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NEUROLOGY 2004;62:2209-2213
© 2004 American Academy of Neurology

A new diagnostic test for VLCAD deficiency using immunohistochemistry

Y. Ohashi, MD, Y. Hasegawa, MD, K. Murayama, BS, M. Ogawa, MS, T. Hasegawa, MD PhD, M. Kawai, MD, N. Sakata, MD, K. Yoshida, MD PhD, H. Yarita, MD PhD, K. Imai, MD PhD, I. Kumagai, MD PhD, K. Murakami, MD PhD, H. Hasegawa, MD, S. Noguchi, PhD, I. Nonaka, MD PhD, S. Yamaguchi, MD PhD and I. Nishino, MD PhD

From the Department of Neuromuscular Research, National Institute of Neuroscience (Drs. Ohashi, Noguchi, and Nishino, and K. Murayama and M. Ogawa) and the National Hospital of Mental, Nervous and Muscular Disorders (Dr. Nonaka), National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo; the Department of Pediatrics, Keio University (Dr. T. Hasegawa), Shinjuku, Tokyo; the Department of Neurology and Clinical Neuroscience, Yamaguchi University (Drs. Kawai and Sakata), Ube, Yamaguchi; Shinshu University Hospital (Dr. Yoshida), Matsumoto, Nagano; Gunma Central Hospital (Dr. Imai), Maebashi Gunma; Teraoka Memorial Hospital (Dr. Kumagai), Fukuyama, Hiroshima; Tamashima Central Hospital (Dr. Murakami), Kurashiki, Okayama; the Department of Pediatrics, Shimane University (Drs. Y. Hasegawa and Yamaguchi), Izumo, Shimane; the Department of Pediatrics, Kyorin University (Dr. Ohashi), Mitaka, Tokyo; the Division of Clinical and Molecular Genetics, Tatebayashi Kosei Hospital (Dr. Yarita), Tatebayasi, Gunma; and Kitasato Institute Medical Center Hospital (Dr. H. Hasegawa), Kitamoto, Saitama, Japan.

Address correspondence and reprint requests to Dr. Ichizo Nishino, Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187–8502, Japan; e-mail: nishino{at}ncnp.go.jp

Background: Muscle pathology is often unhelpful in elucidating the specific underlying abnormality in patients with metabolic myopathy with rhabdomyolysis, including very-long chain acyl-CoA dehydrogenase (VLCAD) deficiency. Biochemical analyses require large amounts of biopsy samples for each enzyme assay.

Objective: To develop a more efficient diagnostic method for VLCAD deficiency.

Methods: The authors performed immunohistochemical analysis using an antibody to VLCAD on muscles from 344 patients (226 men and 118 women) without a specific diagnosis who had at least one of the following symptoms: myoglobinuria, high CK level, muscle pain, muscle stiffness, sudden infant death syndrome, and Reye-like syndrome.

Results: Immunoreactivity to VLCAD was absent or markedly reduced in 13 patients. Biochemical analyses confirmed that all these patients had low enzymatic activity and reduced amount of protein. They all had the myopathic phenotype. The authors identified homozygous or compound heterozygous mutations in all of them. All recombinant proteins had reduced enzymatic activity except for 128G>A (G43D) and 796C>G (P266A) mutants, indicating that they are neutral polymorphisms.

Conclusions: The new screening method for the detection of VLCAD deficiency using an immunohistochemical technique identified 13 new Japanese patients with VLCAD deficiency.

Received December 9, 2003. Accepted in final form February 18, 2004.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the June 22 issue to find the title link for this article.






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