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Molecular Genetics and Metabolism Mar 2016Peroxisome biogenesis disorders in the Zellweger spectrum (PBD-ZSD) are a heterogeneous group of genetic disorders caused by mutations in PEX genes responsible for... (Review)
Review
Peroxisome biogenesis disorders in the Zellweger spectrum (PBD-ZSD) are a heterogeneous group of genetic disorders caused by mutations in PEX genes responsible for normal peroxisome assembly and functions. As a result of impaired peroxisomal activities, individuals with PBD-ZSD can manifest a complex spectrum of clinical phenotypes that typically result in shortened life spans. The extreme variability in disease manifestation ranging from onset of profound neurologic symptoms in newborns to progressive degenerative disease in adults presents practical challenges in disease diagnosis and medical management. Recent advances in biochemical methods for newborn screening and genetic testing have provided unprecedented opportunities for identifying patients at the earliest possible time and defining the molecular bases for their diseases. Here, we provide an overview of current clinical approaches for the diagnosis of PBD-ZSD and provide broad guidelines for the treatment of disease in its wide variety of forms. Although we anticipate future progress in the development of more effective targeted interventions, the current guidelines are meant to provide a starting point for the management of these complex conditions in the context of personalized health care.
Topics: Adult; Genetic Testing; Hearing Loss, Sensorineural; Humans; Membrane Proteins; Mutation; PHEX Phosphate Regulating Neutral Endopeptidase; Peroxisomal Disorders; Peroxisomes; Phenotype; Practice Guidelines as Topic; Precision Medicine; Retinal Dystrophies; Zellweger Syndrome
PubMed: 26750748
DOI: 10.1016/j.ymgme.2015.12.009 -
International Journal of Molecular... Jan 2017
Topics: Animals; DNA Damage; DNA Repair; Diet; Disease; Epigenesis, Genetic; Humans; Oxidative Stress
PubMed: 28275213
DOI: 10.3390/ijms18010166 -
Brain : a Journal of Neurology Dec 2023Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is an autosomal recessive neurodegenerative disease, usually caused by biallelic AAGGG repeat...
Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is an autosomal recessive neurodegenerative disease, usually caused by biallelic AAGGG repeat expansions in RFC1. In this study, we leveraged whole genome sequencing data from nearly 10 000 individuals recruited within the Genomics England sequencing project to investigate the normal and pathogenic variation of the RFC1 repeat. We identified three novel repeat motifs, AGGGC (n = 6 from five families), AAGGC (n = 2 from one family) and AGAGG (n = 1), associated with CANVAS in the homozygous or compound heterozygous state with the common pathogenic AAGGG expansion. While AAAAG, AAAGGG and AAGAG expansions appear to be benign, we revealed a pathogenic role for large AAAGG repeat configuration expansions (n = 5). Long-read sequencing was used to characterize the entire repeat sequence, and six patients exhibited a pure AGGGC expansion, while the other patients presented complex motifs with AAGGG or AAAGG interruptions. All pathogenic motifs appeared to have arisen from a common haplotype and were predicted to form highly stable G quadruplexes, which have previously been demonstrated to affect gene transcription in other conditions. The assessment of these novel configurations is warranted in CANVAS patients with negative or inconclusive genetic testing. Particular attention should be paid to carriers of compound AAGGG/AAAGG expansions when the AAAGG motif is very large (>500 repeats) or the AAGGG motif is interrupted. Accurate sizing and full sequencing of the satellite repeat with long-read sequencing is recommended in clinically selected cases to enable accurate molecular diagnosis and counsel patients and their families.
Topics: Humans; Bilateral Vestibulopathy; Cerebellar Ataxia; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Syndrome; Vestibular Diseases
PubMed: 37450567
DOI: 10.1093/brain/awad240 -
British Journal of Hospital Medicine... Jan 2023Achalasia, characterised by the absence of peristalsis and failure of relaxation of the lower oesophageal sphincter, is an uncommon degenerative condition that results... (Review)
Review
Achalasia, characterised by the absence of peristalsis and failure of relaxation of the lower oesophageal sphincter, is an uncommon degenerative condition that results in dysphagia. If left untreated it can lead to aspiration, oesophageal perforation, oesophagitis and malnutrition. It has a range of immune, allergic, viral and genetic aetiological causes. Successful diagnosis relies on the use of oesophagogastroduodenoscopy, barium swallow and oesophageal manometry to characterise the severity of the disease and to rule out underlying malignancy. Although no treatment can reverse the degenerative process, therapeutic strategies including lifestyle modification, medication, endoscopic and operative intervention can help to reduce symptoms. This article reviews the latest methods used to investigate and manage achalasia.
Topics: Humans; Esophageal Achalasia; Esophageal Sphincter, Lower; Deglutition Disorders; Manometry; Esophagoscopy
PubMed: 36708337
DOI: 10.12968/hmed.2022.0437 -
Orphanet Journal of Rare Diseases Apr 2017Xeroderma pigmentosum-Cockayne syndrome complex is a very rare multisystem degenerative disorder (Orpha: 220295; OMIM: 278730, 278760, 278780, 610651). Published... (Review)
Review
Xeroderma pigmentosum-Cockayne syndrome complex is a very rare multisystem degenerative disorder (Orpha: 220295; OMIM: 278730, 278760, 278780, 610651). Published information on XP-CS is mostly scattered throughout the literature. We compiled statistics related to symptom prevalence in XP-CS and have written a clinical description of the syndrome. We also drew on clinical practices used in XP and in Cockayne syndrome without XP to aid management of XP-CS.Extensive searches of the literature identified 43 XP-CS patients. The diagnosis had been confirmed with molecular or biochemical methods in 42 of them. Clinical features of each patient were summarized in spreadsheets and summary statistics were generated from this data. XP patients are classified into complementation groups according to the gene that is mutated. There are four groups in XP-CS, and classification was available for 42 patients. Twenty-one were in the XP-G complementation group, 13 in XP-D, 5 in XP-B, and 3 in XP-F. Overall, the clinical features of XP-CS are very similar to those of CS without XP, with the exception of skin cancers in XP-CS. However, one intriguing finding was that cancer incidence was lower in XP-CS compared to XP alone or XP-neurological disorder. The cancer rate in XP-CS was higher than in CS without XP, an unsurprising finding. There is preliminary evidence for the existence of severity groups in XP-CS, as is the case in CS.Although health problems in XP-CS vary both in severity and in when they the first occur, there was overall homogeneity between all complementation groups and putative severity groups. Severely affected patients met fewer milestones and died at younger ages compared to more mildly affected patients.
Topics: Cockayne Syndrome; Humans; Mutation; Xeroderma Pigmentosum
PubMed: 28376890
DOI: 10.1186/s13023-017-0616-2 -
European Review For Medical and... Oct 2022The purpose of this review is to present the latest innovations and current topics in musculoskeletal diagnosis and interventional imaging, with a focus on degenerative... (Review)
Review
OBJECTIVE
The purpose of this review is to present the latest innovations and current topics in musculoskeletal diagnosis and interventional imaging, with a focus on degenerative and inflammatory diseases.
MATERIALS AND METHODS
In this study, the search was conducted through the online databases PubMed and Google Scholar, including articles published in English in the past 15 years, in order to find existing studies, clinical cases, and reviews on the latest innovations and current topics in degenerative and inflammatory musculoskeletal pathologies.
RESULTS
Imaging plays a pivotal role in the diagnosis and treatment of MSK degenerative and inflammatory disease. In the last few years continuous innovations and technological advances have allowed new clinical applications in the management of MSK disorder. Advanced magnetic resonance techniques, the introduction of fusion imaging techniques and new approaches to infiltrative medicine are revolutionizing the clinical and therapeutic approach to degenerative and inflammatory pathologies. Artificial intelligence also increasingly seeks to be applied in all fields of medicine and radiology with increasingly promising results.
CONCLUSIONS
Imaging modalities undergo continuous innovations and revolutions due to technological advances, with direct repercussions on clinical applications and new therapeutic potential through interventional radiology techniques. In recent years, there have been particular innovations in the context of musculoskeletal imaging of degenerative and inflammatory diseases, both for diagnosis and intervention.
Topics: Humans; Artificial Intelligence; Musculoskeletal Diseases; Radiology; Radiography; Magnetic Resonance Imaging
PubMed: 36263576
DOI: 10.26355/eurrev_202210_29877 -
Seminars in Neurology Jul 2012The idiopathic inflammatory myopathies are a group of rare disorders that share many similarities. These include dermatomyositis (DM), polymyositis (PM), necrotizing... (Review)
Review
The idiopathic inflammatory myopathies are a group of rare disorders that share many similarities. These include dermatomyositis (DM), polymyositis (PM), necrotizing myopathy (NM), and sporadic inclusion body myositis (IBM). Inclusion body myositis is the most common idiopathic inflammatory myopathy after age 50 and it presents with chronic proximal leg and distal arm asymmetric mucle weakness. Despite similarities with PM, it is likely that IBM is primarily a degenerative disorder rather than an inflammatory muscle disease. Inclusion body myositis is associated with a modest degree of creatine kinase (CK) elevation and an abnormal electromyogram demonstrating an irritative myopathy with some chronicity. The muscle histopathology demonstrates inflammatory exudates surrounding and invading nonnecrotic muscle fibers often times accompanied by rimmed vacuoles. In this chapter, we review sporadic IBM. We also examine past, essentially negative, clinical trials in IBM and review ongoing clinical trials. For further details on DM, PM, and NM, the reader is referred to the idiopathic inflammatory myopathies chapter.
Topics: Electrophysiological Phenomena; Exercise Therapy; Humans; Muscle, Skeletal; Myositis, Inclusion Body; Physical Therapy Modalities; Prognosis
PubMed: 23117948
DOI: 10.1055/s-0032-1329197 -
The Psychiatric Clinics of North America Dec 1997Huntington's disease is a genetically inherited degenerative neuropsychiatric disorder, characterized by motor alterations, including involuntary movements such as... (Review)
Review
Huntington's disease is a genetically inherited degenerative neuropsychiatric disorder, characterized by motor alterations, including involuntary movements such as chorea, dementia and psychiatric disturbances. In this article, the authors review the clinical features of the disease. They also analyze some genetic and pathophysiologic aspects, that can help to improve our understanding of this disorder involving the basal ganglia.
Topics: Basal Ganglia; Behavioral Symptoms; Disease Progression; Genetic Markers; Humans; Huntington Disease; Nerve Degeneration; Palliative Care
PubMed: 9443350
DOI: 10.1016/s0193-953x(05)70345-2 -
Endokrynologia Polska 2021Wolfram syndrome (WFS) is a neurological and endocrinological degenerative disorder, also known as DIDMOAD (Diabetes Insipidus, early-onset Diabetes Mellitus,...
INTRODUCTION
Wolfram syndrome (WFS) is a neurological and endocrinological degenerative disorder, also known as DIDMOAD (Diabetes Insipidus, early-onset Diabetes Mellitus, progressive Optic Atrophy, and Deafness) syndrome. It is an autosomal recessive disorder, mostly involving the Wolfram syndrome 1 gene (WFS1). The phenotypic pleiomorphism, rarity, and molecular complexity complicate the follow-up of these patients.
MATERIAL AND METHODS
We aimed to describe the clinical characteristics and the follow-up of 11 patients with this disorder. We retrospectively analysed all WFS patients diagnosed between 1990 and 2020 in the Centro Hospitalar São João, a tertiary hospital in Northern Portugal.
RESULTS
Eleven patients were included. Four patients had all 4 components of DIDMOAD. The presentation was diabetes mellitus (DM) in 9 patients, optic atrophy (OA) in another patient, and diabetes insipidus (DI) in another one. The median age of DM and OA diagnosis was 6 and 14 years, respectively. Nine patients had diabetes mellitus, and the other 2 patients had impaired glucose tolerance. All patients had OA. Four patients presented DI, all of them diagnosed in adolescence. Four patients had hearing impairment, 5 had urological abnormalities, 5 had neurological disorders, and 8 had psychiatry disorders. Eight patients had a broad spectrum of recessive mutations in WFS1.
CONCLUSION
The information obtained in this study can facilitate further research in an attempt to improve prevention strategies for this devastating disease.
Topics: Adolescent; Child; Diabetes Insipidus; Humans; Membrane Proteins; Optic Atrophy; Portugal; Retrospective Studies; Wolfram Syndrome
PubMed: 34010437
DOI: 10.5603/EP.a2021.0038