Original articleMagnetic resonance imaging in late-onset ornithine transcarbamylase deficiency
Introduction
The urea cycle incorporates excess nitrogen into urea, a water-soluble waste product, in order to prevent the accumulation of toxic nitrogenous metabolites in the body. Ornithine transcarbamylase deficiency (OTCD) is an X-linked disorder, the most common inborn error of metabolism of the urea cycle. The incidence is 1 per 14 000 [1]. OTCD is characterized by signs and symptoms of encephalopathy induced by the accumulation of precursors of urea, principally ammonium and glutamine. Neonatal OTCD presents most commonly in full-term infants at 24–48 h of life with progressive lethargy, hypothermia, and apnea, related to a very high plasma ammonium level. Milder forms of OTCD presenting later in life also occur. Late-onset OTCD occurs most commonly in female carriers with a heterozygous mutation at the OTC locus. In patients with late-onset OTCD, signs of encephalopathy may become evident at any age from infancy to adulthood. Symptoms may include vomiting, abnormal mental status, ataxia, seizures and developmental delay.
The previously reported magnetic resonance imaging (MRI) showed extensive infarct-like abnormalities [2], [3], [4], [5], [6] in patients with late-onset OTCD who had severe clinical manifestations, such as somnolence, seizures and hemiplegia. We sometimes encountered clinically mild patients with late-onset OTCD who had subtle or no parenchymal lesions on MRI. We present the brain MRI findings in a cohort of seven patients with OTCD, and correlate the MRI findings with clinical manifestations.
Section snippets
Patients and methods
Seven OTCD patients (five females and two males), aged 3–27 years, from six different Japanese families, were enrolled in this study. The age at onset of symptoms ranged from 9 months to 11 years. They were classified clinically as having late-onset OTCD. One patient [4] was the mother of another enrolled patient [2]. All patients were being treated with oral benzoate and arginine at the time of MRI. Analysis of the OTC gene revealed a missense mutation in all seven patients, and hepatic OTC
Results
MRI revealed white matter lesions in two patients with clinical stages 2 and 3. T1 and T2 prolongated round lesions were seen in the deep white matter and posterolateral angle of the lateral ventricle in patient 1 (Fig. 1). Small foci of T2 and T1 prolongations in the subcortical white matter were observed in patient 3 (Fig. 2). MRI demonstrated no change in the abnormalities on the first and second scans. Parenchymal lesions, and cerebral and cerebellar atrophy were not found in the other five
Discussion
The previously reported MRI of late-onset OTCD with severe clinical manifestations demonstrated extensive infarct-like abnormalities, sometimes hemispheric, involving both cortex and white matter [2], [3], [4], [5], presumably due to ischemic lesions in the cerebral intervascular boundary zones [4], [6]. The pathophysiological mechanism of central nervous system injury in urea cycle disorders is not completely understood. One theory states that intracerebral accumulation of glutamine is the
Acknowledgements
The authors wish to thank the patients and their families for their contribution to this study. We also thank Mrs. Fuminori Morita, Yoshitada Nakano, Katsuyuki Tanimoto, Shigehiro Ochi and Ms. Tomoko Isobe (Department of Radiology, Chiba University Hospital) for technical support; Drs. Emi Ogawa, Kasumi Nagasawa, Taku Omata, Hiroko Suzuki and Junko Arii (Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, Japan) for their clinical assistance; and Professor A. James
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