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

**Background** Metachromatic leukodystrophy (MLD) is a rare autosomal recessive neurodegenerative disorder caused by arylsulfatase A (ARSA) deficiency, leading to sulfatide accumulation in the nervous system and other organs, including the gallbladder where polyps can form. Gallbladder polyps in MLD can rarely cause hemobilia, but no prior case has reported a new diagnosis of MLD presenting with massive gastrointestinal bleeding in a previously healthy child. This case highlights the need for awareness among gastroenterologists and hepatologists.

**Methods** This is a single case report of a 5-year-old male with autism spectrum disorder who presented to the emergency department with acute hematemesis and melena. The report details the clinical presentation, laboratory findings, imaging studies, interventions, and subsequent diagnostic workup leading to the diagnosis of MLD. The patient underwent multiple procedures including esophagogastroduodenoscopy (EGD), magnetic resonance cholangiopancreatography (MRCP), angiography, percutaneous transhepatic cholangiogram (PTC) with biliary drain placement, and eventually laparotomy with cholecystectomy. Genetic testing and urine sulfatide analysis confirmed MLD.

**Key Results** - Initial labs: hemoglobin 6.9 g/dL, aspartate aminotransferase 310 U/L, alanine aminotransferase 510 U/L, total bilirubin 3.6 mg/dL (direct 2.7 mg/dL), gamma-glutamyl transferase 325 U/L, prothrombin time 15.1 seconds, INR 1.2. - Abdominal ultrasound showed gallbladder wall thickening to 6.5 mm, sludge, and common bile duct dilation to 4 mm with sludge. - MRCP suggested a possible type 4B choledochal cyst with cystic dilatation of extrahepatic common hepatic duct up to 10 mm. - Angiography showed hyperemia at the tip of the gallbladder but no active bleeding source. - PTC with internal/external biliary drain was placed; output turned from bloody to bilious over 72 hours. - The patient required 6 units packed red blood cells, 2 units fresh frozen plasma, and 1 unit of platelets. - Bilirubin and transaminases improved rapidly after drain placement; hemoglobin stabilized by hospital day 5. - MRI brain showed classic "Tigroid" or "Leopard Skin" pattern in periventricular white matter consistent with MLD. - Genetic testing revealed two heterozygous variants in ARSA: pathogenic p.Glu309Lys and variant of unknown significance p.Val388Phe; urine sulfatides were positive. - Cholecystectomy on hospital day 15 revealed thickened gallbladder wall with long tentacle-like growths and old blood; histology showed columnar mucinous papillary proliferation, goblet cells (intestinal metaplasia), and increased histiocytes; electron microscopy showed lysosomal inclusions with herringbone and prismatic patterns. - Intraoperative cholangiogram showed normal CBD but persistent CHD dilation; the possible choledochal cyst was not resected due to poor prognosis. - Repeat ultrasound 2 months post-discharge showed no evidence of choledochal cyst or biliary dilation.

**Clinical Implications** This case demonstrates that gallbladder polyposis in MLD can cause life-threatening hemobilia, even as the presenting manifestation in a child without prior neurological diagnosis. Clinicians managing patients with MLD, especially those with progressive dysphagia, should be aware of this complication. The authors note that gallbladder polyps are found in 23% of MLD patients on ultrasound, and any gallbladder abnormality in 77%. Van Rappard et al recommended screening all MLD patients and performing laparoscopic cholecystectomy for polyps >5 mm or wall thickening to prevent malignancy and bleeding. However, the decision must balance risks with the patient's life-limiting disease. MLD should be considered in the differential diagnosis for children presenting with developmental regression and gastrointestinal bleeding.