myopathic mitochondrial DNA depletion syndrome
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Introduction
Clinically heterogeneous group of disorders
Pathology
- reduction in mitochondrial DNA (mtDNA) copy number
- may affect single organs, typically muscle or liver, or multiple tissues
- myopathic form: 66-86% mtDNA depletion
- hepatocerebral form: 99% mtDNA depletion in liver
Genetics
- autosomal recessive
- reduction in mitochondrial DNA (mtDNA) copy number
- deletion of SUCLA2 is associated with encephalomyopathy
- defects in RRM2B are associated with encephalomyopathy with renal tubulopathy
- associated with defects in TK2
- associated with defects in DGUOK (type 3)
Clinical manifestations
- various combinations of hypotonia, tubulopathy, seizures, respiratory distress, diarrhea
- myopathic form is slowly progressive, starting in childhood
- hepatocerebral form is presumably more severe
Laboratory
- lactate in plasma
- lactic acidosis is seen in patients with defects in RRM2B or DGUOK [type 3]
- MT-TK gene mutation