Metabolic Stroke in Carbamyl Phosphate Synthetase Deficiency

Abstract

Stroke-like episodes with hemiparesis have been described in children with different inherited metabolic diseases. We report the novel observation of a severe stroke as the presenting sign in an 18-month-old girl with carbamyl phosphate synthetase (CPS) deficiency. MRI revealed infarction within the territory of the right middle cerebral artery. Localized 1H-NMR spectroscopy showed elevation of glutamine (at 2.0-2.5 and 3.7 ppm) and lactate within the region of infarction. CPS activity in the liver was reduced (2.5 mU/ mg protein, n = 12-35). On a protein-restricted diet including arginine supplementation, the child has developed well with moderate mental retardation: no neurologic relapses have been observed over a period of 4 years. CPS deficiency has to be added to the list of metabolic diseases that may lead to stroke-like episodes. In every case of unclear hemiparesis in childhood, urea cycle defects should be included in the differential diagnosis.

High prevalence of neonatal presentation in Korean patients with citrullinemia type 1, and their shared mutations

“…The cause of these conditions is unclear, but several hypotheses have been given. Glutamine-induced toxicity and hypoxicischemic injury are associated with cerebral stroke in CTLN1 [29,30]. Concurrent arginine deficiency is also involved, because arginine is a substrate for nitrite oxide synthetase, which has potent vascular relaxant properties [31].…”

Hyperornithinemia–hyperammonemia–homocitrullinuria syndrome with stroke-like imaging presentation: Clinical, biochemical and molecular analysis

“…Stroke or stroke-like clinical and imaging presentations have been described in patients with various inherited metabolic disorders, notably urea cycle defects (UCDs) (4,5), organic acidurias (6), mitochondrial disorders (7), and homocystinuria (8), to the best of our knowledge, MR imaging evidence of stroke-like lesions within the brain in association with HHH syndrome has not been reported in the literature yet. Metabolic screening, thrombosis work up, and MR angiography excluded other possible and more common causes of stroke, such as non-atherosclerotic occlusive arterial or venous disease.…”

“…Stroke and stroke-like lesions are known to occur in patients with different categories of inherited metabolic disorders, notably urea cycle defects (UCDs) [3,4], organic acidurias [5], mitochondrial disorders [6], and homocystinuria [7]. Although UCDs and HHH syndrome share some clinical and biochemical features but, to the best of our knowledge, stroke or stroke-like imaging findings have not been reported in the literature in association with HHH syndrome.…”

Urea cycle disorders: brain MRI and neurological outcome

“…The perirolandic and occipital cortices in older patients are characteristically spared [4], although perirolandic involvement has been described in severe disease [4]. Additionally, when observed, restricted diffusion has been termed metabolic stroke, reflecting tissue injury during the hyperammonemic episode [4][5][6][7].…”