Kisho

Kisho is an information platform, not a medical provider. Nothing on this site constitutes medical advice, diagnosis, or treatment recommendations. All content is aggregated from publicly available sources (including ClinicalTrials.gov, PubMed, FDA.gov, and Orphanet) and is provided for informational purposes only. Clinical trial eligibility, treatment decisions, and any health-related actions should always be discussed with a qualified healthcare professional. Kisho does not endorse any specific therapy, organization, or clinical trial. Terms of use · Privacy policy

neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction

MONDO:0859304

Overview

GeneticsAutosomal recessive · LETM1 (chr 4)

ResearchLimited published research (1 article)

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: Visual impairment; and very common findings: Intellectual disability, Global developmental delay, and Damage to the optic nerve (optic atrophy). 33 total HPO annotations.

Organ System	Phenotype Count	Example Features
Brain and nerves	9	Seizure, Gait ataxia, Ataxia

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.

LETM1 encodes leucine zipper and EF-hand containing transmembrane protein 1 (739 aa). Plays an important role in maintenance of mitochondrial morphology and in mediating either calcium or potassium/proton antiport. Mediates proton-dependent calcium efflux from mitochondrion. Highest expression in Testis (38.5 TPM) and Esophagus Mucosa (37.7 TPM).

Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction is associated with mutations in the LETM1 gene on chromosome 4.

The LETM1 protein participates in LETM1 exchanges protons (mitochondrial intermembrane space) for calcium (mitochondrial matrix), SLC8B1 (NCLX) exchanges sodium (mitochondrial intermembrane space) for calcium (mitochondrial matrix), and Mitochondrial calcium ion transport pathways.

LETM1 is classified as a druggable target (Transporter category) with score 0.0.

Diagnosis

Genetic testing for LETM1 is available. Testing is considered confirmatory for diagnosis.

Prognosis

Phenotype severity distribution: 1 always present feature, 3 very common features, 20 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 neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction.

1 publication has been identified in PubMed for neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction. Research spans Epidemiology / Natural History (100%).

Recent Publications

Abarca-Barriga HH (2025). [PMID: 40251579](https://pubmed.ncbi.nlm.nih.gov/40251579/). *BMC Med Genomics*. [Epidemiology / Natural History]

Data assembled from 5 of 12 sources · Last updated Sep 19, 2026, 3:02 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:620089

Questions for Your Care Team

→Should my partner and I meet with a genetic counselor to discuss carrier status and family planning?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

← Back to All Diseases

neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Prognosis

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Explore clinical features