scholarly journals Clinical and genetic characteristics of Chinese patients with cerebrotendinous xanthomatosis

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Qing-Qing Tao ◽  
Yun Zhang ◽  
Hui-Xia Lin ◽  
Hai-Lin Dong ◽  
Wang Ni ◽  
...  
Keyword(s):  
Chinese Population ◽  
Autosomal Recessive ◽  
Storage Disease ◽  
Clinical Manifestations ◽  
Cerebrotendinous Xanthomatosis ◽  
Chinese Patients ◽  
Lipid Storage Disease ◽  
Genetic Characteristics ◽  
Pathogenic Mutations ◽  
Autosomal Recessive Pattern

Abstract Background Cerebrotendinous xanthomatosis (CTX) is a rare inborn lipid-storage disease caused by mutations in the sterol 27-hydroxylase (CYP27A1) gene with an autosomal recessive pattern of inheritance. To date, only 19 CTX patients from 16 families have been reported in the Chinese population. Results Three novel likely pathogenic mutations (c.368_374delCCAGTAC, c.389 T > A and c.571C > T) and 7 previously reported pathogenic mutations (c.379C > T, c.435G > T, c.1016C > T, c.1214G > A, c.1263 + 1G > A, c.1420C > T and c.1435C > T) were identified. In addition, we summarized the genotypes and phenotypes of reported Chinese CTX patients. The most predominant mutations in CYP27A1 were c.410G > A and c.379C > T, and the most common clinical manifestations were pyramidal signs, xanthomatosis, cerebellar ataxia, and cognitive impairment. Conclusion Our study broadens the genetic and clinical spectrum of CTX and provides insightful information to help better diagnose and understand the disease.

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 Optic Neuropathy with Features Suggestive of Optic Neuritis in Cerebrotendinous Xanthomatosis

2019 ◽  
Vol 2019 ◽  
pp. 1-4
Author(s):  
Miyuki Miyamoto ◽  
Nobuyuki Ishii ◽  
Hitoshi Mochizuki ◽  
Kazutaka Shiomi ◽  
Tomoko Kaida ◽  
...  
Keyword(s):  
Optic Neuritis ◽  
Optic Neuropathy ◽  
Storage Disease ◽  
Elevated Serum ◽  
Brain Magnetic Resonance Imaging ◽  
Cerebrotendinous Xanthomatosis ◽  
Gadolinium Enhancement ◽  
Lipid Storage Disease ◽  
Optic Disc Swelling ◽  
The Right

We describe our encounter with a 39-year-old man who exhibited acute painless visual loss and progressive gait disturbance. He had tendinous xanthoma and several neuroophthalmological findings indicative of optic neuropathy in the right eye, including afferent pupillary defect, cecocentral scotoma, and optic disc swelling. Neurological examination showed cerebellar ataxia and pyramidal weakness. Brain magnetic resonance imaging revealed bilateral swelling in the optic nerves with gadolinium-enhancement suggesting optic neuritis, an enlarged fourth ventricle, atrophy of the cerebellum, and hyperintensities in the bilateral dentate nuclei. The patient was diagnosed with cerebrotendinous xanthomatosis (CTX) based on an elevated serum cholestanol level and a homozygous missense mutation in CYP27A1. CTX is a genetic lipid storage disease caused by dysfunction of the mitochondrial enzyme sterol 27-hydroxylase. With respect to ophthalmological manifestations, juvenile cataracts and optic neuropathy are common findings in patients with CTX, but there have been no reports of optic neuropathy with features suggestive of optic neuritis. Thus, this case illustrates that clinicians should consider a diagnosis of CTX in patients with cardinal features of CTX even if the patients show signs indicative of optic neuritis.

scholarly journals Three Novel and One Potential Hotspot CPT1A Variants in Chinese Patients With Carnitine Palmitoyltransferase 1A Deficiency

2021 ◽  
Vol 9 ◽  
Author(s):  
Weifeng Zhang ◽  
Yanru Chen ◽  
Chunmei Lin ◽  
Weilin Peng ◽  
Qingliu Fu ◽  
...  
Keyword(s):  
Chinese Population ◽  
Clinical Symptoms ◽  
Allelic Frequency ◽  
Carnitine Palmitoyltransferase ◽  
Chinese Patients ◽  
Tandem Mass ◽  
Newly Diagnosed ◽  
Genetic Characteristics ◽  
Mitochondrial Fatty Acid ◽  
Novel Variants

Carnitine palmitoyltransferase 1A (CPT1A) deficiency is an inherited disorder of mitochondrial fatty acid β-oxidation that impairs fasting ketogenesis and gluconeogenesis in the liver. Few studies implementing newborn screening (NBS) for CPT1A deficiency in the Chinese population have been reported. This study aimed to determine the biochemical, clinical, and genetic characteristics of patients with CPT1A deficiency in China. A total of 204,777 newborns were screened using tandem mass spectrometry at Quanzhou Maternity and Children's Hospital between January 2017 and December 2018. Newborns with elevated C0 levels were recruited, and suspected patients were subjected to further genetic analysis. Additionally, all Chinese patients genetically diagnosed with CPT1A deficiency were reviewed and included in the study. Among the 204,777 screened newborns, two patients were diagnosed with CPT1A deficiency; thus, the estimated incidence in the selected population was 1:102,388. In addition to the two patients newly diagnosed with CPT1A deficiency, we included in our cohort 10 Chinese patients who were previously diagnosed. Five of these 12 patients were diagnosed via NBS. All patients exhibited elevated C0 and/or C0/(C16+C18) ratios. No clinical symptoms were observed in the five patients diagnosed via NBS, while all seven patients presented with clinical symptoms, including fever, cough, vomiting, diarrhea, and seizures. Eighteen distinct CPT1A variants were identified, 15 of which have been previously reported. The three novel variants were c.272T>C (p.L91P), c.734G>A (p.R245Q), and c.1336G>A (p.G446S). in silico analysis suggested that all three novel variants were potentially pathogenic. The most common variant was c.2201T>C (p.F734S), with an allelic frequency of 16.67% (4/24). Our findings demonstrated that NBS for CPT1A deficiency is beneficial. The three novel variants expand the mutational spectrum of CPT1A in the Chinese population, and c.2201T>C (p.F734S) may be a potential hotspot CPT1A mutation.

scholarly journals A patient with Gaucher disease and plasma cell dyscrasia: bidirectional impact

Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 389-394
Author(s):  
Ari Zimran ◽  
Rosa Ruchlemer ◽  
Shoshana Revel-Vilk
Keyword(s):  
Gaucher Disease ◽  
Autosomal Recessive ◽  
Hematological Malignancies ◽  
Storage Disease ◽  
Clinical Manifestations ◽  
Plasma Cell Dyscrasia ◽  
Poor Responders ◽  
Autoimmune Thrombocytopenia ◽  
Specific Therapy ◽  
Investigational Therapies

Abstract Patients with Gaucher disease (GD), a rare autosomal recessive glycosphingolipid storage disease, commonly present to hematologists with unexplained splenomegaly, thrombocytopenia, anemia, and bone symptoms. Patients with GD may develop other manifestations, such as autoimmune thrombocytopenia, monoclonal gammopathy, multiple myeloma, or, even more rarely, other hematological malignancies; sometimes they are first diagnosed during an assessment of those disorders. Although the diagnosis and management of patients with GD have significantly evolved over the last 30 years, some patients remain poor responders to GD-specific therapy, needing novel and investigational therapies. Ideally, patients with GD, like patients with other rare diseases, should be managed by a multidisciplinary team expert with the diverse clinical manifestations and potential GD-related or -unrelated comorbidities. The hematology community should be knowledgeable regarding the presentation and the variety of hematologic complications and comorbidities associated with Gaucher disease.

scholarly journals Association of the CD11b rs1143679 polymorphism with systemic lupus erythematosus in the Han Chinese population

2017 ◽  
Vol 46 (3) ◽  
pp. 1008-1014 ◽  
Author(s):  
Chunmei Li ◽  
Fengqing Tong ◽  
Yi Ma ◽  
Kai Qian ◽  
Junyu Zhang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Chinese Population ◽  
Direct Sequencing ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Han Chinese ◽  
Chinese Patients ◽  
Systemic Lupus ◽  
Han Chinese Population

Objective To investigate the association of the CD11b single nucleotide polymorphism (SNP) rs1143679 with systemic lupus erythematosus (SLE) in Han Chinese patients, and to clarify this association with SLE clinical manifestations. Methods PCR–restriction fragment length polymorphism and direct sequencing of CD11b rs1143679 were conducted in 584 patients with SLE and 628 healthy controls in this case–control study to compare genotype and allele frequency distributions. Correlations between CD11b genotypes and clinical manifestations were also determined. Results The frequency of the CD11b rs1143679 GA genotype was 1.89% in Han Chinese patients with SLE, which was much lower than that of European and American populations, but close to the frequency observed in individuals from Hong Kong and Thailand. The CD11b rs1143679 GA genotype was also shown to confer susceptibility to SLE (odds ratio = 4.00, 95% confidence interval = 1.11–14.41). CD11b rs1143679 was found to be significantly associated with nephritis, but not with age of disease onset, arthritis, hematological involvement, or neural lesions. Conclusion CD11b rs1143679 appears to be associated with risk for SLE in the Han Chinese population, and may play an important role in the development of lupus nephritis.

scholarly journals Cerebrotendinous Xanthomatosis, A Rare Metabolic Disease

2012 ◽  
Vol 13 (1) ◽  
pp. 92-93
Author(s):  
Mahmudur Rahman Siddiqui ◽  
Md Sahriar Mahbub ◽  
Quazi Tarikul Islam
Keyword(s):  
Metabolic Disease ◽  
Young Adult ◽  
Male Patient ◽  
Storage Disease ◽  
Cerebrotendinous Xanthomatosis ◽  
Neurological Dysfunction ◽  
Adult Onset ◽  
Childhood Onset ◽  
Lipid Storage Disease ◽  
Psychiatric Disturbances

Cerebrotendinous xanthomatosis (CTX) is a rare genetic lipid storage disease. CTX is characterised by childhood-onset cataract, adolescent to young adult-onset tendon xanthomas and adult-onset progressive neurological dysfunction (dementia, psychiatric disturbances, pyramidal and/or cerebellar signs and seizures). A 32-year-old male patient presented to us with the features of this rare genetic metabolic disorder.DOI: http://dx.doi.org/10.3329/jom.v13i1.8690 JOM 2012; 13(1): 92-93

scholarly journals Multi-imaging study in a patient with cerebrotendinous xanthomatosis: radiology, clinic and pathology correlation of a rare condition

2020 ◽  
Vol 6 (1) ◽  
pp. 20190047
Author(s):  
Giuseppina Dell'Aversano Orabona ◽  
Clemente Dato ◽  
Mariano Oliva ◽  
Lorenzo Ugga ◽  
Maria Teresa Dotti ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Clinical Manifestations ◽  
Imaging Study ◽  
Rare Condition ◽  
Autosomal Recessive Inheritance ◽  
Acid Synthesis ◽  
Cerebrotendinous Xanthomatosis ◽  
Imaging Findings ◽  
Cholic Acids ◽  
Ct And Mri

Cerebrotendinous xanthomatosis (CTX) is a rare metabolic disease with autosomal recessive inheritance. It is caused by mutations of the CYP27A1 gene, which codifies for sterol 27-hydroxylase, an enzyme that is responsible for the synthesis of cholic acids. In CTX, cholic acid synthesis is impaired, leading to accumulation of the precursor chenodessossicholic acid) in various organs and tissues. The clinical manifestations of CTX include chronic diarrhea, early-onset cataracts, tendon xanthomas and neurological disturbances. Therapy with oral chenodessossicholic acid has been shown to provide significantly better outcomes for affected individuals; therefore, recognition of this disease and awareness of its suggestive instrumental signs is extremely important. In this study, we describe the imaging findings in a 43-years-old male who was diagnosed with CTX and studied through ultrasound, CT and MRI. It is important that the neurology and radiology communities are aware of this multi-imaging findings: recognition of them is important, as due to the high variability of the manifestation of this disease; it could impact on early diagnosis of a condition rarely seen, but manageable.

scholarly journals Galactosialidosis in a newborn with a novel mutation in the CTSA gene presenting with transient hyperparathyroidism

2017 ◽  
Vol 20 (2) ◽  
pp. 95-97
Author(s):  
E Okulu ◽  
G Tunc ◽  
T Eminoglu ◽  
O Erdeve ◽  
B Atasay ◽  
...  
Keyword(s):  
Lysosomal Storage Disease ◽  
Autosomal Recessive ◽  
Storage Disease ◽  
Age Of Onset ◽  
Novel Mutation ◽  
Clinical Manifestations ◽  
Inherited Disease ◽  
Lysosomal Storage ◽  
Loss Of Function ◽  
Infantile Form

Abstract Galactosialidosis is a lysosomal storage disease caused by deficiency of protective protein that is encoded by the cathepsin A (CTSA) gene localized on chromosome 20q13.1. Mutations of this gene are the cause of galactosialidosis that result in loss of function of protective protein. Galactosialidosis is an autosomal recessive inherited disease and has been divided into three subtypes based on age of onset and the severity of clinical manifestations. We report an early infantile form of galactosialidosis in a newborn with a novel mutation on the CTSA gene.

Neutral lipid storage disease: genetic disorders caused by mutations in adipose triglyceride lipase/PNPLA2orCGI-58/ABHD5

2009 ◽  
Vol 297 (2) ◽  
pp. E289-E296 ◽  
Author(s):  
Martina Schweiger ◽  
Achim Lass ◽  
Robert Zimmermann ◽  
Thomas O. Eichmann ◽  
Rudolf Zechner
Keyword(s):  
Neutral Lipid ◽  
Storage Disease ◽  
Neutral Lipids ◽  
Genetic Disorders ◽  
Clinical Manifestations ◽  
Lipid Storage ◽  
Adipose Triglyceride Lipase ◽  
Lipid Storage Disease ◽  
Triglyceride Lipase ◽  
Neutral Lipid Storage Disease

Neutral lipid storage disease (NLSD) is a group of autosomal recessive disorders characterized by the excessive accumulation of neutral lipids in multiple tissues. Recently, two genes, adipose triglyceride lipase ( ATGL/ PNPLA2) and comparative gene identification-58 ( CGI-58/ABHD5), have been shown to cause NLSD. ATGL specifically hydrolyzes the first fatty acid from triacylglycerols (TG) and CGI-58/ABHD5 stimulates ATGL activity by a currently unknown mechanism. Mutations in both the ATGL and the CGI-58 genes are associated with systemic TG accumulation, yet the resulting clinical manifestations are not identical. Patients with defective ATGL function suffer from more severe myopathy (NLSDM) than patients with defective CGI-58 function. On the other hand, CGI-58 mutations are always associated with ichthyosis (NLSDI), which was not observed in patients with defective ATGL function. These observations indicate an ATGL-independent function of CGI-58. This review summarizes recent findings with the goal of relating structural variants of ATGL and CGI-58 to functional consequences in lipid metabolism.

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