Generic selectors
Exact matches only
Search in title
Search in content
Search in posts
Search in pages
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Special Article
Specialty Interface
Studies
Study Letter
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Reviews and Meta-analysis
Tables
Technology
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
View Point
Viewpoint
What’s new in Dermatology
View/Download PDF

Translate this page into:

Case Report
2006:72:5;364-366
doi: 10.4103/0378-6323.27754
PMID: 17050932

Cerebrotendinous xanthomatosis: Need for early diagnosis

K Muhammed, G Nandakumar, S Saritha
 Department of Dermatology and Venereology, Government Medical College, Kozhikode - 673 008, Kerala, India

Correspondence Address:
K Muhammed
Kunnummal House, Koroth School Road, Vatakara - 673101, Kozhikode, Kerala
India
How to cite this article:
Muhammed K, Nandakumar G, Saritha S. Cerebrotendinous xanthomatosis: Need for early diagnosis. Indian J Dermatol Venereol Leprol 2006;72:364-366
Copyright: (C)2006 Indian Journal of Dermatology, Venereology, and Leprology

Abstract

Cerebrotendinous xanthomatosis is a rare autosomal recessive lipid storage disease characterized by widespread tissue deposition of two neutral sterols, cholestanol and cholesterol, resulting in tendinous xanthomas, juvenile cataracts, progressive neurological defects and premature death from arteriosclerosis. The primary biochemical defect is deficiency of hepatic mitochondrial enzyme sterol-27-hydroxylase which catalyses the hydroxylation of cholestanol (5-alpha dehydro derivative of cholesterol) and this deficiency decreases bile acid synthesis. Substantial elevation of serum cholestanol and urinary bile alcohols with low to normal plasma cholesterol concentration establishes the diagnosis. Cerebrotendinous xanthomatosis is exceptionally rare in the Indian population. We are reporting a woman with this rare disorder, who was on antiepileptic and antipsychotic drugs for a prolonged period and whose original condition went undiagnosed. She presented with xanthomas on the Achilles tendons and the upper end of tibia. She was mentally subnormal and her serum cholestanol level was raised. Her younger sister too was severely affected by this disorder. Early treatment with chenodeoxycholic acid is known to prevent disease progression.
Keywords: Cerebrotendinous, Cholestanol lipidosis, Xanthomatosis
MRI scan showing severe cerebellar atrophy
MRI scan showing severe cerebellar atrophy
Tendinous xanthomas on both Achilles tendons
Tendinous xanthomas on both Achilles tendons

Introduction

Cerebrotendinous xanthomatosis (CTX) or cholestanol lipidosis is a rare autosomal recessive metabolic disease.[1],[2] A review of the literature revealed 175 patients with documented CTX of which 56% were females.[3] Several genetic studies have shown mutations in the sterol 27-hydroxylase gene (CYP 27 gene) resulting in markedly diminished activity of the enzyme sterol 27-hydroxylase in CTX patients.[3],[4] Sterol 27-hydroxylase enzyme catalyses the hydroxylation of cholestanol and its deficiency leads to elevated plasma cholestanol levels and consequently its accumulation in the brain, lens, tendons and other tissues.[1],[3],[4]

Diagnosis is confirmed by elevated plasma and bile cholestanol[1] and increased levels of urinary bile alcohols.[5] Treatment of choice is chenodeoxycholic acid.[1],[4] Cerebrotendinous xanthomatosis is exceptionally rare in the Indian population. Most cases have been reported in journals on neurology or metabolism with only four cases reported in dermatology literature.[5] We are reporting a case of CTX in a family of consanguineous parentage, with severer involvement of the younger sister.

Case report

A 26-year-old mentally retarded woman attended our outpatient department with complaints of swellings along the course of both Achilles tendons of 16 years duration [Figure - 1] and at the upper end of left tibia of three years duration. They were asymptomatic and gradually increasing in size. The patient gave history of surgery for bilateral mature cataract at the age of eight years. She developed hyperirritable behavior and poor scholastic performance so that she stopped going to school from fourth standard. She had gait ataxia with positive Rhomberg′s sign. She had generalized xerosis of the skin and asteatotic eczema of legs.

The patient was the eldest of four siblings of consanguineous parentage. Her 24-year-old younger sister had history of seizures since the first month of life and had bilateral mature cataract from an early age. She also had a gradual decline of mental function, being bedridden at the present and seemed more severely affected than the index case. She had developed Achilles tendon swellings three years ago. Her 20-year-old brother was on phenytoin sodium for grand mal seizures for the past three years while another 18-year-old brother was clinically unaffected.

The Achilles tendon swellings of both women and the swelling on the left tibial tuberosity of the index case were proved by biopsy to be tendinous xanthomas. Magnetic resonance imaging (MRI) of the index patient′s brain revealed severe cerebellar atrophy [Figure - 2], abnormal signals in the dentate nuclei and cerebellar white matter (hyperintense lesion in the T2 weighted images) with mild cerebral atrophy. A peripheral rim of marked hypointensity was seen around the hyperintense areas caused by xanthomas. Serum cholestanol of the patient (by partition chromatography and spectral photometric analysis) was elevated (3.8 ng/dl) which confirmed the diagnosis of cerebrotendinous xanthomatosis. Serum cholestanol of her epileptic brother was within normal limits (normal < 1 ng/dl).

Discussion

Cerebrotendinous xanthomatosis is a rare familial sterol storage disease.[1],[3] The primary biochemical defect is deficiency of hepatic mitochondrial enzyme sterol-27-hydroxylase which catalyses the hydroxylation of cholestanol (5-alpha dehydro derivative of cholesterol) and its deficiency decreases bile acid synthesis. This reduces feedback inhibition on cholesterol 7-alpha hydroxylase, which is the rate-limiting enzyme, resulting in synthesis and accumulation of more cholestanol.[4] Of the 175 documented cases of CTX, 71% had tendon xanthomas, 81% had low intelligence and incidence of cataracts and other neurological symptoms were seen in 92% and 100% cases respectively.[3] Patients usually present in childhood or early adult life.[1]

Tendon xanthomas, especially over the Achilles tendon are characteristic of the disorder and clinically resemble those seen in familial hypercholesterolemia or hyperlipoproteinemia but biochemical analysis reveals that they contain high amounts of cholestanol and little cholesterol. Mental retardation and progressive spasticity may develop.[1],[2]

Other reported manifestations of this rare syndrome include juvenile cataract,[1],[4],[6] abnormal behavior [2] and premature arteriovascular disease.[1],[7] In our case two of the four siblings had features of CTX. Both had tendon xanthomas, juvenile cataract, behavior abnormalities and progressive neurological problems mainly of cerebellar origin. As in our case, psychiatric manifestations may occur in patients with CTX.[2] These include depressed mood, irritability, poor appetite, insomnia, fatigability and pessimistic thinking.[2] These manifestations should be treated with antipsychotic drugs along with specific treatment.[2]

The diagnosis of CTX can be made biochemically by detecting increased serum levels of cholestanol[1] or urine bile alcohol[5] and genetically by detecting molecular defects in sterol-27-hydroxylase gene.[5] Conventional MRI studies have shown focal/ diffuse white matter abnormalities and different degrees of cerebral and cerebellar atrophy in the brain of patients with CTX. The bilateral nonhomogenous, hyperintense magnetic resonance signal in dentate nuclei and surrounding cerebellar white matter, can be considered as a neuroradiological feature suggestive of CTX and could become an important diagnostic marker.[8] The demyelinated areas appear hyperintense and the peripheral rim of marked hypointensity is caused by the xanthoma.[8]

CTX is very rare in the Indian population. In1999, Gobinda et al . reported CTX in two siblings from an Indian family and Gaikwad et al . described neuroimaging findings in two siblings from India.[8]

Several modes of treatment have been tried for CTX. Since 1975, chenodeoxy cholic acid (CDCA) 750 mg daily has been commonly used as the standard therapy, which influences the negative feedback of cholesterol and bile acid synthesis. There is a considerable decrease in the serum cholestanol and a sharp decline in the excretion of urine bile alcohols.[5] But a combination of CDCA with 3-hydroxy 3-methyl glutaryl coenzyme A (HMG COA) reductase inhibitors such as pravastatin or simvastatin (10-40 mg daily) is found to be more effective in lowering the serum cholestanol levels.[1] Long-term treatment may arrest or even reverse the progression of the disease.

Unfortunately, as in our case, the disease is not usually diagnosed before the second or third decade of life and at this stage cholestanol has already been extensively deposited in many tissues. Therefore, early diagnosis of this rare metabolic disease is necessary and CTX should be considered in every patient with intellectual impairment, spastic - ataxic signs, juvenile cataract and tendon xanthomas and MRI imaging should be done as soon as possible.

References
1.
Black MM, Gawkrodger DJ, Seymour CA, Weismann K. Metabolic and nutritional disorders. In : Rook, Wilkinson, Ebling, editors. Text book of Dermatology. 6th ed. Blackwell Science: London; 1998. p. 2577-677.
[Google Scholar]
2.
Lee Y, Lin PY, Chin NM, Chang WN, Wen JK. Cerebrotendinous Xanthomatosis with psychiatric disorders: Report of three siblings and literature review. Chang Gung Med J 2002;25: 334-40.
[Google Scholar]
3.
Moghadasian MH. Cerebrotendinous xanthomatosis: Clinical course, genotype and metabolic backgrounds. Clin Invest Med 2004;27:42-50.
[Google Scholar]
4.
Seyama Y. Cholesterol metabolism, molecular pathology and nutritional implications. J Med Food 2003;6:217-24.
[Google Scholar]
5.
Bel S, Garcia-Patos V, Rodriguez L, Selvan A, Diaz P, Wolthers BG, et al . Cerebrotendinous xanthomatosis. J Am Acad Dermatol 2001;45:292-5.
[Google Scholar]
6.
Campdelacreu J, Munoz E, Cervera A, Jauma S, Giros M, Tolosa E. Cerebrotendinous xanthomatosis without tendinous xanthomas: Presentation of two cases. Neurologia 2002;17: 647-50.
[Google Scholar]
7.
Valdivielso P, Calandra S, Durcan JC, Garuti R, Herrera E, Gonzalez P. Coronary heart disease in a patient with cerebrotendinous xanthomatosis. J Intern Med 2004:255:680-3.
[Google Scholar]
8.
Gaikwad SB, Garg A, Mishra NK, Gupta V, Srivastava A, Sarkar C. Cerebrotendinous xanthomatosis: Neuroimaging findings in two siblings from an Indian family. Neurol India 2003;51:401-3.
[Google Scholar]

Fulltext Views
219

PDF downloads
110
Show Sections