Article

Cerebrotendinous xanthomatosis, a metabolic leukodystrophy with an
autosomal recessive inheritance, is secondary to deficiency of sterol
27-hydroxylase, an enzyme involved in cholesterol catabolism. Classical symptoms
include clinical or infraclinical xanthomas affecting the skin and tendons, early
cataracts, neurological signs and diarrhea. Brain imaging reveals involvement of
the dentate nuclei and periventricular white matter hyperintensities. The
diagnosis is based on an increased cholestanol level in serum, confirmed by the
presence of a mutation in the CYP27A1 gene. Treatment is based on
chenodeoxycholic acid. METHOD: We report a retrospective multicentric study of 15
cases of cerebrotendinous xanthomatosis diagnosed in French adults. Clinical,
molecular and MRI findings were recorded in all patients. RESULTS: The average
age at diagnosis was 39years (range 27-65). Disease onset occurred in childhood
in 73% of patients and in adulthood in 27%. All patients with a pediatric onset
were diagnosed during adulthood (age range 28-65years). Clinical symptoms
variably associated cerebellar syndrome, pyramidal syndrome, cognitive decline,
epilepsy, neuropathy (sought in 10 of our patients, present in forms in 8),
psychiatric disorders, cataract and xanthomas. One patient had an atypical
presentation: monoparesis associated with xanthomas. Brain MRI was abnormal in
all: findings consisted in T2-weighted hyperintensity of the dentate nuclei
(47%), periventricular leuoencephalopathy (73%) which preferentially involved the
posterior cerebral part (60%), leucoencephalopathy with a vascular pattern (7%),
hyperintensity of the cortico-spinal tracts (53%), globi pallidi, corpus callosum
and cerebral atrophy (33%). Serum cholestanol was elevated in 93% of patients.
The most frequent mutation was 1183C>T (n=5/15). Under treatment with
chenodeoxycholic acid, eight patients improved initially, followed by
stabilization in five of them, and worsening in the others. Four patients died.
CONCLUSION: Patients with the xanthoma-neurological disorder association should
be tested for cerebrotendinous xanthomatosis. The disease often begins in
childhood with a diagnostic delay but also in adulthood. Involvement of the
dentate nuclei is specific but not sensitive and the supratentorial
leucoencephalopathy is not specific but with an antero-posterior gradient. A
vascular distribution and involvement of the corpus callosum are possible. Serum
cholestanol assay is very reliable: an elevated level provides the diagnosis,
which must nevertheless be confirmed by molecular biology.
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Langue : FRANCAIS