Nemaline Rods and Complex I Deficiency in Three Infants with Hypotonia, Motor Delay and Failure to Thrive

Abstract

Three infants are described who had nemaline rods on muscle biopsy and isolated deficiency of complex I of the respiratory chain on biochemical analysis. They all manifested failure to thrive from birth, and hypotonia and muscle weakness within the first three months of life. Different genetic defects leading to isolated complex I deficiency have been described associated with a variety of morphological changes on muscle biopsy, but rods have not been described. Nemaline rods have been secondary phenomena in a number of conditions, as well as being the primary abnormality in nemaline myopathy. However, the combination of nemaline rods and complex I deficiency is an association not previously reported.

Complex I deficiency - nemaline rods - developmental delay

References

• 1 Cape C A, Johnson W W, Pitner S E. Nemaline structures in polymyositis.  Neurology. 1970;  20 494-502
• 2 Fukunaga H, Osame M, Igata A. A case of nemaline myopathy with ophthalmoplegia and mitochondrial abnormalities.  J Neurol Sci. 1980;  46 169-177
• 3 Jungbluth H, Sewry C A, Muntoni F. What's new in neuromuscular disorders? The congenital myopathies.  Eur J Paediatr Neurol. 2003;  7 23-30
• 4 Kirby D M, Crawford M, Cleary M A, Dahl H-HM, Dennet X, Thorburn D R. Respiratory chain complex I deficiency. An underdiagnosed energy generation disorder.  Neurology. 1999;  52 1255-1264
• 5 Kirby D M, Salemi R, Sugiana C. et al . NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency.  J Clin Invest. 2004;  in press
• 6 Kornfeld M. Mixed nemaline-mitochondrial “myopathy”.  Acta Neuropathol. 1980;  51 185-189
• 7 Oldfors A, Tulinius M. Mitochondrial encephalomyopathies.  J Neuropath Exp Neurol. 2003;  62 217-227
• 8 Osame M, Kawabuchi M, Igata A, Sugita H. Changes at the neuromuscular junctions in the affected muscles of neostigmine-treated rats, tenotomized rats and a patient with nemaline myopathy.  Acta Histochem Cytochem. 1977;  10 70-80
• 9 Oya Y, Segawa M, Ogawa M, Goto Y, Nonaka I, Kawai M. Congenital nemaline myopathy with mitochondrial abnormalities. An adult case report.  Rinsho Shinkeigaku. 2000;  40 452-458 (in Japanese)
• 10 Pourmand R, Azzarelli B. Adult-onset of nemaline myopathy, associated with cores and abnormal mitochondria.  Muscle Nerve. 1994;  17 1218-1220
• 11 Reimann J, Kunz W S, Veilhaber S, Kappes-Horn K, Schroder R. Mitochondrial dysfunction in myofibrillar myopathy.  Neuropathol Appl Neurobiol. 2003;  29 45-51
• 12 Rustin P, Chretien D, Bourgeron T. et al . Biochemical and molecular investigations in respiratory chain deficiencies.  Clin Chim Acta. 1994;  228 35-51
• 13 Schroder R, Kunz W S, Rouan F. et al . Disorganisation of the desmin cytoskeleton and mitochondrial dysfunction in plectin-related epidermolysis bullosa simplex with muscular dystrophy.  J Neuropathol Exp Neurol. 2002;  61 520-530
• 14 Shapira Y A, Yarom R, Blank A. Nemaline myopathy and a mitochondrial neuromuscular disorder in the one family.  Neuropediatrics. 1981;  12 152-165
• 15 Yamamoto M, Koga Y, Ohtaki E, Nonaka I. Focal cytochrome c oxidase deficiency in various neuromuscular diseases.  J Neurol Sci. 1989;  91 207-213