Ataxia is a movement disorder that manifests during the execution of purposeful movements. It results from damage to the structures of the cerebellum and its connections or the posterior cords of the spinal cord. It should be noted that, in addition...
Stroke-like episodes (SLEs) are significant clinical manifestations of metabolic disorders affecting the central nervous system. Morphological equivalents presented in neuroimaging procedures are described as stroke-like lesions (SLLs). It is crucial...
Mitochondria are dynamic multitask organelles that function as hubs for many metabolic pathways. They produce most ATP via the oxidative phosphorylation pathway, a critical pathway that the brain relies on its energy need associated with its numerous...
In humans, the phosphorylated pathway (PP) converts the glycolytic intermediate D-3-phosphoglycerate (3-PG) into L-serine through the enzymes 3-phosphoglycerate dehydrogenase, phosphoserine aminotransferase (PSAT) and phosphoserine phosphatase. From...
Ion channel disorders (channelopathies) can affect any organ system in newborns before 2 months of life, including the skeletal muscle and central nervous system. Channelopathies in newborns can manifest as seizure disorders, which is a critical issu...
Riboflavin is the biological precursor of two important flavin cofactors—flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN)—that are critical prosthetic groups in several redox enzymes. While dietary supplementation with ri...
Neurometabolic diseases encompass a diverse group of rare and often progressive genetic disorders affecting the nervous system due to abnormalities in metabolic pathways. These conditions, including mitochondrial disorders, lysosomal storage diseases...
Mitochondria are essential organelles for cellular energy production, playing a central role in driving metabolic processes and supporting critical intracellular functions. Neurometabolic disorders encompass a wide variety of conditions characterized...
Major depressive disorder (MDD) is among the most prevalent mental disorders worldwide. Factors causing the pathogenesis of MDD include gut microbiota (GM), which interacts with the host through the gut–brain axis. In previous studies of GM in...
An 18-year-old man presented with slowly progressive infancy-onset spasticity of the lower limbs and cerebellar ataxia, associated with painless strabismus, intellectual disability, urinary incontinence, bilateral progressive visual loss, and cogniti...
A 38-year-old Brazilian man presented with slowly progressive quadriparesis since age 11 years. He progressed over 15 years with symptoms restricted to the lower limbs, and since then, with a progressive compromise of the upper limbs. His deceased br...
Background: Myoclonus, a sudden brief shock-like involuntary movement, represents a common yet under-recognized manifestation across many inherited metabolic disorders. Although its occurrence has been reported in case series and small cohorts, the o...
Dopa-responsive dystonia (DRD) is a rare movement disorder associated with defective dopamine synthesis. This impairment may be due to the fact of a deficiency in GTP cyclohydrolase I (GTPCHI, GCH1 gene), sepiapterin reductase (SR), tyrosine hydroxyl...
Sporadic occurrence of juvenile-onset necrotizing encephalopathy (SNE) has been previously reported in Yorkshire terriers. However, so far, no causative genetic variant has been found for this breed-specific form of suspected mitochondrial encephalom...
Neurometabolic disorders are an important group of diseases that mostly occur in neonates and infants. They are mainly due to the lack or dysfunction of an enzyme or cofactors necessary for a specific biochemical reaction, which leads to a deficiency...
Rhizomelic chondrodysplasia punctata type 1 (RCDP1) is a peroxisomal disorder characterized by skeletal shortening, intellectual disability, seizures, cataracts, and reduced lifespans. RCDP1 is caused by biallelic loss-of-function variants in PEX7, w...
Alterations in neurometabolism and mitochondria are implicated in the pathophysiology of psychiatric conditions such as mood disorders and schizophrenia. Thus, developing objective biomarkers related to brain mitochondrial function is crucial for the...
Metabolic myopathies are characterized by the dysfunction of several metabolic pathways that results in a deficiency of fuels required to generate energy for muscle contractions [...]
Background/Objectives: The neurometabolic function is controlled by a complex multi-level physiological system that includes neurochemical, hormonal, immunological, sensory, and metabolic components. Functional disorders of monoamine systems are ofte...
Parkinson’s Disease (PD) is the most common neurodegenerative movement disorder whose treatment is symptomatic. No suitable methods for assessing the effects of dopaminergic drugs on disease progression in clinical trials have yet been provided...
Attention deficit hyperactivity disorder (ADHD) is a frequent neurodevelopmental disorder that often persists into adulthood. Methylphenidate (MPH) is the first-line treatment for ADHD; however, despite its wide usage, little is known about its neuro...
6-pyruvoyl tetrahydropterin synthase deficiency (PTPSD) is a rare neurometabolic disease that can be diagnosed in newborn screening (NBS) and is part of the family of tetrahydrobiopterin deficiency disorders (BH4Ds). It is essential to diagnose and t...
Obesity is a systemic metabolic disorder characterized by chronic low-grade inflammation and insulin resistance, with growing evidence indicating that the brain represents a primary and particularly vulnerable target organ. Beyond peripheral metaboli...
Studies over the past 30 years have revealed that adipose tissue is the major endocrine and paracrine organ of the human body. Arguably, adiopobiology has taken its reasonable place in studying obesity and related cardiometabolic diseases (CMDs), inc...
Introduction: Dystonia can present in primary and secondary forms, depending on co-occurring symptoms and syndromic associations. In contrast to primary dystonia, secondary forms of dystonia are often associated with lesions in the putamen or globus...
The tricarboxylic acid (TCA) cycle is the main source of cellular energy and participates in many metabolic pathways in cells. Recent reports indicate that dysfunction of TCA cycle-related enzymes causes human diseases, such as neurometabolic disorde...
Disorders of vesicular trafficking and genetic defects in autophagy play a critical role in the development of metabolic and neurometabolic diseases. These processes govern intracellular transport and lysosomal degradation, thereby maintaining cellul...
Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare autosomal recessive neurometabolic disorder caused by AADC deficiency, an enzyme encoded by the DDC gene. Since the enzyme is involved in the biosynthesis of serotonin and dopamine, its...
Aromatic amino acid decarboxylase (AADC) deficiency is a rare, autosomal recessive neurometabolic disorder caused by mutations in the DDC gene, leading to a deficit of AADC, a pyridoxal 5′-phosphate requiring enzyme that catalyzes the decarboxylation...
Glutaric aciduria type 1 (GA-1) is a rare but treatable autosomal-recessive neurometabolic disorder of lysin metabolism caused by biallelic pathogenic variants in glutaryl-CoA dehydrogenase gene (GCDH) that lead to deficiency of GCDH protein. Without...
Juvenile Amyotrophic Lateral Sclerosis is a genetically heterogeneous neurodegenerative disorder, which is frequently misdiagnosed due to low clinical suspicion and little knowledge about disease characteristics. More than 20 different genetic loci h...
Sepiapterin Reductase Deficiency (SRD) is a rare inherited neurometabolic disorder caused by variants in the SPR gene, which may lead to developmental delays, psychomotor retardation, and cognitive impairments. Two consanguineous North African and Mi...
The introduction of new sequencing approaches into clinical practice has radically changed the diagnostic approach to mitochondrial diseases, significantly improving the molecular definition rate in this group of neurogenetic disorders. At the same t...
Pyridoxine-dependent epilepsy (PDE) is an autosomal recessive neurometabolic disorder due to a deficiency of α-aminoadipic semialdehyde dehydrogenase (mutation in ALDH7A1 gene), more commonly known as antiquitin (ATQ). ATQ is one of the enzymes...
DNA methylation, one of the most well-studied epigenetic modifications, is involved in a wide spectrum of biological processes. Epigenetic mechanisms control cellular morphology and function. Such regulatory mechanisms involve histone modifications,...
20 May 2020
Methylmalonic Acidurias (MMAs) are a group of inborn errors of metabolism (IEMs), specifically of propionate catabolism characterized by gastrointestinal and neurometabolic manifestations resulting from a deficiency in the function of methylmalonyl-C...
9 April 2020
Background: Oftentimes, persistent post traumatic headache (PPTH) and migraine are phenotypically similar and the only clinical feature that differentiate them is the presence of a mild or moderate traumatic brain injury (mTBI). The aim of this study...
A balanced excitatory/inhibitory (E/I) tone is crucial for proper brain function, and disruptions can lead to neurological disorders. This review explores the role of astrocytes in maintaining a balanced E/I tone in the brain, which is crucial for pr...
Despite extensive research, the exact pathomechanisms associated with epileptic seizure formation and propagation have not been elucidated completely. Two-photon imaging (2PI) is a fluorescence-based microscopy technique that, over the years, has bee...
Background: Mild traumatic brain injury (mTBI) is a prevalent neurological condition that results in various physical, emotional, and cognitive impairments. The most common are visual impairments, which affect vision’s perceptual, motor, and se...
Mitochondrial diseases represent the most common inherited neurometabolic disorders, for which no effective therapy currently exists for most patients. The unmet clinical need requires a more comprehensive understanding of the disease mechanisms and...
Deficit of the IDUA (α-L-iduronidase) enzyme causes the lysosomal storage disorder mucopolysaccharidosis type I (MPS I), a rare pediatric neurometabolic disease, due to pathological variants in the IDUA gene and is characterized by the accumulation o...
3-Hydroxy-3-methylglutaric acidemia (HMGA) is a neurometabolic inherited disorder characterized by the predominant accumulation of 3-hydroxy-3-methylglutaric acid (HMG) in the brain and biological fluids of patients. Symptoms often appear in the firs...
The pathophysiology of nonketotic hyperglycinemia (NKH), a rare neuro-metabolic disorder associated with severe brain malformations and life-threatening neurological manifestations, remains incompletely understood. Therefore, a valid human neural mod...
Nutritional ketosis has been proven effective for neurometabolic conditions and disorders linked to metabolic dysregulation. While inducing nutritional ketosis, ketogenic diet (KD) can improve motor performance in the context of certain disease state...
The progressive neurometabolic disorder X-linked adrenoleukodystrophy (ALD) is caused by pathogenic variants in the ABCD1 gene, which encodes the peroxisomal ATP-binding transporter for very-long-chain fatty acids. The clinical spectrum of ALD includ...
Parkinson’s Disease (PD) is the fastest-growing neurological disorder, characterized by the degeneration of dopaminergic neurons. Treatments remain symptomatic, and objective biomarkers for therapeutic response are lacking. This review aims to...
Background: Point mutations in mitochondrial DNA (mtDNA) cause a range of neurometabolic disorders that currently have no curative treatments. The m.8993T>G mutation in the Homo sapiens MT-ATP6 gene leads to neurogenic muscle weakness, ataxia, and...
Background: Although “found down” trauma patients are not subject to any general definition in Germany, the term describes a recurrent clinical picture in the care of adult patients, especially in pre-hospital emergency settings. It is ch...
Background: Transcranial photobiomodulation (t-PBM) is a promising non-invasive therapy for Major Depressive Disorder (MDD). MDD is associated with altered brain metabolism, including changes in N-acetylaspartate (NAA), choline (Cho), and creatine (C...
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