Cranial Magnetic Resonance Imaging Findings in Hypotonic Infants with Cobalamin Deficiency and Combined Methylmalonic Aciduria and Homocystinuria

Abstract

Vitamin B12 begins to accumulate in infants within the first six months while mothers often remain asymptomatic and infantile vitamin B12 deficiency may not be noticed until the onset of neurological effects. In infants with Cbl deficiency, long-term exposure to elevated methylmalonic acid and homocysteine (MMA-HC) may have toxic effects on the central nervous system. The aim of this study was to evaluate cranial magnetic resonance (MRI) findings of 23 hypotonic infants that were followed up with a diagnosis of nutritional Cbl deficiency and combined MMA-HC. Of the 78 infants that presented with hypotonicity, 23 (29.4%) infants were detected with vitamin B12 deficiency. Elevated MMA-HC levels were detected in all patients (100%). Cranial MRI showed cortical atrophy in 6 (26.0%)-large sylvian fissures in 7 (30.4%)-ventricular dilatation in 5 (21.7%)-corpuscallosal thinning in 6 (26.0%)-delayed myelination in 3 (13%), and normal in 8 (34.7%) infants.Infants detected with corpus callosal thinning and cortical atrophy on MRI. Vitamin B12 deficiency is a treatable condition, it should be suspected in infants presenting with hypotonicity. Neuroradiological findings should be considered in the diagnosis of such patients. İnfantile nutritional vitamin B12 deficiency, which can be a source of persistent neurological deficits during the long term, should be treated to allow the patient to allow healthy neuro-development for infants. Maternal and fetal vitamin B12 levels should be assessed during the third trimester of pregnancy to prevent long-term exposure to infantile vitamin B12 deficiency.

Zusammenfassung

Vitamin B12 beginnt sich bei Säuglingen innerhalb der ersten sechs Monate anzureichern, während die Mütter oft asymptomatisch bleiben und ein infantiler Vitamin-B12-Mangel möglicherweise erst beim Auftreten neurologischer Effekte bemerkt wird.Bei Säuglingen mit Cbl-Mangel kann eine langfristige Exposition gegenüber erhöhter Methylmalonsäure und Homocystein toxische Auswirkungen auf das zentrale Nervensystem haben. Ziel dieser Studie war es, die kranialen Magnetresonanz-Befunde von 23 hypotonen Säuglingen auszuwerten, die mit der Diagnose eines ernährungsbedingten Cbl-Mangels und kombiniertem MMS-HC nachuntersucht wurden. Von den 78 Säuglingen, die sich mit Hypotonie vorstellten, wurde bei 23 (29,4%) Säuglingen ein Vitamin B12-Mangel festgestellt. Erhöhte MMS-HC-Werte wurden bei allen Patienten (100%) nachgewiesen. Die kraniale MRT zeigte eine kortikale Atrophie bei 6 (26,0%)-vergrößerte Sylvische Fissuren bei 7 (30,4%)-eine ventrikuläre Dilatation bei 5 (21,7%)-eine korpus kallosale Ausdünnung bei 6 (26,0%)-eine verzögerte Myelinisierung bei 3 (13%)-normale Werte bei 8 (34,7%) Säuglingen. Bei denen im MRT eine Ausdünnung des corpus callosums und eine kortikale Atrophie festgestellt wurde. Vitamin B12-Mangel ist eine behandelbare Erkrankung, die bei Säuglingen mit Hypotonie. Neuroradiologische Befunde sollten bei der Diagnose solcher Patienten berücksichtigt werden. Infantiler ernährungsbedingter Vitamin B12-Mangel, der langfristig eine Ursache für persistierende neurologische Defizite sein kann, sollte behandelt werden, um dem Patienten/Säugling eine gesunde Neuro-Entwicklungzu ermöglichen. Der mütterliche und fetale Vitamin B12 sollte während des dritten Trimesters der Schwangerschaft bestimmt werden, um eine langfristige Gefährdung durch einen infantilen Vitamin B12-Mangel zu verhindern

Key words

Cranial magnetic resonance imaging - hypotonic infants - methylmalonicaciduria - homocystinuria - cobalamin

Schlüsselwörter

Kraniale Magnetresonanztomographie - hypotonische Säuglinge - Methylmalonicacidurie - Homocystinurie - Cobalamin

• References

• 1 Baumgartner ER, Wick H, Maurer R. et al. Congenitaldefect in intracellular cobalamin metabolism resulting in homocystinuria and methylmalonic aciduria. Helv Paediat Acta 1979; 34: 465-482
• 2 Biancheri R, Cerone R, Schiaffino MC. et al. Cobalamin (Cbl) C/D deficiency: clinical, neurophysiological and neuroradiological findings in 14 cases. Neuropediatrics 2001; 32: 14-22
• 3 Codazzi D, Sala F, Parini R. et al. Coma and respiratory failure in a child with severe vitamin B 12 deficiency. Pediatr Crit Care Med 2005; 6: 483-485
• 4 Çoban S, Yılmaz Keskin E, İğde M. Association between Maternal and Infantile Markers of Cobalamin Status During the First Month Post-Delivery. Indian J Pediatr 2018; 85: 517-522
• 5 Engelbrecht V, Rassek M, Huismann J. et al. MR and proton MR spectroscopy of the brain in hyperhomocysteinemia caused by methylentetrahydrofolate reductase deficiency. AJNR 1997; 18: 536-539
• 6 Greitz D, Greitz T. The pathogenesis and hemodynamics of hydrocephalus. Int J Neuroradiol 1997; 3: 367-375
• 7 Healton EB, Savage DG, Brust JCM. et al. Neurologic aspects of cobalamin deficieny. Medicine (Baltimore) 1995; 70: 229-245
• 8 Incecik F, Herguner MO, Altunbasak S. et al. Neurologic findings of nutritional vitamin B12 deficiency in children. Turk J Pediatr 2010; 52: 17-21
• 9 Katar S, Ozbek MN, Yaramis A. et al. Nutritional megaloblastic anemia in young Turkish children is associated with vitamin B-12 deficiency and psychomotor retardation. J Pediatr Hematol Oncol 2006; 28: 559-562
• 10 Koc A, Kocyigit A, Soran M. High frequency of maternal vitamin B12 deficiency as an importantcause of infantile vitamin B12 deficiency in Sanliurfa province of Turkey. Eur J Nutr 2006; 45: 291-2977
• 11 Lindblad B, Lindblad BS, Olin P. et al. Methylmalonicacidemia – A disorder associated with acidosis hyperglycinemia and hyperlactatemia. Acta Paediatr. Scand. 1968; 57: 417–424
• 12 Lövblad K, Ramelli G, Remonda L. Retardation of myelination due to dietary vitamin B12 deficiency: cranial MRI findings. Pediatr Radiol 1997; 27: 155-158
• 13 Yue NC. et al. Sulcal, ventricular, and white matter changes at MR imaging in the aging brain: Data from the Cardiovascular Health Study. Radiology 1997; 202: 33-39
• 14 Rossi A, Cerone R, Biancheri R. et al. Early-onset combined methylmalonic aciduria and homocystinuria: neuroradiologic findings. AJNR Am J Neuroradiol 2001; 22: 554-563
• 15 Serin HM, Arslan EA. Neurological symptoms of vitamin B12 deficiency: analysis of pediatric patients. Acta Clin Croat 2019; 58: 295-302
• 16 Snow CF. Laboratory Diagnosis of Vitamin B12 and Folate Deficiency. Arch Intern Med 1999; 28: 1289-1298
• 17 Stollhoff K, Schulte FJ. Vitamin B12 and brain development. Eur J Pediatr 1987; 146: 201-205
• 18 Surtees R, Leonard J, Austin S. Association of demyelination with deficiency of cerebrospinal-fluid S-adenosylmethionine in inborn errors of methyl-transfer pathway. Lancet 1991; 338: 1550-1554
• 19 Taskesen M, Yaramis A, Pirinccioglu AG. et al. Cranial magnetic resonance imaging findings of nutritional vitamin B12 deficiency in 15 hypotonic infants. Eur J Paediatr Neurol 2012; 16: 266-270
• 20 VonSchenck U, Gotze CB, Koletzko B. Persistence of neurological damage induced by dietary vitamin B12 deficiency in infancy. ArchDis Child 1997; 77: 137-139
• 21 Wighton MC, Manson MB, Speed I. Brain damage in infancy and dietary vitamin B12 deficiency. Med J Aust 1979; 2: 1-3
• 22 Yang L, Guo B, Li X. et al. Brain MRI features of methylmalonic acidemia in children: the relationship between neuropsychological scores and MRI findings. Scientific Report 2020; 4: 10 1309
• 23 von Schenck U, Bender-Gotze C, Koletzko B. Persistence of neurological damage induced by dietary vitamin B-12 deficiency in infancy. Arch Dis Ghild 1997; 77: 137-139
• 24 Rasmussen SA, Fernhoff PM, Scanlon KS. Vitamin B12 deficiency in children and adolescents. J Pediatr 2001; 138: 10-17
• 25 Ekici F, Tekbas G, Hattapoğlu S. et al. Brain MRI and MR Spectroscopy Findings in Children with Nutritional Vitamin B12 Deficiency. Clin Neuroradiol 2016; 26: 215-220
• 26 Kocaoglu C, Akin F, Caksen H. et al. Cerebral atrophy in a vitamin B12-deficient infant of a vegetarian mother. J Health Popul Nutr. 2014