Barkovich, AJ

Magalhães, Z

Rocha, JF

Soares-Fernandes, JP

English

Institutional repository of Hospital de Braga

Brain Diffusion-Weighted and Diffusion Tensor ImagingFindings in an Infant with Biotinidase DeficiencyA previously healthy 7-week-old male infant was admitted because ofclonic movements of the upper limbs. Findings of a neurologic exami-nation were normal. His psychomotor development was appropriate forhis age. Brain MR imaging showed supra- and infratentorial white mattersignal-intensity abnormality, suggestive of edema, with frontal predom-inance and peripheral U-fiber involvement. Myelination was slightly di-minished in the posterior limbs of the internal capsules, also compatiblewith edema. The corpus callosum was spared. Deep gray matter struc-tures had a normal appearance. No malformations were detected. Diffu-sion-weighted imaging (DWI, b  1000 s/mm2) and diffusion tensorimaging revealed symmetric moderately reduced diffusion with abnor-mally increased fractional anisotropy in the centra semiovalia and peri-rolandic white matter (Fig 1). MR spectroscopy (regions of interest po-sitioned at the left centrum semiovale and basal nuclei; TE  30 and 135ms; not shown) showed a lactate doublet at 1.33 ppm.Laboratory investigation demonstrated elevated plasma lactate (19.6mg/dL; reference range, 3.1–12.0 mg/dL) and urinary 3-hydroxy-isovaleric acid (1786 mol/mmol of creatine; reference range, 10 – 67mol/mmol of creatine) levels and absent plasma biotinidase activity.Biotin supplementation (5 mg per day, by mouth) was started. Nofurther seizures were noted. A follow-up brain MR imaging at 3months of age showed normalization of the white matter signal in-tensity. The child was neurologically and developmentally normal at10 months of age.Biotinidase converts biotin, an essential water-soluble vitamin, intoits bioavailable form. Biotinidase deficiency is a rare autosomal recessivedisorder, with an estimated prevalence of approximately 1:60,000 neo-nates,1 causing multiple carboxylase deficiencies (for which biotin is acoenzyme) and leading to energy depletion, due to impaired catabolismof several branched chain amino acids, gluconeogenesis, and fatty acidsynthesis.2 Neurologic involvement in biotinidase deficiency manifests inthe first few years of life, with seizures, optic atrophy, and sensorineuralhearing loss.3 Conventional MR imaging and MR spectroscopy featuresreflect the known pathophysiologic mechanisms in this deficiency. Pro-longed T1 and T2 of the white matter may be explained by diffuse inter-stitial edema. The lactate peak on MR spectroscopy is related to the con-version to anaerobic metabolism.4,5A previous description of a patient with biotinidase deficiency5 dem-onstrated markedly reduced diffusion in the brain stem, middle cerebel-lar peduncles, splenium of the corpus callosum, posterior limbs of theinternal capsules, corona radiata, and parieto-occipital gray matter. Inour patient, a different pattern was observed, with moderately reduceddiffusion and increased fractional anisotropy in the perirolandic whitematter and centra semiovalia. This could be due to accelerated myelina-tion of those areas, induced by the repeated neuronal electric activity ofthe seizures, as was previously reported in children with Stürge-Webersyndrome6 and in experimental studies in mice.7 Vacuolating myeli-nopathy and myelin edema were previously described in neuropatho-logic studies in biotinidase deficiency.3 However, in our patient, theseseem an unlikely explanation for the imaging findings because intramy-elinic edema usually causes markedly reduced water diffusion and de-creased fractional anisotropy in white matter.8References1. Wolf B. Worldwide survey of neonatal screening of biotinidase deficiency.J Inherit Metab Dis 1991;14:923–372. Wolf B. Disorders of biotin metabolism. In: Scriver CR, Beaudet AL, Valle D,et al, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. NewYork: McGraw-Hill; 2001:3935– 623. van der Knaap MS, Valk J. Multiple carboxylase deficiency. In: Magnetic Reso-nance of Myelination and Myelin Disorders. 3rd ed. Berlin: Springer-Verlag;2005:248 –514. Schürmann M, Engelbrecht V, Lohmeier K, et al. Cerebral metabolic changes inbiotinidase deficiency. J Inherit Metab Dis 1997;20:755– 605. Desai S, Ganesan K, Hegde A. Biotinidase deficiency: a reversible metabolicencephalopathy—neuroimaging and MR spectroscopic findings in a series offour patients. Pediatr Radiol 2008;38:848 –566. Jacoby CG, Yuh WT, Afifi AK, et al. Accelerated myelination in early Stürge-Weber syndrome demonstrated by MR imaging. J Comput Assist Tomogr1987;11:226 –317. Demerens C, Stankoff B, Logar M, et al. Induction of myelination in the centralnervous system by electrical activity. Proc Natl Acad Sci U S A 1996;93:9887–928. Patay Z. Diffusion-weighted MR imaging in leukodystrophies. Eur Radiol2005;15:2284 –303J.P. Soares-FernandesZ. MagalhãesJ.F. RochaDepartment of NeuroradiologyHospital de S. MarcosBraga, PortugalA.J. BarkovichDepartment of Radiology and Biomedical ImagingUniversity of CaliforniaSan Francisco, CalifDOI 10.3174/ajnr.A1703Fig 1. A, Apparent diffusion coefficient (ADC) map demon-strates decreased signal intensity in the perirolandic whitematter and centrum semiovalia. ADC value, measured in theleft centra semiovale at the MR imaging workstation (Syngo;Siemens, Erlangen, Germany) is reduced (0.87  103 mm2/s); in an age-matched control (not shown), ADC measured inthe same location was 1.4  103 mm2/s. Note alsoincreased water diffusion in the remaining hemispheric whitematter, with frontal predominance, suggestive of interstitialedema. B, Fractional anisotropy map shows increased anisot-ropy in the perirolandic white matter and centra semiovalia.E128 Letters  AJNR 30  Oct 2009  www.ajnr.org

Brain diffusion-weighted and diffusion tensor imaging findings in an infant with biotinidase deficiency

Repositório Comum

Brain Diffusion-Weighted and Diffusion Tensor ImagingFindings in an Infant with Biotinidase DeficiencyA previously healthy 7-week-old male infant was admitted because ofclonic movements of the upper limbs. Findings of a neurologic exami-nationwere normal. His psychomotor developmentwas appropriate forhis age.BrainMRimaging showedsupra- and infratentorialwhitemattersignal-intensity abnormality, suggestive of edema, with frontal predom-inance and peripheral U-fiber involvement. Myelination was slightly di-minished in the posterior limbs of the internal capsules, also compatiblewith edema. The corpus callosum was spared. Deep gray matter struc-tures had a normal appearance. Nomalformationswere detected. Diffu-sion-weighted imaging (DWI, b  1000 s/mm2) and diffusion tensorimaging revealed symmetric moderately reduced diffusion with abnor-mally increased fractional anisotropy in the centra semiovalia and peri-rolandic white matter (Fig 1). MR spectroscopy (regions of interest po-sitioned at the left centrum semiovale and basal nuclei; TE 30 and 135ms; not shown) showed a lactate doublet at 1.33 ppm.Laboratory investigationdemonstrated elevated plasma lactate (19.6mg/dL; reference range, 3.1–12.0 mg/dL) and urinary 3-hydroxy-isovaleric acid (1786mol/mmol of creatine; reference range, 10–67mol/mmol of creatine) levels and absent plasma biotinidase activity.Biotin supplementation (5 mg per day, by mouth) was started. Nofurther seizures were noted. A follow-up brain MR imaging at 3months of age showed normalization of the white matter signal in-tensity. The child was neurologically and developmentally normal at10 months of age.Biotinidase converts biotin, an essential water-soluble vitamin, intoits bioavailable form. Biotinidase deficiency is a rare autosomal recessivedisorder, with an estimated prevalence of approximately 1:60,000 neo-nates,1 causing multiple carboxylase deficiencies (for which biotin is acoenzyme) and leading to energy depletion, due to impaired catabolismof several branched chain amino acids, gluconeogenesis, and fatty acidsynthesis.2Neurologic involvement inbiotinidasedeficiencymanifests inthe first few years of life, with seizures, optic atrophy, and sensorineuralhearing loss.3 Conventional MR imaging andMR spectroscopy featuresreflect the known pathophysiologic mechanisms in this deficiency. Pro-longed T1 and T2 of the white matter may be explained by diffuse inter-stitial edema. The lactate peak onMR spectroscopy is related to the con-version to anaerobic metabolism.4,5A previous description of a patient with biotinidase deficiency5 dem-onstratedmarkedly reduced diffusion in the brain stem,middle cerebel-lar peduncles, splenium of the corpus callosum, posterior limbs of theinternal capsules, corona radiata, and parieto-occipital gray matter. Inour patient, a different pattern was observed, with moderately reduceddiffusion and increased fractional anisotropy in the perirolandic whitematter and centra semiovalia. This could be due to acceleratedmyelina-tion of those areas, induced by the repeated neuronal electric activity ofthe seizures, as was previously reported in children with Stu¨rge-Webersyndrome6 and in experimental studies in mice.7 Vacuolating myeli-nopathy and myelin edema were previously described in neuropatho-logic studies in biotinidase deficiency.3 However, in our patient, theseseem an unlikely explanation for the imaging findings because intramy-elinic edema usually causes markedly reduced water diffusion and de-creased fractional anisotropy in white matter.8References1. Wolf B. Worldwide survey of neonatal screening of biotinidase deficiency.J Inherit Metab Dis 1991;14:923–372. Wolf B. Disorders of biotin metabolism. In: Scriver CR, Beaudet AL, Valle D,et al, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. NewYork: McGraw-Hill; 2001:3935–623. van der Knaap MS, Valk J.Multiple carboxylase deficiency. In:Magnetic Reso-nance of Myelination and Myelin Disorders. 3rd ed. Berlin: Springer-Verlag;2005:248–514. Schu¨rmannM,EngelbrechtV, LohmeierK, et al.Cerebralmetabolic changes inbiotinidase deficiency. J Inherit Metab Dis 1997;20:755–605. Desai S, Ganesan K, Hegde A. Biotinidase deficiency: a reversible metabolicencephalopathy—neuroimaging andMR spectroscopic findings in a series offour patients. Pediatr Radiol 2008;38:848–566. Jacoby CG, Yuh WT, Afifi AK, et al. Accelerated myelination in early Stu¨rge-Weber syndrome demonstrated by MR imaging. J Comput Assist Tomogr1987;11:226–317. DemerensC, Stankoff B, LogarM, et al. Induction ofmyelination in the centralnervous systemby electrical activity. Proc Natl Acad Sci U S A 1996;93:9887–928. Patay Z. Diffusion-weighted MR imaging in leukodystrophies. Eur Radiol2005;15:2284–303J.P. Soares-FernandesZ. Magalha˜esJ.F. RochaDepartment of NeuroradiologyHospital de S. MarcosBraga, PortugalA.J. BarkovichDepartment of Radiology and Biomedical ImagingUniversity of CaliforniaSan Francisco, CalifDOI 10.3174/ajnr.A1703Fig 1. A, Apparent diffusion coefficient (ADC) map demon-strates decreased signal intensity in the perirolandic whitematter and centrum semiovalia. ADC value, measured in theleft centra semiovale at the MR imaging workstation (Syngo;Siemens, Erlangen, Germany) is reduced (0.87  103 mm2/s); in an age-matched control (not shown), ADC measured inthe same location was 1.4  103 mm2/s. Note alsoincreased water diffusion in the remaining hemispheric whitematter, with frontal predominance, suggestive of interstitialedema. B, Fractional anisotropy map shows increased anisot-ropy in the perirolandic white matter and centra semiovalia.E128 Letters  AJNR 30  Oct 2009  www.ajnr.org

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Brain diffusion-weighted and diffusion tensor imaging findings in an infant with biotinidase deficiency

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