Abstract
The mitochondrial ribosomes are required for the synthesis of mitochondrial DNA-encoded subunits of the oxidative phosphorylation (OXPHOS) system. Here, we present a neonate with fatal lactic acidosis and combined OXPHOS deficiency caused by a homozygous mutation in MRPS22, a gene encoding a mitochondrial ribosomal small subunit protein. Brain imaging revealed several structural abnormalities, including agenesis of the corpus callosum, multiple periventricular cysts, and suspected intracerebral calcifications. Moreover, echocardiography demonstrated atrial and ventricular septal defects as well as a coronary artery fistula. Our report expands the clinical spectrum of this rare mitochondrial disorder and confirms the severe clinical phenotype associated with this defect.
References
Saada A, Shaag A, Arnon S, Dolfin T, Miller C, Fuchs-Telem D, Lombes A, Elpeleg O (2007) Antenatal mitochondrial disease caused by mitochondrial ribosomal protein (MRPS22) mutation. J Med Genet 44(12):784–786
Smits P, Saada A, Wortmann SB, Heister AJ, Brink M, Pfundt R, Miller C, Haas D, Hantschmann R, Rodenburg RJ, Smeitink JA, van den Heuvel LP (2011) Mutation in mitochondrial ribosomal protein MRPS22 leads to Cornelia de Lange-like phenotype, brain abnormalities and hypertrophic cardiomyopathy. Eur J Hum Genet 19(4):394–399
Janssen AJ, Trijbels FJ, Sengers RC, Smeitink JA, van den Heuvel LP, Wintjes LT, Stoltenborg-Hogenkamp BJ, Rodenburg RJ (2007) Spectrophotometric assay for complex I of the respiratory chain in tissue samples and cultured fibroblasts. Clin Chem 53(4):729–734
Rodenburg RJ (2011) Biochemical diagnosis of mitochondrial disorders. J Inherit Metab Dis 34:283–292
Haack TB, Haberberger B, Frisch EM, Wieland T, Iuso A, Gorza M, Strecker V, Graf E, Mayr JA, Herberg U, Hennermann JB, Klopstock T, Kuhn KA, Ahting U, Sperl W, Wilichowski E, Hoffmann GF, Tesarova M, Hansikova H, Zeman J, Plecko B, Zeviani M, Wittig I, Strom TM, Schuelke M, Freisinger P, Meitinger T, Prokisch H (2012) Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing. J Med Genet 49:277–283
Elstner M, Andreoli C, Klopstock T, Meitinger T, Prokisch H (2009) The mitochondrial proteome database: MitoP2. Methods Enzymol 457:3–20
Robinson BH, Sherwood WG (1984) Lactic acidaemia. J Inherit Metab Dis 7(Suppl 1):69–73
Miller C, Saada A, Shaul N, Shabtai N, Ben-Shalom E, Shaag A, Hershkovitz E, Elpeleg O (2004) Defective mitochondrial translation caused by a ribosomal protein (MRPS16) mutation. Ann Neurol 56(5):734–738
Sugiana C, Pagliarini DJ, McKenzie M, Kirby DM, Salemi R, Abu-Amero KK, Dahl HH, Hutchison WM, Vascotto KA, Smith SM, Newbold RF, Christodoulou J, Calvo S, Mootha VK, Ryan MT, Thorburn DR (2008) Mutation of C20orf7 disrupts complex I assembly and causes lethal neonatal mitochondrial disease. Am J Hum Genet 83(4):468–478
van Straaten HL, van Tintelen JP, Trijbels JM, van den Heuvel LP, Troost D, Rozemuller JM, Duran M, de Vries LS, Schuelke M, Barth PG (2005) Neonatal lactic acidosis, complex I/IV deficiency, and fetal cerebral disruption. Neuropediatrics 36(3):193–199
Funding
This project was supported by the BMBF funded German Network for Mitochondrial Disorders (mitoNET no. 01GM1113C) and by the E-Rare project GENOMIT (01GM1207). Moreover, this work was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation) within the framework of the Munich Cluster for Systems Neurology (EXC 1010 SyNergy).
Author information
Authors and Affiliations
Corresponding authors
Additional information
Fabian Baertling and Tobias B. Haack contributed equally to this work.
Rights and permissions
About this article
Cite this article
Baertling, F., Haack, T.B., Rodenburg, R.J. et al. MRPS22 mutation causes fatal neonatal lactic acidosis with brain and heart abnormalities. Neurogenetics 16, 237–240 (2015). https://doi.org/10.1007/s10048-015-0440-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10048-015-0440-6