Indication
This is a clinical test intended for HelpPurposes or indications for the test. Lab-provided.: Diagnosis
Autosomal recessive mitochondrial complex III deficiency is a severe multisystem disorder with onset at birth of lactic acidosis, hypotonia, hypoglycemia, failure to thrive, encephalopathy, and delayed psychomotor development. Visceral involvement, including hepatopathy and renal tubulopathy, may also occur. Many patients die in early childhood, but some may show longer survival (de Lonlay et al., 2001; De Meirleir et al., 2003).
Genetic Heterogeneity of Mitochondrial Complex III Deficiency
Mitochondrial complex III deficiency can be caused by mutation in several different nuclear-encoded genes. See MC3DN2 (615157), caused by mutation in the TTC19 gene (613814) on chromosome 17p12; MC3DN3 (615158), caused by mutation in the UQCRB gene (191330) on chromosome 8q; MC3DN4 (615159), caused by mutation in the UQCRQ gene (612080) on chromosome 5q31; MC3DN5 (615160), caused by mutation in the UQCRC2 gene (191329) on chromosome 16p12; MC3DN6 (615453), caused by mutation in the CYC1 gene (123980) on chromosome 8q24; MC3DN7 (615824), caused by mutation in the UQCC2 gene (614461) on chromosome 6p21; MC3DN8 (615838), caused by mutation in the LYRM7 gene (615831) on chromosome 5q23; MC3DN9 (616111), caused by mutation in the UQCC3 gene (616097) on chromosome 11q12; and MC3DN10 (618775), caused by mutation in the UQCRFS1 gene (191327) on chromosome 19q12.
See also MTYCB (516020) for a discussion of a milder phenotype associated with isolated mitochondrial complex III deficiency and mutations in a mitochondrial-encoded gene.
- Lactic acidosis
- Ptosis
- Hypertrophic cardiomyopathy
- Cerebellar ataxia
- Cholangitis
- Cholestasis
- Depression
- Gliosis
- Hallucinations
- Hyperglycemia
- Hypoglycemia
- Hypotonia
- Spasticity
- Rhabdomyolysis
- Seizure
- Interstitial nephritis
- Cataract
- EEG abnormality
- Muscle weakness
- Hyperreflexia
- Metabolic acidosis
- Decreased liver function
- Cerebral atrophy
- Aminoaciduria
- Brittle hair
- Exercise intolerance
- Global developmental delay
- Cerebellar atrophy
- Elevated circulating alkaline phosphatase concentration
- Hearing impairment
- Increased serum lactate
- Severe lactic acidosis
- Recurrent hypoglycemia
- Elevated hepatic transaminase
- Periportal fibrosis
- Microvesicular hepatic steatosis
- Mitochondrial encephalopathy
- Axial hypotonia
- Generalized hypotonia
- Hypertyrosinemia
- Failure to thrive
- Feeding difficulties in infancy
- Hepatic steatosis
- Decreased activity of mitochondrial complex III
- Ragged-red muscle fibers
- Intellectual disability
- Delayed CNS myelination
- Decreased mitochondrial complex III activity in liver tissue
- Lacticaciduria
- Elevated gamma-glutamyltransferase level
- Rod-cone dystrophy
- Elevated lactate:pyruvate ratio
- Emotional lability
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This panel should be performed in all individuals suspected of having an overlapping clinical phenotype. Confirmation of a clinical diagnosis through genetic testing can allow for genetic counseling and may direct medical management. Genetic counseling can provide a patient and/or family with the natural history of the condition, identify at-risk family members, provide reproductive risks as well as preconception/prenatal options, and allow for appropriate referral for patient support and/or resources.
Citations
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