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Imaging Findings Associated With Methylmalonic Aciduria
Pediatric Neurology 50 (2014) 435e436
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Visual Diagnosis
Imaging Findings Associated With Methylmalonic Aciduria Sedat Is¸ikay MD a, *, Levent Temel MD b, Mehmet Keskin MD c a
Department of Pediatric Neurology, Gaziantep Children’s Hospital, Gaziantep, Turkey Department of Pediatrics, Gaziantep Children’s Hospital, Gaziantep, Turkey c Department of Pediatric Endocrinology and Metabolisms, Gaziantep University, Gaziantep, Turkey b
The conversion of methylmalonic acid to succinic acid requires both an apoenzyme (methylmalonyl CoA mutase) and a coenzyme (adenosylcobalamin). Deficiency of either entity results in accumulation of methylmalonic acid derivatives in physiologic fluids. The basal ganglia, predominantly globi pallidi, are particularly sensitive to metabolic dysfunction and are thus the main targets for brain injury in this condition. A 7-month-old boy was admitted with a 2-day history of vomiting and lethargy. Clinical examinations revealed
tachypnea, tachycardia, lethargy, hypotonia, dehydration, and failure to thrive. Blood gas analysis showed severe metabolic acidosis with low pH (7.01) and bicarbonate (7.5 mmol/L). Serum ammonia was 214 mg/dL (29-70 mg/dL); serum lactate was 25 mg/dL (5-22 mg/dL). Computed tomography showed symmetrical hypodensities in the globi pallidi and periventricular areas along with bilateral frontal atrophy and Sylvian hypoplasia. T2-weighted magnetic resonance images revealed symmetric high signals in both globi pallidi (Figure). T1-weighted images were not
FIGURE. Axial computed tomography shows symmetric hypodensities in both globi pallidi (A). Axial T2-weighted magnetic resonance image shows bilateral symmetric hyperintensity within the globi pallidi (B). There is also atrophy or hypoplasia of the Sylvian cortex (A, B).
* Communications should be addressed to: Dr. Sedat Is¸ikay; Department of Pediatric Neurology; Gaziantep Children’s Hospital; 27500; S¸ehitkamil; Gaziantep, Turkey. E-mail address: [email protected] 0887-8994/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2013.11.008
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S. Is¸ikay et al. / Pediatric Neurology 50 (2014) 435e436
distinctive for signal changes of globi pallidi. On the diffusion-weighted images, the globi pallidi lesions were markedly hyperintense as the appearance of acute infarct. Organic acid analysis of urine revealed high levels of methylmalonic acid (5640 mmol/mmol creatinine). Considering these findings, the patient was diagnosed with methylmalonic aciduria. He was put on a protein-restricted diet, L-carnitine, and vitamin B12 treatment. After approximately 6 months’ follow-up, no change in his clinical status has been observed. Patients with methylmalonic aciduria usually become symptomatic during the first year of life with lethargy, recurrent vomiting, feeding difficulties, dehydration, and severe metabolic acidosis, as in our patient.1 Cranial imaging can reveal symmetric involvement of basal ganglia, cerebral atrophy, and delayed myelination. The basal ganglia changes, which appear as low density on computed tomography scan and hyperintense on T2weighted magnetic resonance images, occur predominantly in the globi pallidi. Our patient had bilaterally symmetrical signal changes in the globi pallidi.
Hyperintense signal changes of globi pallidi were more obvious on diffusion-weighted images than on T2weighted images. Although basal ganglia signal changes have radiological importance in the diagnosis of methylmalonic aciduria, this pattern can also be observed in conditions such as methanol poisoning, carbon monoxide intoxication, or anoxic stroke and hypoplasia. Differential diagnosis of anterior cerebral atrophy also includes propionic acidemia, pyruvate dehydrogenase deficiency, kernicterus, and carbon monoxide poisoning.1,2 In conclusion, methylmalonic aciduria should be considered in infants with neurological symptoms and basal ganglia abnormalities. References 1. Tanpaiboon P. Methylmalonic acidemia (MMA). Mol Genet Metab. 2005;85:2-6. 2. Radmanesh A, Zaman T, Ghanaati H, Molaei S, Robertson RL, Zamani AA. Methylmalonic acidemia: brain imaging findings in 52 children and a review of the literature. Pediatr Radiol. 2008;38: 1054-1061.
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Visual Diagnosis
Imaging Findings Associated With Methylmalonic Aciduria Sedat Is¸ikay MD a, *, Levent Temel MD b, Mehmet Keskin MD c a
Department of Pediatric Neurology, Gaziantep Children’s Hospital, Gaziantep, Turkey Department of Pediatrics, Gaziantep Children’s Hospital, Gaziantep, Turkey c Department of Pediatric Endocrinology and Metabolisms, Gaziantep University, Gaziantep, Turkey b
The conversion of methylmalonic acid to succinic acid requires both an apoenzyme (methylmalonyl CoA mutase) and a coenzyme (adenosylcobalamin). Deficiency of either entity results in accumulation of methylmalonic acid derivatives in physiologic fluids. The basal ganglia, predominantly globi pallidi, are particularly sensitive to metabolic dysfunction and are thus the main targets for brain injury in this condition. A 7-month-old boy was admitted with a 2-day history of vomiting and lethargy. Clinical examinations revealed
tachypnea, tachycardia, lethargy, hypotonia, dehydration, and failure to thrive. Blood gas analysis showed severe metabolic acidosis with low pH (7.01) and bicarbonate (7.5 mmol/L). Serum ammonia was 214 mg/dL (29-70 mg/dL); serum lactate was 25 mg/dL (5-22 mg/dL). Computed tomography showed symmetrical hypodensities in the globi pallidi and periventricular areas along with bilateral frontal atrophy and Sylvian hypoplasia. T2-weighted magnetic resonance images revealed symmetric high signals in both globi pallidi (Figure). T1-weighted images were not
FIGURE. Axial computed tomography shows symmetric hypodensities in both globi pallidi (A). Axial T2-weighted magnetic resonance image shows bilateral symmetric hyperintensity within the globi pallidi (B). There is also atrophy or hypoplasia of the Sylvian cortex (A, B).
* Communications should be addressed to: Dr. Sedat Is¸ikay; Department of Pediatric Neurology; Gaziantep Children’s Hospital; 27500; S¸ehitkamil; Gaziantep, Turkey. E-mail address: [email protected] 0887-8994/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2013.11.008
436
S. Is¸ikay et al. / Pediatric Neurology 50 (2014) 435e436
distinctive for signal changes of globi pallidi. On the diffusion-weighted images, the globi pallidi lesions were markedly hyperintense as the appearance of acute infarct. Organic acid analysis of urine revealed high levels of methylmalonic acid (5640 mmol/mmol creatinine). Considering these findings, the patient was diagnosed with methylmalonic aciduria. He was put on a protein-restricted diet, L-carnitine, and vitamin B12 treatment. After approximately 6 months’ follow-up, no change in his clinical status has been observed. Patients with methylmalonic aciduria usually become symptomatic during the first year of life with lethargy, recurrent vomiting, feeding difficulties, dehydration, and severe metabolic acidosis, as in our patient.1 Cranial imaging can reveal symmetric involvement of basal ganglia, cerebral atrophy, and delayed myelination. The basal ganglia changes, which appear as low density on computed tomography scan and hyperintense on T2weighted magnetic resonance images, occur predominantly in the globi pallidi. Our patient had bilaterally symmetrical signal changes in the globi pallidi.
Hyperintense signal changes of globi pallidi were more obvious on diffusion-weighted images than on T2weighted images. Although basal ganglia signal changes have radiological importance in the diagnosis of methylmalonic aciduria, this pattern can also be observed in conditions such as methanol poisoning, carbon monoxide intoxication, or anoxic stroke and hypoplasia. Differential diagnosis of anterior cerebral atrophy also includes propionic acidemia, pyruvate dehydrogenase deficiency, kernicterus, and carbon monoxide poisoning.1,2 In conclusion, methylmalonic aciduria should be considered in infants with neurological symptoms and basal ganglia abnormalities. References 1. Tanpaiboon P. Methylmalonic acidemia (MMA). Mol Genet Metab. 2005;85:2-6. 2. Radmanesh A, Zaman T, Ghanaati H, Molaei S, Robertson RL, Zamani AA. Methylmalonic acidemia: brain imaging findings in 52 children and a review of the literature. Pediatr Radiol. 2008;38: 1054-1061.