Contribution of the diffusion-weighted MRI in the diagnosis and follow-up of encephalopathy caused by maple syrup urine disease in a full-term newborn

Abstract

ContribuiÇÃo da SeQÜÊnCia difuSÃo da Mr no diagnÓStiCo e aCoMpanhaMento da enCefalopatia por doenÇa da urina eMMaple syrup urine disease (MSUD) or leucinosis is caused by a deficiency of the catalytic components of the α-ketoacid-dehydrogenase complex, which is responsible for the catabolism of branched-chain amino acids (leucine, isoleucine, and valine) 1,2 . It is an inherited genetic disease with an autosomal recessive pattern affecting approximately 1 out of 120,000-500,000 infants worldwide 3,4 . Diagnosis is made clinically based on the peculiar maple syrup odor or sugar burnt of the urine, encephalopathy, increased levels of branched-chain amino acids in the plasma and urine, and the presence of α-hydroxyacid and branched-chain α-ketoacids in urine. The presence of plasma L-alloisoleucine and urinary α-hydroxyisovalerate are pathognomonic for MSUD 2 . According to the literature, five forms of MSUD have been described: classic, intermediate, intermittent, thiamine-responsive, and dihydrolipoyl dehydrogenase-deficient. The commonest and severest form of the disease is the classic type, which is characterized by a neonatal onset of encephalopathy 2 . Magnetic resonance imaging (MRI) studies in the acute phase of classic MSUD are characterized by diffuse edema corresponding to both myelinated and unmyelinated areas of the brain [3][4][5][6] . The purpose of this case report is to show conventional MRI and diffusion-weighted imaging (DWI) findings of the different evolutionary phases in MSUD of a newborn that evolved with brain white matter lesions. CaSeA full-term male infant born from an uneventful pregnancy and delivery, with a birth weight of 3.245g and Apgar scores of 9/10 (at 1 and 5 min, respectively), was hospitalized because of sucking difficulties, weak cry, and lethargy. At 10 days of life, the baby had episodes of seizures, bradycardia, and apnea, leading to coma. Biochemical examinations showed hypoglycemia and metabolic ketoacidosis. Brain MRI at 10 days of life showed hypersignal lesions on DWI and corresponding hyposignals on ADC maps throughout the white matter of the brainstem, cerebella and internal capsules (Fig 1).At 20 days of life the clinical condition of the baby became critical and maple syrup odor or sugar burnt was noted in the urine. A repeat MRI at this time showed increasing myelinating white matter lesions and new hypersignal lesions on T2-weighted sequences and hyposignal on the diffusion-weighted images located in the unmyelinated white matter of the frontal, parietal and temporal lobes (Fig 2).At 25 At 8 months of age, a follow-up MRI was performed that showed persisting white matter lesions in the frontal, parietal and temporal lobes with associated hypersignal on DWI and hy-

Brain Branched-Chain Amino Acids in Maple Syrup Urine Disease: Implications for Neurological Disorders

“…As a consequence, NAA deficiency in MSUD may result in defective myelination. Indeed, myelination differences are frequently observed in MSUD patients on magnetic resonance imaging (MRI) scans [ 56 , 57 , 58 , 59 , 60 , 61 ]. Additional evidence from histological and electrophysiological data also demonstrated myelin destruction and axonal degeneration in a MSUD case [ 62 ].…”

Cerebral Edema in Maple Syrup Urine Disease Despite Newborn Screening Diagnosis and Early Initiation of Treatment

“…In the reported cases, the restricted diffusion predominantly in the areas of myelinated white matter was reversible after treatment, whereas the methyl resonance of BCAAs shown on proton MR spectroscopy persisted even after the acute metabolic crisis had been controlled and the plasma leucine level had reached normal (Sener 2007;Ferraz-Filho et al 2009). …”

Evaluation of Neonatal Acute Metabolic Crisis in Maple Syrup Urine Disease with MR Diffusion and MR Spectroscopy: Case Series and Review of the Literature

“…These subsequent episodes are usually associated with anemia and urinary tract infection. 14 MRI brain examinations in older patients with MSUD exacerbation reveal mixed findings. Though areas commonly involved in neonatal exacerbation could still be involved in adult cases, they are assumed to develop relative tolerance to successive neurotoxicity with regional shift of neurotoxic effect.…”

“…At about 1-week, pseudonormalization of ADC values is noted. 12 14 Some residual neuroparenchymal damage with atrophic changes in the form of prominent ventricles and sulcal spaces is noted on follow-up imaging; however, typical gliotic changes do not occur in MSUD patients. Cranial transfontanelle ultrasonographic (HUS) examination reveals bilateral increased echogenicity in the affected areas.…”