A newborn with liver failure and coma Teaching NeuroImages Neurology Resident and Fellow Section © 2015 American Academy of Neurology 1

Vignette A female newborn showed hypoglycaemia, cholestatic jaundice, hypertransaminasemia, liver failure. Galactose-free diet was started but she rapidly became comatose. Brain MRI with spectroscopy documented diffuse edema (Fig. 1A-D) and galactitol peak (Fig. 2). Despite antiedema therapy, she died at 21 days for cerebral herniation. Martinelli, et al © 2015 American Academy of Neurology

Imaging Martinelli, et al A A B B C C Figure 1: Conventional Magnetic Resonance Imaging (MRI) and Diffusion Weighted Imaging (DWI) with apparent diffusion coefficient (ADC) map Sagittal (A) and axial (B) Turbo-Spin-Echo T2Weighted-Images, DWI (C), ADC (D). Brain and cerebellum appear diffusely swollen with reduced gray/white matter differentiation (B). Massive edema causes cerebellar tonsils to descend into the foramen magnum (A). DWI and ADC maps show large posterior areas of restricted diffusion consistent with cytotoxic edema (C, D). Martinelli, et al © 2015 American Academy of Neurology

Imaging Martinelli, et al A A B B C C Figure 2: Magnetic Resonance (MR) Spectroscopy Single voxel short Time of Echo (TE 30ms) localized into right parietal white matter. LC-Model fitted MR spectrum showing presence of both galactitol and lactate. The in vivo concentrations of galactitol (prominent peak at 3.7 ppm) and lactate obtained from MR spectroscopy were 21.3 ±1.0 and 6.4 ±.6 mmol/Kg respectively. Martinelli, et al © 2015 American Academy of Neurology

Too much sugar in the brain: galactitol peak and fatal cerebral edema in classic galactosemia Classic galactosemia due to GALT (Galactose-1-Phosphate Uridyltransferase) deficiency (MIM #230400), the most frequent inborn galactose metabolism disorder, presents with hepatopathy, cataracts and occasionally intracranial hypertension. Symptoms generally resolve with galactose-free diet. Fatal cerebral edema is exceptional [1] and might be related to massive galactitol accumulation, an osmotic metabolite impermeable to membranes, synthetized by galactose through alternative pathways [2]. REFERENCES 1.Perelmuter B, Goodman SI, McCabe ER. Galactosaemia with fatal cerebral oedema. J Inherit Metab Dis 1989;12:489-490. 2.Berry GT, Hunter JV, Wang Z, et al. In vivo evidence of brain galactitol accumulation in an infant with galactosemia and encephalopathy. J Pediatr 2001;138:260-262. Martinelli, et al © 2015 American Academy of Neurology