Polyneuropathy with lipid deposits in Schwann cells and axonal degeneration in cerebrotendinous xanthomatosis

Voiculescu, Vlad Mihai; Alexianu, M; Popescu-Tismana, G.; Pastia, M.; Petrovici, A; A, Dan

doi:10.1016/0022-510x(87)90009-8

Cited by 14 publications

(6 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our study results are consistent with those of Verrips et al [15] in that axonal degeneration was concluded to be the predominant process of neuropathy in CTX, although in some of their patients, features of chronic demyelination and remyelination were also found [15]. In pathologic studies of peripheral nerves, Voiculescu et al [10], Donaghy et al [11] and Wang et al [17] found the deposition of lipid in Schwann cells in CTX patients with neuropathy, while this pathologic change was not noted in the studies of Katz et al [8], Argov et al [9] and Verrips A et al , [15]. Besides our four cases, another 12 CTX patients [15-17] with a peripheral neuropathy had a genetic analysis, but different mutation patterns were noted.…”

Section: Discussionsupporting

confidence: 92%

“…In the myopathologic study, mild neurogenic change was the main finding of our four CTX cases, and this denervation feature was also found in other related reports of CTX patients with peripheral neuropathy [7,10,15,18]. In the ultrastructual study of muscles, the main abnormal findings included changes of the mitochondria and membranous system, and an increased amount of lipid droplets, lipofuscin and glycogen (Table 3).…”

Section: Discussionsupporting

confidence: 85%

See 1 more Smart Citation

Neuromuscular abnormality and autonomic dysfunction in patients with cerebrotendinous xanthomatosis

et al. 2011

View full text Add to dashboard Cite

BackgroundCerebrotendinous xanthomatosis (CTX) is a rare lipid-storage disease. Neuromuscular abnormality and autonomic system (ANS) dysfuction in CTX are rarely examined in large-scale studies in the literature. We studied the peripheral nervous system, myopathology, and autonomic system of four CTX patients and performed a literature review of the reported CTX patients with peripheral neuropathy.MethodsFour biochemically and genetically confirmed CTX patients, belonging to two families, were included for study and all received nerve conduction study (NCS), muscle biopsy for histopathologic and ultrastructural study, skin biopsy for intraepidermal nerve fiber (INEF) density measurement, autonomic testings including sympathetic skin response, R-R interval variation and head-up tilt test using an automated tilt table to record the changes of blood pressure and heart rate in different postures. The Q-Sweat test was also applied for the detection of sweat amount and onset time of response. The clinical characteristics, study methods and results of 13 studies of peripheral neuropathy in CTX patients in the literature were also recorded for analysis.ResultsThe results of NCS study showed axonal sensory-motor polyneuropathy in three CTX cases and mixed axonal and demyelinating sensor-motor polyneuropathy in one. The myopathological and histopathologic studies revealed mild denervation characteristics, but the ultrastructural study revealed changes of mitochondria and the membranous system, and increased amounts of glycogen, lipofuscin and lipid deposition. The ANS study revealed different degrees of abnormalities in the applied tests and the INEF density measurement showed small fiber neuropathy in three of the four CTX patients. The literature review of peripheral neuropathy in CTX revealed different types of peripheral neuropathy, of which axonal peripheral neuropathy was the most common.ConclusionsPeripheral neuropathy, especially the subtype of axonal sensori-motor neuropathy, is common in patients with CTX. Evidence of lipid metabolic derangement in CTX can be reflected in ultrastructural studies of muscles. With an adequate multi-parametric evaluation, a high incidence of ANS abnormalities can be seen in this rare lipid-storage disease, and a high incidence of small fiber involvement is also reflected in the IENF density measurement of skin biopsies.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 85%

Neuromuscular abnormality and autonomic dysfunction in patients with cerebrotendinous xanthomatosis

et al. 2011

View full text Add to dashboard Cite

show abstract

“…5,6 We note large differences between previous reports of myelin and axonal damage in CTX. [11][12][13][14] Based on our observation and review of the other reports, the polyneuropathy in CTX can be classified into three pathological types: (i) axonal polyneuropathy, in which axonal degeneration and regeneration clusters of myelinated fibers are the main pathological changes; 8,[11][12][13][14] (ii) myelinated polyneuropathy, characterized by profuse demyelination, thin myelin sheaths and onion bulbs of myelinated fibers; 6,8,14 and (iii) mixed polyneuropathy, in which both axon and myelin are equally involved. The patient reported here belonged to the second type based on her electrophysiological and pathological changes.…”

Section: Discussionmentioning

confidence: 99%

Cerebrotendinous xanthomatosis with a compound heterozygote mutation and severe polyneuropathy

Wang¹,

Yuan²,

Zhang³

et al. 2007

Neuropathology

View full text Add to dashboard Cite

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessively inherited lipid storage disorder with multiple system involvement and has been reported worldwide. Here we report a Chinese family with CTX and present the pathological findings within peripheral nerves and CYP27A1 gene mutation analysis. We also review the published literature to discuss the clinical presentation and classification of neuropathy in this disease.

show abstract

“…Demyelination, gliosis, and involvement of the long tracts of the spinal cord have also been described [ 52 , 67 ]. Nerve biopsy reveals primary axonal degeneration, demyelination, and remyelination [ 40 , 68 - 70 ]. The pathological findings from needle aspiration and autopsy of the lungs of patients with CTX reveal granulomatous materials, foamy cells, and intracellular accumulations of foreign bodies [ 34 , 35 , 71 ].…”

Section: General Symptomsmentioning

confidence: 99%

Cerebrotendinous xanthomatosis: a comprehensive review of pathogenesis, clinical manifestations, diagnosis, and management

Nie

Chen

Cao

et al. 2014

Orphanet J Rare Dis

262

245

View full text Add to dashboard Cite

Cerebrotendinous xanthomatosis (CTX) OMIM#213700 is a rare autosomal-recessive lipid storage disease caused by mutations in the CYP27A1 gene; this gene codes for the mitochondrial enzyme sterol 27-hydroxylase, which is involved in bile acid synthesis. The CYP27A1 gene is located on chromosome 2q33-qter and contains nine exons. A CYP27A1 mutation leads to decreased synthesis of bile acid, excess production of cholestanol, and consequent accumulation of cholestanol in tissues. Currently there is no consensus on the prevalence of CTX, one estimate being <5/100,000 worldwide. The prevalence of CTX due to the CYP27A1 mutation R362C alone is approximately 1/50,000 in Caucasians. Patients with CTX have an average age of 35 years at the time of diagnosis and a diagnostic delay of 16 years. Clinical signs and symptoms include adult-onset progressive neurological dysfunction (i.e., ataxia, dystonia, dementia, epilepsy, psychiatric disorders,peripheral neuropathy, and myopathy) and premature non-neurologic manifestations (i.e., tendon xanthomas, childhood-onset cataracts, infantile-onset diarrhea, premature atherosclerosis, osteoporosis, and respiratory insufficiency). Juvenile cataracts, progressive neurologic dysfunction, and mild pulmonary insufficiency are unique symptoms that distinguish CTX from other lipid storage disorders including familial dysbetalipoproteinemia, homozygous familial hypercholesterolemia, and sitosterolemia, all of which might also present with xanthomas and cardiovascular diseases. Brain magnetic resonance imaging (MRI) shows bilateral lesions in the dentate nucleus of the cerebellum and mild white matter lesions. The classical symptoms and signs, namely elevated levels of cholestanol and bile alcohols in serum and urine, brain MRI, and the mutation in the CYP27A1 gene confirm the diagnosis of CTX. Early diagnosis and long-term treatment with chenodeoxycholic acid (750 mg/d) improve neurological symptoms and contribute to a better prognosis.

show abstract

Polyneuropathy with lipid deposits in Schwann cells and axonal degeneration in cerebrotendinous xanthomatosis

Cited by 14 publications

References 15 publications

Neuromuscular abnormality and autonomic dysfunction in patients with cerebrotendinous xanthomatosis

Neuromuscular abnormality and autonomic dysfunction in patients with cerebrotendinous xanthomatosis

Cerebrotendinous xanthomatosis with a compound heterozygote mutation and severe polyneuropathy

Cerebrotendinous xanthomatosis: a comprehensive review of pathogenesis, clinical manifestations, diagnosis, and management

Contact Info

Product

Resources

About