Successive MRI Findings of Reversible Cerebral White Matter Lesions in a Patient with Cystathionine β-Synthase Deficiency

Successive MRI Findings of Reversible Cerebral White Matter Lesions in a Patient with Cystathionine β-Synthase Deficiency

HIDEO SASAI,¹ NOBUYUKI SHIMOZAWA,² TAKAHIKO ASANO,³ NORIO KAWAMOTO,¹ TAKAHIRO YAMAMOTO,⁴ TAKESHI KIMURA,¹ MINAKO KAWAMOTO,¹ EIKO MATSUI¹ and TOSHIYUKI FUKAO¹

¹Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Gifu, Japan
²Division of Genomics Research, Life Science Research Center, Gifu University, Gifu, Gifu, Japan
³Department of Radiology, Gifu University Hospital, Gifu, Gifu, Japan
⁴Department of Disability Medicine, Graduate School of Medicine, Gifu University, Gifu, Gifu, Japan

Cystathionine β-synthase (CBS) deficiency, well known as classical homocystinuria, is a rare autosomal recessive inborn error of homocysteine and sulfur metabolism. CBS converts homocysteine to cystathionine. The clinical features of untreated CBS deficiency include myopia, ectopia lentis, mental retardation, skeletal anomalies resembling Marfan syndrome, and thromboembolic events. Cerebral white matter lesions (CWMLs), identified in magnetic resonance imaging (MRI), are related to various clinical conditions including ischemia, inflammation, demyelination, infection, a tumor, and metabolic disorders such as phenylketonuria. The presence of CWMLs is, however, believed to be a very rare condition in CBS-deficient patients. Herein, we report reversible CWMLs associated with hypermethioninemia caused by poor protein restriction and betaine therapy in a 21-year-old male with pyridoxine-nonresponsive CBS deficiency. T2-weighted images (T2WI) and fluid-attenuated inversion-recovery (FLAIR) images showed diffuse high signal intensity in subcortical areas extending to the deep white matter. Diffusion-weighted images (DWI) showed high signal intensity, while apparent diffusion coefficient (ADC) map demonstrated decreased ADC value in the lesions. The course of improvement after correct methionine restriction was successively followed by brain MRI. The CWMLs had regressed at 1 month after restriction, and disappeared after 5 months. ADC values were very low before proper methionine restriction, but normalized after 2 months. Use of betaine in the presence of elevated plasma methionine may increase the risk of reversible CWMLs in some CBS-deficient patients.

keywords —— apparent diffusion coefficient; betaine; cystathionine β-synthase deficiency; homocystinuria; reversible cerebral white matter lesions

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Tohoku J. Exp. Med., 2015, 237, 323-327

Correspondence: Hideo Sasai, Department of Pediatrics, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, Gifu 501-1194, Japan.

e-mail: sevenseas0114@hotmail.com