Abstract
A 19-Year-Old Presenting with Severe Upper Gastrointestinal Bleeding: A Case Report fo the First Reported Joubert Syndrome with Hepatic Defect in the Philippines
Kathleen Singidas, MD
Vicente Sotto Memorial Medical Center
Background: Joubert Syndrome (JS) is a rare neurodevelopmental disorder with an estimated prevalence of 1 in 80,000 to 100,000 live births. It is characterized by cerebellar ataxia, hypotonia, developmental delay, and the hallmark “molar tooth sign” (MTS) on brain imaging. Even rarer is JS with hepatic defects (JS-H), which occurs in 6% to 14% of cases and is typically associated with congenital hepatic fibrosis (CHF). This report documents the first genetically confirmed case of JS-H in the Philippines, highlighting the importance of recognizing this condition in patients with unexplained liver disease and neurological symptoms. Early genetic testing and multidisciplinary care are crucial for improving patient outcome.
Clinical Presentation: A 19-year-old male from Cebu, with developmental delay, dysarthria, ataxia, jaundice, and abdominal distention, presented at the emergency department with massive hematemesis and melena. Family history revealed a younger sibling with similar neurological symptoms but no signs of liver involvement. Other family members were clinically well. Laboratory results showed severe anemia, pancytopenia, elevated liver enzymes, and coagulopathy, indicating liver dysfunction. Imaging confirmed liver cirrhosis, splenomegaly, and ascites. Esophagogastroduodenoscopy revealed type 1 gastroesophageal varix. A cranial CT scan demonstrated the hallmark MTS. Genetic testing identified pathogenic variants in the TMEM67 gene (NM_153704.6:c.2086C>T and NM_153704.6:c.431del), confirming JS-H. A comprehensive work-up excluded other potential causes of advanced liver fibrosis, such as viral, metabolic, autoimmune, hematologic, and structural conditions. The patient was managed with blood transfusions, octreotide, beta-blockers, prophylactic antibiotics, diuretics, and nutritional support. Due to equipment limitations in our setting, endoscopic management was not performed, and medical management was optimized. The patient was discharged in improved condition. Genetic counseling was provided and regular screening for hepatocellular carcinoma was advised.
Recommendation: Future research should explore the pathophysiology of TMEM67 mutations and the epidemiology of JS-H in the country to improve early diagnosis and intervention.
Important Dates to Remember
| JRRE Activities 2023-2024 |
Proposed Dates |
|---|---|
| Resumption of face-to-face Evidence-Based Medicine Workshop Venue to be announced once finalized. |
July 21, 2023 (Friday), 1-5pm |
| Monthly Critical Appraisal of Topics Conferences to be gaciliated by Research Coordinators per Institution | Monthly Critical Appraisal of Topics Conferences per Institution |
| CAT Plenary/Liver Con Dates: September 23, 2023 December 16, 2023 March 2024 (During the JAC) Resumption of face-to-face Quarterly Critical Appraisal of Topics facilitated by the JRRE |
2 Clinical scenarios and articles are to be sent to institutions each on August 2023, November 2023, and February 2024; |
| Hybrid Research Workshop 4 week asynchronous via Moodle, followed by a 1 day on-site Onsite Workshop Research Protocol Presentation for Level I GI Fellows-In-Training - Research Protocol Presentation: August 12, 2023 - Research Forums of the Tripartite Societies |
Week 1: July 15-21, 2023 Week 2: July 22-28, 2023 Week 3: July 29-August 4, 2023 Week 4: August 5-11, 2023 |
| Research Manuscript Workshop for level II GI Fellows-In-Training | January 6, 2024 |