Mitochondrial DNA m.3242G > A mutation, an under diagnosed cause of hypertrophic cardiomyopathy and renal tubular dysfunction?
We present two new patients with the recently described mitochondrial m.3242G > A mutation. Although the mutation is situated next to the well known m.3243A > G mutation, the most common alteration associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, the clinical presentation is quite different, but characteristic. All three m.3242G > A patients presented in the neonatal period with hypertrophic and dilated cardiomyopathy, generalized muscle hypotonia and lactic acidosis. Two additionally had creatine kinase elevation, renal tubular acidosis/dysfunction and showed a mild clinical course with a favourable psychomotor development. The third patient had more neurological involvement and died in infancy. The mutation occurred de novo in the two patients where maternal investigations were performed. The combination of hypertrophic cardiomyopathy and renal tubular acidosis/renal tubular dysfunction is clinically distinctive and may represent a separate entity.
Nijmegen Centre for Mitochondrial Disorders at the Department of Pediatrics and the Institute of Genetic and Metabolic Disease, Radboud University Medical Centre, PO Box 9101, Huispost 804, Postbus 9101, 6500 HB Nijmegen, The Netherlands. s.wortmann@cukz.umcn.nl
Saskia B
SB
Wortmann
Michael P
MP
Champion
Lambert
L
van den Heuvel
H
H
Barth
B
B
Trutnau
Kate
K
Craig
Martin
M
Lammens
Michiel F
MF
Schreuder
Robert W
RW
Taylor
Jan A M
JA
Smeitink
Ron A
RA
Wevers
Richard J
RJ
Rodenburg
Eva
E
Morava
D000140:Acidosis, Lactic / Q000209:etiology / Q000235:genetics; D000141:Acidosis, Renal Tubular / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D002311:Cardiomyopathy, Dilated / Q000209:etiology / Q000235:genetics; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D003402:Creatine Kinase / Q000097:blood; D004272:DNA, Mitochondrial / Q000737:chemistry; D005260:Female; D050259:Genes, Mitochondrial / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009123:Muscle Hypotonia / Q000209:etiology / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D012356:RNA, Transfer, Leu / Q000235:genetics; D013577:Syndrome
D004272:DNA, Mitochondrial; D012356:RNA, Transfer, Leu; D003402:Creatine Kinase