User:Group4shumpert/sandbox

Wiki Assignment 1 (Melanie)

Contributors: Lee Lee Kelly, Alex Schaffer, Badr Abdullah, Joe Pryor, Salonee R, Dilpreet Singh Background

Melanie has fallen while roller-skating (she's a cool kid) and although the fall was minor, she's broken her leg. She is always tired, has an extremely bloated abdomen, with an enlarged spleen and liver. She’s of Eastern European Jewish ancestry, has low blood platelet counts, and has an increased susceptibility to infections. What disease does she have? What's the root cause of this disease? What are the two most “popular” treatments? Can you imagine another more “permanent” cure? (AS)

Diagnosis

Melanie's presentation is consistent with Gaucher's disease, where organomegaly of the spleen and liver create a bloated appearance of the abdomen and osteopenia that leads to an increased susceptibility to fractures. This may also lead to hematological abnormalities such as a factor XI deficiency, leading to Hemophilia C which is coincidentally common in people of Ashkenazi descent (BA).

Beta-Glucosidase leukocyte blood test is a standard tool to test the glucocerebrosidase level (SR). Yet, this test cannot determine one's carrier status for this disease. One can be a carrier for the disease and pass it down to their children without actually developing the disease themself (DS).

Causes

Gaucher disease is caused by a deficiency in glucocerebrosidase, which leads to increased lipid deposition in the bone marrow, spleen, and liver (BA). The enzyme glucocerebrosidase breaks down glucocerebroside (a fatty chemical), and Gaucher cells are macrophages that get accumulated with glucocerebroside because of the low levels of glucocerebrosidase (DS). This consequently causes numerous hematological and skeletal issues such as anemia, and osteopenia, alongside organomegaly of the spleen and liver (BA).

The glucocerebrosidase deficiency in Gaucher disease is caused by a mutation in the GBA gene. Gaucher disease is autosomal recessive, meaning that an individual must inherit two mutated copies of the GBA gene in order for the condition to manifest. It is estimated that 1 in 14 individuals of Ashkenazi Jewish descent carry a copy of the mutation. (JP)

Treatment

Melanie's treatment options include:

1. Enzyme replacement therapy (ERT) with recombinant enzyme imiglucerase. Effective in reversing hematologic symptoms such as organomegaly, anemia and thrombocytopenia (BA). It is delivered using IVs every two weeks (SR).

2. Substrate reduction therapy (SRT) via Glucosylceramide synthase inhibitors to reduce the amount of glucocerebroside buildup in patients. This method may be used when ERT is not possible (BA).

3. The more permanent option would be to reverse the mutation that leads to the deletion of the gene responsible for coding glucocerebrosidase, thereby preventing the metabolic abnormalities that lead to Gaucher disease (BA). Using technology such as CRISPR would be a great tool (SR). However, the implications of genetic alterations are still not fully understood, and 100% accuracy has still not been achieved; therefore, it would be a decision the parents, medical providers, and insurance company would each need to agree upon (LLK).

A preventative method would be Genetic counseling or Amniotic fluid testing (SR). Given that this is an autosomal recessive disorder, if Melanie decides years later to have children, she could have her partner tested for the faulty GBA gene. If he isn't a carrier or affected, none of their children would be at risk (LLK).

(Proofread and edited by Lee Lee Kelly)