Undiagnosed Metachromatic Leukodystrophy Presenting as Severe Gastrointestinal Bleeding and Cholestasis from Hemobilia.

Metachromatic leukodystrophy (MLD) is a neurodegenerative disorder caused by the accumulation of lipids called sulfatides throughout the nervous system. Sulfatides can also collect in other organs throughout the body including the gallbladder where they form polyps. Gallbladder polyps rarely have been found to bleed in patients with known MLD, presumably due to polyp shearing. Here we present a case of a child with autism presenting with severe gastrointestinal bleeding and direct hyperbilirubinemia, requiring significant resuscitation and biliary drain placement to tamponade ongoing bleeding. Subsequent neurologic and genetic investigation led to the diagnosis of MLD, with laparoscopic cholecystectomy revealing extensive, elongated gallbladder polyps. Clinicians who care for patients with MLD, including gastroenterologists who manage their progressive oropharyngeal dysphagia, should be aware of the risk for this life-threatening complication. Moreover, pediatric gastroenterologists and hepatologists should maintain a high index of suspicion for MLD in new patients presenting with developmental regression and gastrointestinal bleeding.

An Indirect Action Contributes to C-Fos Induction in Paraventricular Hypothalamic Nucleus by Neuropeptide Y.

Neuropeptide Y (NPY) is a well-established orexigenic peptide and hypothalamic paraventricular nucleus (PVH) is one major brain site that mediates the orexigenic action of NPY. NPY induces abundant expression of C-Fos, an indicator for neuronal activation, in the PVH, which has been used extensively to examine the underlying NPY orexigenic neural pathways. However, PVH C-Fos induction is in discordance with the abundant expression of NPY receptors, a group of inhibitory Gi protein coupled receptors in the PVH, and with the overall role of PVH neurons in feeding inhibition, suggesting a mechanism of indirect action. Here we showed that the ability of NPY on C-Fos induction in the PVH was blunted in conditions of insulin deficiency and fasting, a condition associated with a high level of NPY and a low level of insulin. Moreover, insulin insufficiency blunted C-Fos induction in the PVH by fasting-induced re-feeding, and insulin and NPY induced c-Fos induction in the same group of PVH neurons. Finally, NPY produced normal C-Fos induction in the PVH with disruption of GABA-A receptors. Thus, our results revealed that PVH C-Fos induction by NPY is mediated by an indirect action, which is at least partially mediated by insulin action, but not GABA-A receptors.