Neuropediatrics 2013; 44 - FV12_03
DOI: 10.1055/s-0033-1337717

Mitochondriopathy due to mutations in MTFMT: a predominant neurologic phenotype

P Freisinger 1, T Haack 2, R Kopajtich 2, M Johannes 3, U Ahting 2, W Sperl 3, B Plecko 4, E Wilichowski 5, T Meitinger 2, H Prokisch 2
  • 1Klinikum Reutlingen, Klinik für Kinder-und Jugendmedizin, Reutlingen, Germany
  • 2Helmholtz-Zentrum München, Neuherberg, Germany
  • 3Kinderspital, PMU, Salzburg, Austria
  • 4Kinderspital, Zürich, Switzerland
  • 5Kinderklinik, Universität Göttingen, Göttingen, Germany

Aims: Mitochondrial disorders are caused by mutations in structural proteins, assembly factors, cofactors etc. Recently mutations in genes involved in mitochondrial protein synthesis have been identified. The clinical picture of this group of disorders is rather heterogeneous. One gene, MTFMT is involved in formylation of Met-tRNAMet, which is crucial for initiation of mitochondrial translation. Only three patients with mutations in MTFMT have been described so far. We identified with whole exome screening pathogenic mutations in MTFMT in 7 patients from 5 families. The aim was identification of a typical phenotype.

Methods: clinical, radiological, biochemical and genetic comparison.

Results: Clinic: The onset of disease was between 1 month and 3 years. The oldest patient is 24 years old. The neurologic symptoms are similar with variable expression: all patients show muscular hypotonia, movement disorder and mental retardation. Five of seven showed ataxia, four of seven are microcephalic, and one of 7 had seizures. There was no involvement of visceral organs. One patient had a large VSD and suffered from dilated cardiomyopathy. MRI: All patients had symmetrical basal ganglia lesions, five of seven showed white matter involvement of varying degree reaching from small lesions to extensive leukoencephalopathy. Biochemistry: seven of seven had mild-to-moderate lactate elevation in plasma. Analysis of respiratory chain function showed reduced activity of complex I in seven of seven patients, in two of seven combined with complex IV deficiency.

Genetics: Remarkably, all patients carried the mutation c.626C>T either homozygous or compound heterozygous. The other mutations were missense mutations and a deletion.

Conclusion: In mitochondrial disorders with mild lactic acidosis, neurologic symptoms without visceral involvement and isolated or combined complex I deficiency mutations in MTFMT should be considered. All patients up to now carry a mutation c.626 C>T homozygous or compound heterozygous. This should permit initial screening for this mutation.