• CPT1
• FAO
• ROS
• gastrointestinal tumor
• tumor microenvironment

• Humans
• Fatty Acids/metabolism
• Gastrointestinal Neoplasms/metabolism
• Gastrointestinal Neoplasms/drug therapy
• Gastrointestinal Neoplasms/pathology
• Oxidation-Reduction/drug effects
• Tumor Microenvironment/drug effects
• Antineoplastic Agents/therapeutic use
• Antineoplastic Agents/pharmacology
• Lipid Metabolism/drug effects
• Animals

• 2024M763328 China Postdoctoral Science Foundation
• 81973634 National Natural Science Foundation of China
• 82074245 National Natural Science Foundation of China
• 82204828 National Natural Science Foundation of China
• 82404084 National Natural Science Foundation of China
• 2022KY114 Medical Science and Technology Project of Zhejiang Province
• WKJ-ZJ-2104 Medical Science and Technology Project of Zhejiang Province
• HDMY22H160008 Natural Science Foundation of Zhejiang Province
• 2021YFA0910100 National Key Research and Development Program of China

• Age-related macular degeneration
• Diabetic retinopathy
• Glaucoma
• Inherited retinal diseases
• Lipids
• Metabolism

• Humans
• Retinal Diseases/metabolism
• Retinal Diseases/genetics
• Retinal Diseases/pathology
• Retina/metabolism
• Retina/pathology
• Animals
• Metabolic Networks and Pathways/genetics
• Metabolomics

• Inherited retinal degeneration
• Peroxisomal disorders
• Retina
• Retinitis pigmentosa
• Rod-cone dystrophy
• Syndrome

• Diet
• multidisciplinary care
• retinitis pigmentosa
• syndrome

• refsum
• phyh
• genetics
• genomics
• retina

• Humans
• Refsum Disease
• Phytanic Acid
• Retinitis Pigmentosa/diagnosis
• Retinitis Pigmentosa/genetics
• Exons/genetics
• RNA/genetics
• Mixed Function Oxygenases

• Wellcome Trust

• anosmia
• deafness
• peripheral sensory neuropathy
• refsum disease
• retinitis pigmentosa

• PHYH
• adult Refsum disease
• chronic disease
• dietary modification
• patient registry
• physical function
• phytanic acid
• quality of life
• rare disease
• retinitis pigmentosa

• clinical management
• gene therapy
• genetic counseling
• genetics
• low vision
• low-vision rehabilitation
• retinitis pigmentosa

• 3RS, 7R, 11R-phytanic acid
• antibody
• cytokine
• nitric oxide

• Amyloidosis
• Charcot-Marie-Tooth disease
• Genome
• Inborn error of metabolism
• Inherited neuropathy

• Humans
• Charcot-Marie-Tooth Disease/diagnosis
• Charcot-Marie-Tooth Disease/genetics
• Hereditary Sensory and Motor Neuropathy/diagnosis
• Hereditary Sensory and Motor Neuropathy/genetics

• fatty acid oxidation
• peroxisome
• retinal dystrophy
• retinal lipids
• retinopathy

• R01 EY017017 NEI NIH HHS
• R01 EY032492 NEI NIH HHS

• Joubert syndrome
• Mowat–Wilson disease
• Zellweger spectrum disorder
• cerebral visual impairment
• genetic diagnosis
• genome-wide association study
• multiple sclerosis
• neuromyelitis optica spectrum disorder
• pathology
• phenome-wide association study

• Animals
• Bardet-Biedl Syndrome
• Cerebellum
• Comorbidity
• Neuromyelitis Optica
• Pathology, Molecular

• V111C-189 Taipei Veterans General Hospital
• V111C-085 Taipei Veterans General Hospital
• MOST 108-2314-B-010-042-MY3 Ministry of Science and Technology
• MOST 111-2314-B-A49-057-MY3 Ministry of Science and Technology

• Aging
• Docosahexaenoic acid (DHA)
• Membranes
• Photoreceptors
• Polyunsaturated fatty acid (PUFA)
• RPE
• Rod outer segment
• lipids
• lipids in eye diseases

• Blood-Retinal Barrier
• Humans
• Lipids
• Photoreceptor Cells/metabolism
• Retinal Diseases/metabolism
• Retinal Pigment Epithelium/metabolism

• R01 EY027011 NEI NIH HHS

Infantile Refsum disease is a rare peroxisomal biogenesis disorder characterized by impaired alpha-oxidation and accumulation of phytanic acid in the tissues. Patients often present with fundus changes resembling retinitis pigmentosa, developmental delay, sensorineural hearing loss, ataxia, and hepatomegaly. Traditionally, mainstay treatment for this condition has been a phytanic acid-restricted diet, although supplementation with either docosahexaenoic acid or cholic acid has rarely been described in the literature. We present a case of infantile Refsum disease in a child with retinitis pigmentosa-like ocular findings, sensorineural hearing loss, and self-resolving hepatic disease, who developed novel findings of macular edema refractory to carbonic anhydrase inhibitors. We describe management with a phytanic acid-restricted diet and combination docosahexaenoic acid, and cholic acid therapy, which helped to limit progression of her disease.

The skin is a flexible organ that forms a barrier between the environment and the body's interior; it is involved in the immune response, in protection and regulation, and is a dynamic environment in which skin lipids play an important role in maintaining homeostasis. The different layers of the skin differ in both the composition and amount of lipids. The epidermis displays the best characteristics in this respect. The main lipids in this layer are cholesterol, fatty acids (FAs) and ceramides. FAs can occur in free form and as components of complex molecules. The most poorly characterized FAs are very long-chain fatty acids (VLCFAs) and ultra long-chain fatty acids (ULCFAs). VLCFAs and ULCFAs are among the main components of ceramides and are part of the free fatty acid (FFA) fraction. They are most abundant in the brain, liver, kidneys, and skin. VLCFAs and ULCFAs are responsible for the rigidity and impermeability of membranes, forming the mechanically and chemically strong outer layer of cell membranes. Any changes in the composition and length of the carbon chains of FAs result in a change in their melting point and therefore a change in membrane permeability. One of the factors causing a decrease in the amount of VLCFAs and ULCFAs is an improper diet. Another much more important factor is mutations in the genes which code proteins involved in the metabolism of VLCFAs and ULCFAs—regarding their elongation, their attachment to ceramides and their transformation. These mutations have their clinical consequences in the form of inborn errors in metabolism and neurodegenerative disorders, among others. Some of them are accompanied by skin symptoms such as ichthyosis and ichthyosiform erythroderma. In the following review, the structure of the skin is briefly characterized and the most important lipid components of the skin are presented. The focus is also on providing an overview of selected proteins involved in the metabolism of VLCFAs and ULCFAs in the skin.

• ceramides
• cholesterol
• dermis
• epidermis
• fatty acids
• lipids
• skin

• cutaneous manifestations
• deafness
• genodermatoses
• inherited skin disorders
• syndromic hearing loss

• Dysmyelination
• Knockout mouse
• Neurodegeneration
• Neuronal migration defect
• Peroxisome biogenesis disorders
• Pex (in italic) gene

• Evolution
• PTS2
• Peptide recognition
• Peroxisomes
• Protein transport
• Targeting signals

• Amino Acid Motifs
• Chondrodysplasia Punctata, Rhizomelic/metabolism
• Chondrodysplasia Punctata, Rhizomelic/pathology
• Humans
• Membrane Proteins/metabolism
• Peroxisomal Targeting Signal 2 Receptor/chemistry
• Peroxisomal Targeting Signal 2 Receptor/genetics
• Peroxisomal Targeting Signal 2 Receptor/metabolism
• Peroxisomes/metabolism
• Protein Domains
• Protein Structure, Quaternary
• Protein Transport

• 11R-phytanic aid
• 3RS
• 7R
• IFN-γ production
• NF-κB activity
• PPARα
• T-cell

• hearing loss
• sensorineural
• syndromic

• CMT4C
• Charcot-Marie Tooth disease
• SH3TC2
• autosomal recessive
• hereditary motor and sensory neuropathy

Fish muscle growth is important for the rapidly developing global aquaculture industry, particularly with respect to production and quality. Changes in muscle fibre size are accomplished by altering the balance between protein synthesis and proteolysis. However, our understanding regarding the effects of different protein sources on fish muscle proteins is still limited. Here we report on the proteomic profile of muscle fibre hyperplasia in grass carp fed only with whole faba bean. From the results, a total of 99 significantly changed proteins after muscle hyperplasia increase were identified (p < 0.05, ratio <0.5 or >2). Protein–protein interaction analysis demonstrated the presence of a network containing 56 differentially expressed proteins, and muscle fibre hyperplasia was closely related to a protein–protein network of 12 muscle component proteins. Muscle fibre hyperplasia was also accompanied by decreased abundance in the fatty acid degradation and calcium signalling pathways. In addition, metabolism via the pentose phosphate pathway decreased in grass carp after ingestion of faba bean, leading to haemolysis. These findings could provide a reference for the prevention and treatment of human glucose-6-phosphate dehydrogenase deficiency (“favism”).

The classification of autosomal recessive ataxias represents a significant challenge because of high genetic heterogeneity and complex phenotypes. We conducted a comprehensive systematic review of the literature to examine all recessive ataxias in order to propose a new classification and properly circumscribe this field as new technologies are emerging for comprehensive targeted gene testing.

We searched Pubmed and Embase to identify original articles on recessive forms of ataxia in humans for which a causative gene had been identified. Reference lists and public databases, including OMIM and GeneReviews, were also reviewed. We evaluated the clinical descriptions to determine if ataxia was a core feature of the phenotype and assessed the available evidence on the genotype-phenotype association. Included disorders were classified as primary recessive ataxias, as other complex movement or multisystem disorders with prominent ataxia, or as disorders that may occasionally present with ataxia.

After removal of duplicates, 2354 references were reviewed and assessed for inclusion. A total of 130 articles were completely reviewed and included in this qualitative analysis. The proposed new list of autosomal recessive ataxias includes 45 gene-defined disorders for which ataxia is a core presenting feature. We propose a clinical algorithm based on the associated symptoms.

We present a new classification for autosomal recessive ataxias that brings awareness to their complex phenotypes while providing a unified categorization of this group of disorders. This review should assist in the development of a consensus nomenclature useful in both clinical and research applications.

The online version of this article (doi:10.1186/s40673-017-0061-y) contains supplementary material, which is available to authorized users.

• Cerebellar ataxia
• Classification
• Genetics
• Recessive
• Spinocerebellar degenerations

• Adaptor Proteins, Signal Transducing/genetics
• Animal Feed
• Animals
• Carbohydrate Metabolism
• Comparative Genomic Hybridization
• DNA Copy Number Variations
• Diet
• Dogs/genetics
• Evolution, Molecular
• Gene Dosage
• Mixed Function Oxygenases/genetics
• Pancreatic alpha-Amylases/genetics

Peroxisomes contain numerous enzymatic activities that are important for mammalian physiology. Patients lacking either all peroxisomal functions or a single enzyme or transporter function typically develop severe neurological deficits, which originate from aberrant development of the brain, demyelination and loss of axonal integrity, neuroinflammation or other neurodegenerative processes. Whilst correlating peroxisomal properties with a compilation of pathologies observed in human patients and mouse models lacking all or individual peroxisomal functions, we discuss the importance of peroxisomal metabolites and tissue- and cell type-specific contributions to the observed brain pathologies. This enables us to deconstruct the local and systemic contribution of individual metabolic pathways to specific brain functions. We also review the recently discovered variability of pathological symptoms in cases with unexpectedly mild presentation of peroxisome biogenesis disorders. Finally, we explore the emerging evidence linking peroxisomes to more common neurological disorders such as Alzheimer’s disease, autism and amyotrophic lateral sclerosis. This article is part of a Special Issue entitled: Peroxisomes edited by Ralf Erdmann.

• D-bifunctional protein deficiency
• Lipid metabolism
• Plasmalogen
• Rhizomelic chondrodysplasia punctata
• X-linked adrenoleukodystrophy
• Zellweger spectrum disorder

• ataxia
• cerebellum
• fatty acid
• peroxisome
• plasmalogen

• Animals
• Cerebellum/growth & development
• Cerebellum/physiopathology
• Humans
• Oxidation-Reduction
• Peroxisomal Disorders/physiopathology
• Peroxisomes/physiology

• Genetic testing
• inherited retinal degeneration
• lysosomal disorder
• mitochondrial disorder
• peroxisomal disorder
• primary ciliopathy
• syndromic disease

Alterations in the expression and activity of the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1α (ppargc1a or PGC-1α) have been reported in multiple movement disorders, yet it is unclear how a lack of PGC-1α impacts transcription and function of the cerebellum, a region with high PGC-1α expression. We show here that mice lacking PGC-1α exhibit ataxia in addition to the previously described deficits in motor coordination. Using q-RT-PCR in cerebellar homogenates from PGC-1α^−/− mice, we measured expression of 37 microarray-identified transcripts upregulated by PGC-1α in SH-SY5Y neuroblastoma cells with neuroanatomical overlap with PGC-1α or parvalbumin (PV), a calcium buffer highly expressed by Purkinje cells. We found significant reductions in transcripts with synaptic (complexin1, Cplx1; Pacsin2), structural (neurofilament heavy chain, Nefh), and metabolic (isocitrate dehydrogenase 3a, Idh3a; neutral cholesterol ester hydrolase 1, Nceh1; pyruvate dehydrogenase alpha 1, Pdha1; phytanoyl-CoA hydroxylase, Phyh; ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1, Uqcrfs1) functions. Using conditional deletion of PGC-1α in PV-positive neurons, we determined that 50% of PGC-1α expression and a reduction in a subset of these transcripts could be explained by its concentration in PV-positive neuronal populations in the cerbellum. To determine whether there were functional consequences associated with these changes, we conducted stereological counts and spike rate analysis in Purkinje cells, a cell type rich in PV, from PGC-1α^−/− mice. We observed a significant loss of Purkinje cells by 6 weeks of age, and the remaining Purkinje cells exhibited a 50% reduction in spike rate. Together, these data highlight the complexity of PGC-1α's actions in the central nervous system and suggest that dysfunction in multiple cell types contribute to motor deficits in the context of PGC-1α deficiency.

• Catwalk
• Friedreich Ataxia
• PPARGC1A
• Refsum disease
• ataxia
• cerebellum
• stereology

Autosomal recessive cerebellar ataxias (ARCA) are a clinically and genetically heterogeneous group of rare neurodegenerative disorders characterized by autosomal recessive inheritance and an early age of onset. Progressive ataxia is usually the prominent symptom and is often associated with other neurological or additional features. ARCA classification still remains controversial even though different approaches have been proposed over the years. Furthermore, ARCA molecular diagnosis has been a challenge due to phenotypic overlap and increased genetic heterogeneity observed within this group of disorders. Friedreich’s ataxia and ataxia telangiectasia have been reported as the most frequent and well-studied forms of ARCA. Significant progress in understanding the genetic etiologies of the ARCA has been achieved during the last 15 years. The methodological revolution that has been observed in genetics over the last few years has contributed significantly to the molecular diagnosis of rare diseases including the ARCAs. Development of high throughput technologies has resulted in the identification of new ARCA genes and novel mutations in known ARCA genes. Therefore, an improvement in the molecular diagnosis of ARCA is expected. Moreover, based on the fact that many patients still remain undiagnosed, additional forms of ataxia are expected to be identified. We hereby review the current knowledge on the ARCAs, focused on the genetic findings of the most common forms that were molecularly characterized before the whole exome/genome era, as well as the most recently described forms that have been elucidated with the use of these novel technologies. The significant contribution of whole-exome sequencing or whole-genome sequencing in the molecular diagnosis of ARCAs is discussed.

• Autosomal recessive cerebellar ataxia
• Whole-exome sequencing
• Whole-genome sequencing
• Homozygosity mapping
• Next generation sequencing

• Child
• Humans
• Lysosomal Storage Diseases/diagnosis
• Lysosomal Storage Diseases/physiopathology
• Metabolic Diseases/diagnosis
• Metabolic Diseases/physiopathology
• Muscular Diseases/diagnosis
• Muscular Diseases/physiopathology
• Peripheral Nervous System Diseases/diagnosis
• Peripheral Nervous System Diseases/physiopathology

• Child
• Female
• Humans
• Male
• Peroxisomal Disorders/diagnosis
• Peroxisomal Disorders/genetics
• Peroxisomal Disorders/metabolism
• Pregnancy
• Prenatal Diagnosis