-
Physiological Reviews Jan 2023Peroxisomes are subcellular organelles that play a central role in human physiology by catalyzing a range of unique metabolic functions. The importance of peroxisomes... (Review)
Review
Peroxisomes are subcellular organelles that play a central role in human physiology by catalyzing a range of unique metabolic functions. The importance of peroxisomes for human health is exemplified by the existence of a group of usually severe diseases caused by an impairment in one or more peroxisomal functions. Among others these include the Zellweger spectrum disorders, X-linked adrenoleukodystrophy, and Refsum disease. To fulfill their role in metabolism, peroxisomes require continued interaction with other subcellular organelles including lipid droplets, lysosomes, the endoplasmic reticulum, and mitochondria. In recent years it has become clear that the metabolic alliance between peroxisomes and other organelles requires the active participation of tethering proteins to bring the organelles physically closer together, thereby achieving efficient transfer of metabolites. This review intends to describe the current state of knowledge about the metabolic role of peroxisomes in humans, with particular emphasis on the metabolic partnership between peroxisomes and other organelles and the consequences of genetic defects in these processes. We also describe the biogenesis of peroxisomes and the consequences of the multiple genetic defects therein. In addition, we discuss the functional role of peroxisomes in different organs and tissues and include relevant information derived from model systems, notably peroxisomal mouse models. Finally, we pay particular attention to a hitherto underrated role of peroxisomes in viral infections.
Topics: Animals; Humans; Mice; Peroxisomes
PubMed: 35951481
DOI: 10.1152/physrev.00051.2021 -
Journal of Internal Medicine Oct 2021We have reviewed the literature and have identified more than 100 diseases or conditions that are associated with raised concentrations of plasma total homocysteine. The... (Review)
Review
We have reviewed the literature and have identified more than 100 diseases or conditions that are associated with raised concentrations of plasma total homocysteine. The commonest associations are with cardiovascular diseases and diseases of the central nervous system, but a large number of developmental and age-related conditions are also associated. Few other disease biomarkers have so many associations. The clinical importance of these associations becomes especially relevant if lowering plasma total homocysteine by B vitamin treatment can prevent disease and so improve health. Five diseases can at least in part be prevented by lowering total homocysteine: neural tube defects, impaired childhood cognition, macular degeneration, primary stroke, and cognitive impairment in the elderly. We conclude from our review that total homocysteine values in adults of 10 μmol/L or below are probably safe, but that values of 11 μmol/L or above may justify intervention. Homocysteine is more than a disease biomarker: it is a guide for the prevention of disease.
Topics: Adult; Aged; Biomarkers; Child; Cognitive Dysfunction; Homocysteine; Humans; Macular Degeneration; Neural Tube Defects; Stroke; Vitamin B Complex
PubMed: 33660358
DOI: 10.1111/joim.13279 -
Movement Disorders Clinical Practice Jul 2021Several conditions represented mainly by movement disorders are associated with cardiac disease, which can be overlooked in clinical practice in the context of a... (Review)
Review
BACKGROUND
Several conditions represented mainly by movement disorders are associated with cardiac disease, which can be overlooked in clinical practice in the context of a prominent primary neurological disorder.
OBJECTIVES
To review neurological conditions that combine movement disorders and primary cardiac involvement.
METHODS
A comprehensive and structured literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria was conducted to identify disorders combining movement disorders and cardiac disease.
RESULTS
Some movement disorders are commonly or prominently associated with cardiac disease. Neurological and cardiac symptoms may share underlying physiopathological mechanisms in diseases, such as Friedreich's ataxia and Wilson's disease, and in certain metabolic disorders, including Refsum disease, Gaucher disease, a congenital disorder of glycosylation, or cerebrotendinous xanthomatosis. In certain conditions, such as Sydenham's chorea or dilated cardiomyopathy with ataxia syndrome (ATX-), heart involvement can present early in the course of disease, whereas in others such as Friedreich's ataxia or Refsum disease, cardiac symptoms tend to present in later stages. In another 68 acquired or inherited conditions, cardiac involvement or movement disorders are seldom reported.
CONCLUSIONS
As cardiac disease is part of the phenotypic spectrum of several movement disorders, heart involvement should be carefully investigated and increased awareness of this association encouraged as it may represent a leading cause of morbidity and mortality.
PubMed: 34307738
DOI: 10.1002/mdc3.13188 -
Seminars in Neurology Feb 2012The combination of neurologic disease and ichthyosis defines a heterogeneous group of rare inherited disorders that present in infancy through early adulthood. Although... (Review)
Review
The combination of neurologic disease and ichthyosis defines a heterogeneous group of rare inherited disorders that present in infancy through early adulthood. Although affected patients share the cutaneous feature of ichthyosis, there is variability in the nature and severity of neurologic disease. Impaired cognition, spasticity, sensorineural deafness, visual impairment, and/or seizures are the primary neurologic findings. Most of these disorders are caused by genetic defects in lipid metabolism, glycoprotein synthesis, or intracellular vesicle trafficking. The clinical features of some of the neuro-ichthyoses are distinct enough to allow their clinical recognition, but confirmatory biochemical or genetic tests are necessary for accurate diagnosis. Treatment of the ichthyosis is largely symptomatic, and except for Refsum's disease, there are no effective pathogenesis-based therapies for the neurologic disease.
Topics: Humans; Ichthyosis; Infant; Infant, Newborn; Lipid Metabolism; Mutation; Skin; Syndrome
PubMed: 22422210
DOI: 10.1055/s-0032-1306390 -
Annals of Oncology : Official Journal... Jun 2022Uncertainty prevails about the magnitude of excess risk of small bowel cancer in patients with inflammatory bowel disease (IBD).
BACKGROUND
Uncertainty prevails about the magnitude of excess risk of small bowel cancer in patients with inflammatory bowel disease (IBD).
PATIENTS AND METHODS
To quantify the risk of small bowel adenocarcinoma and neuroendocrine tumors in patients with ulcerative colitis (UC) and Crohn's disease (CD), we undertook a population-based cohort study of all patients with IBD diagnosed in Norway and Sweden from 1987 to 2016. Patients were followed through linkage to national registers. We calculated standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) of small bowel adenocarcinomas and neuroendocrine tumors for patients with CD and UC. We excluded the first year of follow-up to reduce reverse causality.
RESULTS
Among 142 008 patients with a median follow-up of 10.0 years, we identified 66 adenocarcinomas and 57 neuroendocrine tumors in the small bowel. The SIR of small bowel adenocarcinoma was 8.3 (95% CI 5.9-11.3) in CD and 2.0 (95% CI 1.2-3.1) in UC. The incidence rates of adenocarcinomas were highest in CD with stricturing disease and extent limited to the small bowel, at 14.7 (95% CI 8.2-24.2) and 15.8 (95% CI 8.4-27.0) per 100 000 person-years, respectively. The SIR of neuroendocrine tumors was 2.5 (95% CI 1.5-3.9) in CD and 2.0 (95% CI 1.4-2.8) in UC.
CONCLUSIONS
Patients with CD experienced an eightfold increased risk of small bowel adenocarcinomas, patients with both UC and CD experienced an about twofold increased risk of neuroendocrine tumors, and patients with UC experienced a twofold increased risk of small bowel adenocarcinoma. The small absolute excess cancer risk suggests that active surveillance to diagnose small intestinal cancer early is unlikely to be cost-effective.
Topics: Adenocarcinoma; Cohort Studies; Colitis, Ulcerative; Crohn Disease; Humans; Incidence; Inflammatory Bowel Diseases; Neuroendocrine Tumors; Risk Factors
PubMed: 35276334
DOI: 10.1016/j.annonc.2022.02.226 -
Journal of Neurology, Neurosurgery, and... Jan 1986Nine cases of neonatal adrenoleukodystrophy are described. All patients had abnormal facial features, moderate to severe hypotonia, hepatomegaly, and retinitis...
Nine cases of neonatal adrenoleukodystrophy are described. All patients had abnormal facial features, moderate to severe hypotonia, hepatomegaly, and retinitis pigmentosa. The clinical course was rapidly progressive in six cases and more protracted in three others. Biological signs of adrenal insufficiency were present in five cases. CT scan showed a demyelinating process in four patients. Trilamellar inclusions were found in the liver of four cases and dark and complex lipidic inclusions in three other cases. In the three necropsied patients there was severe alteration of the white matter involving particularly the cerebellum in two cases. Gyral and cytoarchitectonic disturbances were absent in all three cases. Increased plasma levels of very long chain fatty acids (8/8), phytanic acid (7/8) and bile fluid trihydroxycoprostanic acid (2/4) confirmed the deficiency of multiple peroxisomal enzymes. Clinical, histopathological and biochemical findings of these nine cases are compared to those reported in other neonatal adrenoleukodystrophy cases and to those of other neonatal peroxisomal disorders, that is cerebro-hepato-renal syndrome of Zellweger and infantile Refsum's disease.
Topics: Adrenal Cortex; Adrenoleukodystrophy; Biopsy; Brain; Diagnosis, Differential; Diffuse Cerebral Sclerosis of Schilder; Female; Humans; Infant; Infant, Newborn; Liver; Male; Microbodies; Refsum Disease; Spinal Nerves
PubMed: 2420940
DOI: 10.1136/jnnp.49.1.77