of patients).
Tendon xanthomas typically develop after the second decade (70%
of the patients). Generally, systemic symptoms develop earlier than
neurologic signs [5]. Other neuropsychiatric manifestations other
than cerebellar ataxia include spastic paresis, frontal lobe dementia,
extrapyramidal symptoms, mental retardation, delusions, depression,
agitation, and hallucinations. Peripheral neuropathy and myelopathy
can also be seen [1,5]. Radiological assessment shows diffuse or
focal hypersignals in the white matter (typically infratentorial and
periventricular leukodystrophies), affecting the dentate nuclei and
Fig. 2. Axial FLAIR-weighted (A) and axial T2-weighted (B) brain MRIs disclosing mild white matter changes classically found in CTX patients.
381
cerebellar white matter in T2-weighted MRI scans associated with
diffuse cerebral atrophy, sometimes with the globus pallidus involve-
ment [6]. Laboratory studies show elevated plasma cholestanol levels
in gas chromatography or HPLC — a hallmark of the disease, with nor-
mal or decreased cholesterol levels. Cerebrotendinous xanthomatosis
treatment includes chenodeoxycholic acid and HMG-CoA-reductase
inhibitors [1].
Although epilepsy is seen in the early course of CTX and could be a
diagnostic cue, it is a rare initial symptom. Interestingly, epilepsy was
the first clinical manifestation and the only neurological symptom
in our patient. In CTX, EEG abnormalities are frequently observed,
and about 25% of patients have convulsive seizures [2]. Epilepsy,
although not classically described as a prominent cardinal feature, is
usually non-refractory and well-controlled with common antiepileptic
drugs. Epilepsy is also rarely described as an isolated neurological
feature in CTX. There is no specific type of epilepsy linked to CTX, and
there is no known genotypic to phenotypic correlation associated
with seizure development. However, the existence of chronic diarrhea,
juvenile cataracts, and cerebellar ataxia in a child or in an early-age
adult associated with epilepsy should call attention for the diagnosis
of CTX [2,7,8].
Early diagnosis of CTX is crucial, because early treatment with
CDCA leads to improvement or even prevention of CTX-associated
symptoms. Therefore, CTX should be considered as a differential diag-
nosis for patients with epilepsy with CTX-related manifestations [2].
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