Rinsho Shinkeigaku (Clinical Neurology)

Case Report

A case of very long chain acyl-CoA dehydrogenase deficiency diagnosed due to a trigger of hyperemesis gravidarum during pregnancy

Wataru Shiraishi, M.D., Ph.D.1)2), Takahisa Tateishi, M.D., Ph.D.2)3), Shotaro Hayashida, M.D., Ph.D.2), Go Tajima, M.D., Ph.D.4)5), Miyuki Tsumura, M.D., Ph.D.4) and Noriko Isobe, M.D., Ph.D.2)

1) Department of Neurology, Kokura Memorial Hospital
2) Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University
3) Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine
4) Division of Neonatal Screening, Research Institute, National Center for Child Health and Development
5) Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences

A 25-year-old Japanese woman with a history of repeated episodes of rhabdomyolysis since the age of 12 presented with rhabdomyolysis caused by hyperemesis gravidarum. Blood tests showed an elevated serum CK level (11,755 IU⁄l; normal: 30-180 IU⁄l). Carnitine fractionation analysis revealed low levels of total carnitine (18.3 μmol⁄l; normal: 45- 91 μmol⁄l), free carnitine (13.1 μmol⁄l; normal: 36 - 74 μmol⁄l), and acylcarnitine (5.2 μmol⁄l; normal: 6 - 23 μmol⁄l). Tandem mass spectrometry showed high levels of C14:1 acylcarnitine (0.84 nmol⁄ml: normal: <0.4 nmol⁄ml) and a high C14:1⁄C2 ratio of 0.253 (normal: <0.013), indicating a potential diagnosis of very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. Enzyme activity measurement in the patient's peripheral blood lymphocytes confirmed the diagnosis of VLCAD deficiency, with low palmitoyl-CoA dehydrogenase levels (6.5% of normal control value). With the patient's informed consent, acyl-CoA dehydrogenase very long-chain (ACADVL) gene analysis revealed compound heterozygous mutations of c.1332G>A in exon 13 and c.1349G>A (p.R450H) in exon 14. In Japan, neonatal mass screening is performed to detect congenital metabolic diseases. With the introduction of tandem mass screening in 2014, fatty acid metabolism disorders, including VLCAD deficiency, are being detected before the onset of symptoms. However, it is important to note that mass screening cannot detect all cases of this disease. For patients with recurrent rhabdomyolysis, it is essential to consider congenital diseases, including fatty acid metabolism disorders, as a potential diagnosis.
Full Text of this Article in Japanese PDF (1158K)

(CLINICA NEUROL, 63: 656－660, 2023)
key words: rhabdomyolysis, carnitine, very long-chain acyl-CoA dehydrogenase deficiency, hypercreatine kinasemia, hyperemesis gravidarum

(Received: 7-Mar-23)