INTRODUCTION

We’re fascinated with the concept of open collaboration for biomedicine research. The expandability of bright minds working on difficult medical problems is what drives our research events. Undiagnosed #1 is our first patient collaboration focusing on an unknown genetic condition. In Spring 2019 we will bring together a group of Engineers and Researchers to look for answers and create medical insights into this patients unresolved condition.

SVAI has produced two patient oriented research hackathons to date, held in Spring 2017 and Spring 2018. Both research hackathons were hosted in San Francisco California and brought together hundreds of researchers and engineers to advance medical insights for rare disease. Both events created a range of analysis including cancer clustering algorithms, gene expression, and drug target pathways. Learn more: Neurofibromatosis Type 2 (NF2), Papillary Renal-Cell Carcinoma Type 1 (p1RCC)

PURPOSE

  • Contribute to a real, ongoing patient case.

  • Advance research and medical insights for rare and undiagnosed diseases.

  • Create interdisciplinary research opportunities for computer scientists and biologists.

  • Education and skills development in AI/ML, computational biology, genomics and data science.

  • Build a thriving community for open, collaborative biomedicine.

CASE BACKGROUND

As a baby, Mr. Mickel reports a history of vomiting after breastfeeding and FTT. Since childhood, he has had significant issues gaining weight despite adequate caloric intake, though his height has always remained on the curve. As a child, he reports a history of nausea, stomach aches and an overall aversion to food. He remembers having minimal muscle mass and being easily fatigued.

His GI issues became more severe in his 20’s when he began to have daily lower abdominal pain characterized by burning and nausea. He also began to have abdominal distension with minimal food intake. He was diagnosed with visceral hypersensitvitiy. During his 20’s he also developed chronic vomiting daily and vomited as many as 5 times per day. He had extensive workup including multiple EGDs, small bowel xray series, CT enterography, capsule endoscopy, nuclear gastric emptying studies and antral duodenal motility study. Findings have been notable for delayed gastric emptying, question of gastroparesis based on antral duodenal motility study, duodenal ulcer, and mild increase in IELs on full thickness jejunal biopsy. He saw an ENT to address his vomiting was told that his uvula was causing the episodes and had it removed. Mr. Mickel reports that since then he no longer experiences vomiting, though it has not resolved his other GI issues.

Currently his height is 5’10” and weight is 109lbs. The heaviest he has been is ~124lbs, which he reports was when he was frequently using cannabis and taking benzodiazepines. Due to his low weight he has very limited muscle mass and is easily fatigued. He reports pain and weakness in his knees and has had a couple disc herniations as well as shoulder dislocations. He has attempted to build muscle mass on occasion with lifting and protein, but this has not been successful due to GI issues and pain.

Mr. Mickel has tried many medications including PPIs, H2 blocker, low dose E-Mycin, Baclofen, Cymbalta, Nortriptyline, Amitriptyline, Mirtazepine, Zofran, Remeron, Etopiride, Cinetopride, Lyrica, Gabapentin, Benzodiazepines, prednisone and IVIG. He reports that the benzodiazepines helped the most with his abdominal pain and burning, however, he did not like the other side effects and has not taken this medication for several years. He also tried adipose stem cells and had significant improvement in his muscle tone and mobility, but this wore off in a year. He also reports undergoing two fecal transplants that he administered to himself and were not overseen by a physician and he did not get any symptom relief.

He has also had extensive biochemical evaluations and genetic testing. Biochemical evaluations in the past were revealing for increased urinary lactate. Serum markers have been inconsistent, with high ethylmalonic acid and mild metabolic alkalosis. Whole exome sequencing was revealing for multiple variants of uncertain significance as summarized below. Based on the variants in his ALDOB gene he was told that he might have HFI and abided by a strict diet for over a month with no improvement in symptoms.

Review of systems is otherwise notable for frequent urination and constant pelvic discomfort. Mr. Mickel does not report pain when urinating, and instead reports burning pain in his abdomen. He has never had a full urology evaluation. He reports a history of frequent fungal infections on his chest and multiple plantar warts. He had a normal cardiology workup including normal echo and stress test.