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Case Reports
. 2012 May;69(5):657-61.
doi: 10.1001/archneurol.2011.2333.

Congenital megaconial myopathy due to a novel defect in the choline kinase Beta gene

Purificacion Gutiérrez Ríos  1 , Arun A Kalra, Jon D Wilson, Kurenai Tanji, Hasan O Akman, Estela Area Gómez, Eric A Schon, Salvatore DiMauro
Affiliations
Case Reports

Congenital megaconial myopathy due to a novel defect in the choline kinase Beta gene

Purificacion Gutiérrez Ríos et al. Arch Neurol. 2012 May.

Abstract

Objectives: To describe the first American patient with a congenital muscle dystrophy characterized by the presence in muscle of gigantic mitochondria displaced to the periphery of the fibers and to stress the potential origin and effects of the mitochondrial changes.

Design: Case report and documentation of a novel mutation in the gene encoding choline kinase beta (CHKB).

Setting: Collaboration between 2 tertiary care academic institutions.

Patient: A 2-year-old African American boy with weakness and psychomotor delay.

Interventions: Detailed clinical and laboratory studies, including muscle biopsy, biochemical analysis of the mitochondrial respiratory chain, and sequencing of the CHKB gene.

Main outcome measures: Definition of unique mitochondrial changes in muscle.

Results: This patient had the same clinical and laboratory features reported in the first cohort of patients, but he harbored a novel CHKB mutation and had isolated cytochrome c oxidase deficiency in muscle.

Conclusions: Besides confirming the phenotype of CHKB mutations, we propose that this disorder affects the mitochondria-associated membrane and the impaired phospholipid metabolism in the mitochondria-associated membrane causes both the abnormal size and displacement of muscle mitochondria.

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Figures

Figure 1.
Figure 1.
Muscle biopsy specimen, light microscopy. A, Variation in fiber size, occasional basophilic regenerating fibers, and irregularly distributed areas of granular basophilic material (hematoxylin-eosin, original magnification ×200). B, The coarse granules were highlighted by the modified Gomori trichrome stain (original magnification ×200). C and D, The granule also stained with cytochrome c oxidase (C) and succinate dehydrogenase (D) (original magnification ×200). Scattered fibers showed absence of staining for cytochrome c oxidase and succinate dehydrogenase except in the areas of abnormal mitochondrial accumulation.
Figure 2.
Figure 2.
Ultrastructural study demonstrated the presence of markedly enlarged mitochondria (“megaconia”) with abnormal cristae (electron microscopy, original magnification ×25 000). No paracrystalline inclusions were noted.
Figure 3.
Figure 3.
Electropherogram showing the p.E292X homozygous mutation detected in the eighth exon of the patient’s choline kinase beta gene (CHKB). Nucleotides are denoted by the colors of the corresponding peaks. Each codon is labeled with the single letter identifying the encoded amino acid.
Figure 4.
Figure 4.
Schematic representation of phospholipid metabolism in the cytosol (Kennedy pathway) and phospholipid trafficking between mitochondria and mitochondria-associated membranes (MAMs). ADP indicates adenosine diphosphate; ATP, adenosine triphosphate; CDP, cytidine diphosphate; CMP, cytidine monophosphate; CTP, cytidine triphosphate; DG, diacylglycerol; and ppi, inorganic phosphate.
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