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Complex II deficiency is a mitochondrial disease. Mitochondria are specialized compartments in cells that create more than 90% of the energy needed by the body. In mitochondrial diseases, the mitochondria don't work correctly resulting in less energy in the cell, cell injury and cell death. The signs and symptoms of mitochondrial complex II deficiency can vary greatly from severe life-threatening symptoms in infancy to muscle disease beginning in adulthood. Complex II deficiency can be caused by mutations in the SDHA, SDHB, SDHD, or SDHAF1 genes. In many cases the underlying gene mutations cannot be identified. Complex II deficiency is inherited in an autosomal recessive fashion. Complex II deficiency gene mutation carriers may be at an increased risk for certain cancers.
Features include always present findings: Elevated lactate:pyruvate ratio, Decreased activity of mitochondrial complex II, Truncal ataxia, and Increased circulating lactate concentration and others; and common findings: Babinski sign, Loss of previously acquired skills (developmental regression), Thickened heart muscle (hypertrophic cardiomyopathy), and Spasticity and others. 76 total HPO annotations.
Organ System | Phenotype Count | Example Features |
|---|---|---|
Brain and nerves | 22 | Dystonia, Seizure, Ataxia |
Muscles | 15 | Flexion contracture, Abnormal mitochondria in muscle tissue, Muscle weakness |
Eyes | 7 | Pigmentary retinopathy, Nystagmus, Ptosis |
Heart and blood vessels | 7 | Enlarged and weakened heart (dilated cardiomyopathy), Left ventricular noncompaction, Thickened heart muscle (hypertrophic cardiomyopathy) |
Growth and development | 5 | Short stature, Weight loss, Proportionate short stature |
Lab test results | 2 | Decreased activity of mitochondrial complex II, Increased circulating lactate concentration |
Arms and legs | 2 | Lower limb hypertonia, Upper limb hyperreflexia |
Bones and joints | 2 | Skeletal myopathy, Skeletal muscle atrophy |
Pregnancy and birth | 1 | Neonatal hypotonia |
Digestive system | 1 | Feeding difficulties in infancy |
Head and neck | 1 | Mild microcephaly |
SDHA function has not been fully characterized.
Mitochondrial complex II deficiency, nuclear type 1 is associated with mutations in the SDHA gene on chromosome 5.
Genetic testing for SDHA is available. Testing is considered confirmatory for diagnosis.
Phenotype severity distribution: 5 always present features, 24 common features.
Estimated prevalence: <1 in 1,000,000 (VERY_RARE).
No clinical trials have been registered for mitochondrial complex II deficiency, nuclear type 1.
3 publications have been identified in PubMed for mitochondrial complex II deficiency, nuclear type 1. Research spans Basic Science / Preclinical (67%) and Review / Meta-Analysis (33%).
Sillapachaiyaporn C (2026). [PMID: 41555429](https://pubmed.ncbi.nlm.nih.gov/41555429/). *Cell Commun Signal*. [Basic Science / Preclinical]
Wang J (2025). [PMID: 40285898](https://pubmed.ncbi.nlm.nih.gov/40285898/). *Cell Biol Toxicol*. [Review / Meta-Analysis]
Zhang F (2024). [PMID: 39727307](https://pubmed.ncbi.nlm.nih.gov/39727307/). *Elife*. [Basic Science / Preclinical]
Data assembled from 6 of 12 sources · Last updated Sep 18, 2026, 7:14 PM UTC
Online Mendelian Inheritance in Man
European rare disease database
Genetic and Rare Diseases Info Center