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leukoencephalopathy, hereditary diffuse, with spheroids 2 (HDLS2) - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

leukoencephalopathy, hereditary diffuse, with spheroids 2

MONDO:0030634

Also known as:HDLS2leukoencephalopathy, hereditary diffuse, with spheroids, swedish IIA

Overview

GeneticsAutosomal dominant · AARS1 (chr 16)

ResearchLimited published research (7 articles)

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

Features include always present findings: Difficulty walking (gait disturbance), Muscle stiffness (rigidity), Vegetative state, and Progressive loss of mental abilities (dementia) and others; and common findings: Dystonia, Leukoencephalopathy, Sensory ataxia, and Grasp reflex and others.

Organ System	Phenotype Count	Example Features
Brain and nerves	8	Dystonia, Difficulty walking (gait disturbance), Leukoencephalopathy

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

AARS1 encodes alanyl-tRNA synthetase 1 (968 aa). Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala). Highest expression in Cells EBV-transformed lymphocytes (212.7 TPM) and Cells Cultured fibroblasts (191.4 TPM).

Leukoencephalopathy, hereditary diffuse, with spheroids 2 is associated with mutations in the AARS1 gene on chromosome 16.

AARS1 is classified as a druggable target (Enzyme category) with score 0.6.

90 pathogenic variants reported in AARS1 in ClinVar, including hotspot variant LRG_359p1:p.Arg329His (2-star review).

Variant

Diagnosis

Genetic testing for AARS1 is available. Testing is considered confirmatory for diagnosis.

Prognosis

Phenotype severity distribution: 5 always present features, 7 common features.

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for leukoencephalopathy, hereditary diffuse, with spheroids 2.

7 publications have been identified in PubMed for leukoencephalopathy, hereditary diffuse, with spheroids 2. Research spans Case Report / Case Series (43%), Basic Science / Preclinical (29%), and Epidemiology / Natural History (29%).

Recent Publications

Xie S (2026). [PMID: 42149272](https://pubmed.ncbi.nlm.nih.gov/42149272/). *Neurogenetics*. [Case Report / Case Series]
Chi L (2026). [PMID: 41820324](https://pubmed.ncbi.nlm.nih.gov/41820324/). *Cell Death Discov*. [Basic Science / Preclinical]
Hayer SN (2026). [PMID: 41915097](https://pubmed.ncbi.nlm.nih.gov/41915097/). *Neurol Ther*. [Epidemiology / Natural History]
Lynch DS (2026). [PMID: 42500553](https://pubmed.ncbi.nlm.nih.gov/42500553/). *Brain Commun*. [Epidemiology / Natural History]
Garg D (2025). [PMID: 39957072](https://pubmed.ncbi.nlm.nih.gov/39957072/). *J Mov Disord*. [Case Report / Case Series]

Data assembled from 6 of 12 sources · Last updated Sep 19, 2026, 4:29 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:619661

Questions for Your Care Team

→Should I pursue genetic testing for AARS1, and what would the results mean for my family?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

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leukoencephalopathy, hereditary diffuse, with spheroids 2

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Prognosis

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

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Questions for Your Care Team

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