Cerebrotendinous xanthomatosis revisited

2021 ◽  
pp. practneurol-2020-002895
Author(s):  
Seyed Mohammad Baghbanian ◽  
Mohammad Reza Mahdavi Amiri ◽  
Hadi Majidi
Keyword(s):  
Autosomal Recessive ◽  
Lipid Storage ◽  
Cerebrotendinous Xanthomatosis ◽  
Progressive Ataxia ◽  
Progressive Neurodegeneration ◽  
Prompt Diagnosis

Cerebrotendinous xanthomatosis is a rare autosomal recessive lipid storage syndrome defined clinically by the triad of progressive neurodegeneration, juvenile cataracts and tendon xanthomas in adults. It is treatable, and a prompt diagnosis can improve outcomes. We describe a patient with this condition who presented with progressive ataxia.

Bilateral Achilles Tendon Xanthomas in a Patient with Cerebrotendinous Xanthomatosis

2017 ◽  
Vol 107 (1) ◽  
pp. 85-89 ◽  
Author(s):  
Mustafa Karakaplan ◽  
Emre Ergen ◽  
Gökay Görmeli ◽  
Mehmet Fatih Korkmaz ◽  
Nurzat Elmalı
Keyword(s):  
Achilles Tendon ◽  
Female Patient ◽  
Autosomal Recessive ◽  
Storage Disease ◽  
Lipid Storage ◽  
Cerebrotendinous Xanthomatosis ◽  
Flexor Hallucis Longus ◽  
Lipid Storage Disease ◽  
Longus Tendon ◽  
Motion Function

Cerebrotendinous xanthomatosis is a rare, autosomal recessive, lipid storage disease with accumulation of cholestanol in most tissues, particularly in the Achilles tendons. We described a 23-year-old female patient who had progressive painfull swelling of both Achilles tendons due to cerebrotendinous xanthomatosis. We performed surgery on both-side Achilles tendon tumors. Wide degenerative areas of the tendons were resected, and the flexor hallucis longus tendon was harvested and transferred to reconstruct motion function.

scholarly journals Cerebrotendinous Xanthomatosis: diversity of presentation and refining treatment with chenodeoxycholic acid

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Mahjabin Islam ◽  
Nigel Hoggard ◽  
Marios Hadjivassiliou
Keyword(s):  
Chenodeoxycholic Acid ◽  
Clinical Characteristics ◽  
Spastic Paraparesis ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Cerebrotendinous Xanthomatosis ◽  
Juvenile Onset ◽  
Progressive Ataxia ◽  
Classical Triad ◽  
High Index Of Suspicion

Abstract Background Cerebrotendinous xanthomatosis (CTX) is a rare but treatable neurometabolic disorder of lipid storage and bile acid synthesis. Whilst CTX is said to present with the classic triad of juvenile onset cataracts, tendon xanthomata and progressive ataxia, the diversity of presentation can be such that the diagnosis may be substantially delayed resulting in permanent neurological disability. Methods A retrospective review of the clinical characteristics and imaging findings of 4 patients with CTX presenting to the Sheffield Ataxia Centre over a period of 25 years. Results Although CTX-related symptoms were present from childhood, the median age at diagnosis was 39 years. Only 1 of the 4 cases had tendon xanthomata, only 2 cases had juvenile onset cataracts and 3 had progressive ataxia with one patient presenting with spastic paraparesis. Serum cholestanol was elevated in all 4 patients, proving to be a reliable diagnostic tool. In addition, cholestanol was raised in the CSF of 2 patients who underwent lumbar puncture. Despite treatment with chenodeoxycholic acid (CDCA) and normalization of serum cholestanol, CSF cholestanol remained high in one patient, necessitating increase in the dose of CDCA. Further adjustments to the dose of CDCA in the patient with raised CSF cholestanol resulted in slowing of progression. Two of the patients who have had the disease for the longest continued to progress, one subsequently dying from pneumonia. Conclusion A high index of suspicion for CTX, even in the absence of the classical triad is essential in reaching such diagnosis. The earlier the diagnosis and treatment, the better the outcome.

scholarly journals Future Prospects of Gene Therapy for Friedreich’s Ataxia

2021 ◽  
Vol 22 (4) ◽  
pp. 1815 ◽  
Author(s):  
Gabriel Ocana-Santero ◽  
Javier Díaz-Nido ◽  
Saúl Herranz-Martín
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Autosomal Recessive ◽  
State Of The Art ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
First Intron ◽  
Progressive Neurodegeneration ◽  
Feasible Solutions ◽  
Neurogenetic Disease

Friedreich’s ataxia is an autosomal recessive neurogenetic disease that is mainly associated with atrophy of the spinal cord and progressive neurodegeneration in the cerebellum. The disease is caused by a GAA-expansion in the first intron of the frataxin gene leading to a decreased level of frataxin protein, which results in mitochondrial dysfunction. Currently, there is no effective treatment to delay neurodegeneration in Friedreich’s ataxia. A plausible therapeutic approach is gene therapy. Indeed, Friedreich’s ataxia mouse models have been treated with viral vectors en-coding for either FXN or neurotrophins, such as brain-derived neurotrophic factor showing promising results. Thus, gene therapy is increasingly consolidating as one of the most promising therapies. However, several hurdles have to be overcome, including immunotoxicity and pheno-toxicity. We review the state of the art of gene therapy in Friedreich’s ataxia, addressing the main challenges and the most feasible solutions for them.

scholarly journals Current concepts in the treatment of hereditary ataxias

2016 ◽  
Vol 74 (3) ◽  
pp. 244-252 ◽  
Author(s):  
Pedro Braga Neto ◽  
José Luiz Pedroso ◽  
Sheng-Han Kuo ◽  
C. França Marcondes Junior ◽  
Hélio Afonso Ghizoni Teive ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Clinical Symptoms ◽  
Genetic Diagnosis ◽  
Symptomatic Treatment ◽  
Hereditary Ataxias ◽  
Disease Modifying Therapy ◽  
Progressive Ataxia ◽  
Cerebellar Ataxias ◽  
Disease Modifying

ABSTRACT Hereditary ataxias (HA) represents an extensive group of clinically and genetically heterogeneous neurodegenerative diseases, characterized by progressive ataxia combined with extra-cerebellar and multi-systemic involvements, including peripheral neuropathy, pyramidal signs, movement disorders, seizures, and cognitive dysfunction. There is no effective treatment for HA, and management remains supportive and symptomatic. In this review, we will focus on the symptomatic treatment of the main autosomal recessive ataxias, autosomal dominant ataxias, X-linked cerebellar ataxias and mitochondrial ataxias. We describe management for different clinical symptoms, mechanism-based approaches, rehabilitation therapy, disease modifying therapy, future clinical trials and perspectives, genetic counseling and preimplantation genetic diagnosis.

scholarly journals Case of Multiple Sulfatase Deficiency and Ocular Albinism: A Diagnostic Odyssey

2014 ◽  
Vol 41 (5) ◽  
pp. 626-631 ◽  
Author(s):  
Chitra Prasad ◽  
C. Anthony Rupar ◽  
Craig Campbell ◽  
Melanie Napier ◽  
David Ramsay ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Clinical Manifestations ◽  
Sensory Neuropathy ◽  
Compound Heterozygous ◽  
Ocular Albinism ◽  
Multiple Sulfatase Deficiency ◽  
Developmental Regression ◽  
Progressive Neurodegeneration ◽  
Severe Hypotonia ◽  
Work Up

AbstractBackgroundMultiple sulfatase deficiency (MSD) is a rare autosomal recessive inborn error of lysosomal metabolism. The clinical phenotypic spectrum encompasses overlapping features of variable severity and is suggestive of individual single sulfatase deficiencies (i.e., metachromatic leukodystrophy, mucopolysaccharidosis, and X-linked ichthyosis).Case ReportWe describe a 3-year-old male with severe hypotonia, developmental regression and progressive neurodegeneration, coarse facial features, nystagmus (from ocular albinism), and dysmyelinating motor sensory neuropathy. Ethics approval was obtained from the Western University Ontario.ResultsExtensive investigative work-up identified deficiencies of multiple sulfatases: heparan sulfate sulfamidase: 6.5 nmoles/mg/protein/17 hour (reference 25.0-75.0), iduronate-2-sulfate sulfatase: 9 nmol/mg/protein/4 hour (reference 31-110), and arylsulfatase A: 3.8 nmoles/hr/mg protein (reference 22-50). The identification of compound heterozygous pathogenic mutations in the SUMF1 gene c.836 C>T (p.A279V) and c.1045C>T (p.R349W) confirmed the diagnosis of MSD.ConclusionThe complex clinical manifestations of MSD and the unrelated coexistence of ocular albinism as in our case can delay diagnosis. Genetic counselling should be provided to all affected families.

Cerebrotendinous Xanthomatosis

2016 ◽  
Author(s):  
Aad Verrips
Keyword(s):  
Autosomal Recessive ◽  
Acid Metabolism ◽  
Cerebrotendinous Xanthomatosis ◽  
Bile Acid Metabolism ◽  
Hydroxylase Deficiency ◽  
Early Onset Dementia ◽  
Body Tissues ◽  
Neurological Features ◽  
Disease Stages ◽  
Rare Autosomal Recessive Disease

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disease due to a defect in bile acid metabolism. Worldwide, more than 300 patients have been described. Mutations in the CYP27A1 gene result in sterol 27-hydroxylase deficiency leading to the accumulation of cholestanol in multiple body tissues. Premature cataracts, chronic diarrhea, tendon xanthomas, and neurological deterioration are the predominant clinical features. There are several disease stages, from being nearly asymptomatic in the early childhood years to severe disability in later stages of life. Adult CTX patients are often misdiagnosed initially, especially when tendon xanthomasa are absent. CTX should be considered in all patients with premature cataracts and in patients with neurological features such as spasticity, early-onset dementia, ataxia, or Parkinsonism.

scholarly journals FRIEDREICH ATAXIA – A CASE REPORT

2014 ◽  
Vol 04 (02) ◽  
pp. 133-135
Author(s):  
Deepthi R. V. ◽  
Seema Pavanam ◽  
Vijaya Shenoy ◽  
Siddarth S. Joshi
Keyword(s):  
Autosomal Recessive ◽  
Trinucleotide Repeat ◽  
Friedreich Ataxia ◽  
Autosomal Recessive Disorder ◽  
Ataxic Gait ◽  
Progressive Ataxia ◽  
Extensor Plantar Response ◽  
Romberg Test ◽  
Endocrine Abnormality ◽  
Tendon Reflexes

Abstract:Friedreich ataxia is an autosomal recessive disorder, due to expansion of trinucleotide repeat in Frataxin gene which presents with ataxic gait, absent tendon reflexes, extensor plantar response and positive Romberg test. We present a child who came with complaints of progressive ataxia of gait since the age of 10 years and was diagnosed to have Friedreich ataxia. They have associated cardiomyopathy and endocrine abnormality like diabetes and hypothyroidism.

scholarly journals Cerebrotendinous xanthomatosis (a rare lipid storage disorder): a case report

2016 ◽  
Vol 10 (1) ◽  
Author(s):  
Syed Mohd Razi ◽  
Abhinav Kumar Gupta ◽  
Deepak Chand Gupta ◽  
Manish Gutch ◽  
Keshav Kumar Gupta ◽  
...  
Keyword(s):  
Case Report ◽  
Lipid Storage ◽  
Cerebrotendinous Xanthomatosis ◽  
Storage Disorder ◽  
Lipid Storage Disorder

A Novel ATM Gene Mutation Affecting Splicing in an Ataxia-Telangiectasia Patient

2021 ◽  
pp. 1-5
Author(s):  
Esra Arslan Ateş ◽  
Ayberk Türkyılmaz ◽  
Sevgi Bilgiç Eltan ◽  
Safa Barış ◽  
Ahmet Ilter Güney
Keyword(s):  
Ataxia Telangiectasia ◽  
Autosomal Recessive ◽  
Novel Mutation ◽  
Autosomal Recessive Disorder ◽  
Acceptor Site ◽  
Nonsense Mediated Decay ◽  
Splicing Pattern ◽  
Progressive Ataxia ◽  
Nucleotide Insertion ◽  
Alternatively Spliced

Ataxia-telangiectasia (AT) is an autosomal recessive disorder characterized by progressive ataxia, choreoathetosis and immunodeficiency beginning in early childhood. An 8-year-old girl was referred with a diagnosis of AT. She had gait disturbance and dysarthria for 3years. Multiple cutaneous telangiectases were observed on her face, trunk and limbs. Sequence analysis of the <i>ATM</i> gene revealed a homozygous c.7308–15A&#x3e;G mutation in IVS49. Human Splicing Finder predicted that the mutation could activate an intronic cryptic acceptor site. We designed primers for amplification of related exons (48–50) from cDNA for evaluating splicing pattern. Sequencing of <i>ATM</i> exons 48–50 revealed a 14-nucleotide insertion from intron 49, between exons 49 and 50, resulting in premature termination of translation at codon 2439. To conclude, we report a novel mutation in a classical AT case, which resulted in an alternatively spliced transcript and was predicted to form a truncated protein or null protein due to nonsense-mediated decay.

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