A novel mitochondrial G8313A mutation associated with prominent initial gastrointestinal symptoms and progressive encephaloneuropathy

Ashok Verma, David A. Piccoli, Eduardo Bonilla, Gerard T. Berry, Salvatore DiMauro, Carlos T Moraes

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

We describe a childhood mitochondrial disorder in which the clinical symptoms began and remained confined to the gastrointestinal (GI) system during the first 4 y. Seizures heralded the onset of progressive encephalopathy at age 7. Peripheral neuropathy, retinitis pigmentosa, and neural deafness developed subsequently. Laboratory investigations disclosed elevated levels of plasma lactate, and a muscle biopsy revealed ragged red fibers lacking cytochrome c oxidase activity and diminished levels of respiratory chain enzyme complexes. Molecular genetic tests failed to show any of the previously reported pathogenic mitochondrial DNA (mtDNA) mutations. We therefore screened the whole mitochondrial genome by coupling restriction digestions with single-strand conformational polymorphism (SSCP) patterns. We identified a unique SSCP in the segment that encompassed the tRNA(Lys) gene, and direct sequencing of this segment revealed a G → A transition at an evolutionarily conserved nucleotide at mtDNA position 8313. This G8313A transition was heteroplasmic in muscle and fibroblasts of the patient, but was absent in the white blood cells and platelets from his maternal relatives. This report illustrates how GI symptoms can be the initial manifestation in a mitochondrial disorder and suggests that mitochondrial dysfunction should be considered in differentials of unexplained chronic GI symptoms, especially when lactic acidosis or other unrelated clinical signs or symptoms are present.

Original languageEnglish
Pages (from-to)448-454
Number of pages7
JournalPediatric Research
Volume42
Issue number4
StatePublished - Oct 1 1997

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Mitochondrial Diseases
Mitochondrial DNA
RNA, Transfer, Lys
Muscles
Lactic Acidosis
Mutation
Retinitis Pigmentosa
Mitochondrial Genome
Brain Diseases
Deafness
Peripheral Nervous System Diseases
Electron Transport Complex IV
Electron Transport
Signs and Symptoms
Molecular Biology
Digestion
Lactic Acid
Seizures
Leukocytes
Blood Platelets

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

A novel mitochondrial G8313A mutation associated with prominent initial gastrointestinal symptoms and progressive encephaloneuropathy. / Verma, Ashok; Piccoli, David A.; Bonilla, Eduardo; Berry, Gerard T.; DiMauro, Salvatore; Moraes, Carlos T.

In: Pediatric Research, Vol. 42, No. 4, 01.10.1997, p. 448-454.

Research output: Contribution to journalArticle

Verma, Ashok ; Piccoli, David A. ; Bonilla, Eduardo ; Berry, Gerard T. ; DiMauro, Salvatore ; Moraes, Carlos T. / A novel mitochondrial G8313A mutation associated with prominent initial gastrointestinal symptoms and progressive encephaloneuropathy. In: Pediatric Research. 1997 ; Vol. 42, No. 4. pp. 448-454.
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