Related Experiment Video
Updated: Feb 19, 2026
Gait Analysis of Age-dependent Motor Impairments in Mice with Neurodegeneration
Published on: June 18, 2018
Congenital Disorders of Autophagy: What a Pediatric Neurologist Should Know
1Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
Insights
Congenital disorders of autophagy impact brain development, causing neurological issues like intellectual disability and epilepsy. This review details these rare genetic conditions affecting the autophagy pathway.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Autophagy is a crucial cellular process for degrading cellular components, essential for central nervous system development and function.
- Recent discoveries have identified several single-gene disorders linked to the autophagy pathway, impacting neurological health.
- These disorders represent a novel and expanding category of rare genetic conditions.
Purpose of the Study:
- To provide a comprehensive clinical, imaging, and genetic overview of congenital disorders of autophagy.
- To highlight the critical role of the autophagy pathway in childhood-onset neurological diseases.
- To consolidate current knowledge on this evolving group of neurodevelopmental conditions.
Main Methods:
- Literature review of single-gene autophagy disorders.
- Analysis of clinical presentations, neuroimaging findings, and genetic data.
- Synthesis of information on brain malformations, developmental delays, and neurodegeneration.
Main Results:
- Identified specific genes (e.g., EPG5, WDR45, SNX14, ATG5, SQSTM1) associated with distinct autophagy-related neurological disorders.
- Characterized common neurological and neuroimaging features, including brain malformations, white matter tract involvement, and cerebellar abnormalities.
- Observed progressive pathology and a storage disease phenotype in some congenital autophagy disorders.
Conclusions:
- Congenital disorders of autophagy are a significant cause of severe childhood-onset neurological diseases.
- Understanding these genetic conditions is vital for diagnosis and potential therapeutic strategies.
- The autophagy pathway is indispensable for normal brain development and function throughout life.
Abstract:
Autophagy is a fundamental and conserved intracellular pathway that mediates the degradation of macromolecules and organelles in lysosomes. Proper autophagy function is important for central nervous system development and neuronal function. Over the last 5 years, several single gene disorders of the autophagy pathway have emerged: EPG5-associated Vici syndrome, WDR45-associated β-propeller protein-associated neurodegeneration, SNX14-associated autosomal-recessive spinocerebellar ataxia 20, ATG5-associated autosomal-recessive ataxia syndrome, SQSTM1/p62-associated childhood-onset neurodegeneration, and several forms of the hereditary spastic paraplegias. This novel and evolving group of disorders is characterized by prominent central nervous system involvement leading to brain malformations, developmental delay, intellectual disability, epilepsy, movement disorders, and neurodegeneration. Predominant involvement of the long white matter tracts and the cerebellum are anatomic and imaging hallmarks, with common findings that include a thinning of the corpus callosum and cerebellar hypoplasia or atrophy. A storage disease phenotype by clinical or imaging criteria is present in some diseases. Most congenital disorders of autophagy are progressive and over time involve pathology in multiple brain regions. This review provides a detailed clinical, imaging and genetic characterization of congenital disorders of autophagy and highlights the importance of this pathway for childhood-onset neurological diseases.
More Related Videos
Related Concept Videos
01:22Lysosomal Hydrolases
01:27Autophagy
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
01:20Inborn Errors of Metabolism
01:36Delivery Pathways to the Lysosome
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
01:27Protein Import into the Peroxisomes
Peroxisomal Protein Import:
Peroxisomes lack the genetic machinery required to code for their own proteins. Hence, most peroxisomal membrane, lumenal and transmembrane proteins are synthesized in the cytoplasm or ER and transported to the peroxisome...
01:24Pharmacokinetics in Pediatric Patients: Drug Metabolism