Congenital hypertrophic cardiomyopathy, cataract, mitochondrial myopathy and defective oxidative phosphorylation in two siblings with Sengers-like syndrome.
We describe two siblings with a Sengers-like syndrome, who presented with congenital hypertrophic cardiomyopathy, infantile cataract, mitochondrial myopathy, lactic acidosis and normal mental development. A mitochondrial adenine nucleotide translocator 1 (ANT1) defect was detected since the ANT1 protein was not detectable by immmunoblotting in muscle samples of the patients. Additionally to these features of classical Sengers syndrome (OMIM 212350), we found that the mitochondrial oxidative phosphorylation, measured by biochemical analysis, was severely compromised in skeletal muscle in both children. Biochemical and morphological analysis of the fibroblasts revealed normal results. The association of significantly decreased pyruvate oxidation rates, deficient energy production and decreased multiple mitochondrial enzyme-complex activities in the muscle samples of our patients is a new finding which differs from previous results in patients with Sengers syndrome.


CONCLUSIONS
we recommend a muscle biopsy and the biochemical analysis of the oxidative phosphorylation system in patients with muscle hypotonia, cardiomyopathy and congenital or infantile cataract.
Morava
Eva
E
Nijmegen Centre for Mitochondrial Disorders, Department of Paediatrics, University Medical Centre Nijmegen, Nijmegen, The Netherlands. E.Morava@cukz.umcn.nl
Sengers
Rob
R
Ter Laak
Henk
H
Van Den Heuvel
Lambert
L
Janssen
Antoon
A
Trijbels
Frans
F
Cruysberg
Hans
H
Boelen
Carolien
C
Smeitink
Jan
J
D000140:Acidosis, Lactic / Q000150:complications; D033741:Adenine Nucleotide Translocator 1 / Q000172:deficiency; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000150:complications*; D002386:Cataract / Q000150:complications* / Q000151:congenital*; D002648:Child; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D017240:Mitochondrial Myopathies / Q000150:complications* / Q000378:metabolism; D010085:Oxidative Phosphorylation; D035781:Siblings; D013577:Syndrome
D033741:Adenine Nucleotide Translocator 1