Gene Mutation

Rei is a 53-year-old female, who decides to visit her GP as she has been feeling tired a lot. She often feels thirsty and has noticed she needs to urinate more frequently. The GP comments on Rei’s skinny appearance and asks if she had any weight changes recently. Rei realises she has been buying smaller sized clothes recently even though she had not experienced rapid changes in weight previously. The doctor examines Rei and notes she has a sweet, fruity odour to her breath. The doctor also orders both urine and blood tests for Rei, which gave the following results:

Assessment/Examination Results
Urine dipstick test — glucose +++
Urine dipstick test — ketones ++
Plasma glucose (fasting) 18 mmol/L
Bicarbonate 12.5 mEq/L
Arterial PaCO2 29 mmHg
Blood pH 7.25
Plasma insulin < 5 mU/L
HbA1c 9%

After diagnosing her condition, the GP helps Rei to develop a management plan.

Question 2/1 Name the underlying disease Rei is suffering from and justify your answer using two pieces of information from the clinical picture to support your conclusion.
(1.5 marks)

Question 2/2 Evaluate Rei’s laboratory findings, name the acute complication Rei was suffering from when she visited her GP, and explain your reasoning. (1.5 marks)

Question 2/3 Discuss the pathophysiology behind the complication you identified under Question 2/2. Make sure that you state relevant evidence from her laboratory results and/or history. (4 marks)

Question 2/4 Possible long-term complications of Rei’s present condition are nephropathy and consequent renal failure. Discuss the link between Rei’s underlying disease and nephropathy. (3 marks)

Question 2/5 Discuss the significance of Rei’s HbA1c reading. (2 marks)

Rei’s aunt has been suffering from diabetes mellitus and has been using insulin to manage her condition for 20 years.

Question 2/6 Explain the reasons diabetic patients (may) require exogenous insulin administration and discuss the need for using short- and long-acting preparations. In your answer, explain why administration of insulin tablets would be useless. (3 marks)

Rei’s aunt has been feeling tired all the time recently despite the successful management of her diabetes. She has also noticed that she has stiff and sore wrists. Intriguingly, the stiffness she experiences in her fingers as well is particularly severe when she goes to have her morning cigarette. She also finds that her fine finger movements have become much harder when rolling her cigarettes. Her GP completes a physical exam and notes that her joints are swollen and warm to the touch.

Question 2/7 Name the musculoskeletal disorder Rei most likely suffers from, justify your answer, and identify a risk factor in her history that may have contributed to the aetiology of the disease you specified. (2 marks)

Question 2/8 Compare and contrast the aetiology of Rei’s joint disease with the other joint disease we covered in In your answer, name both diseases and describe two similarities and two differences between them. (3 marks)

Rei’s work colleague, Kurt, is a 53-year-old father, who has worked as a gardener all his life. He has been diagnosed with stage IVA melanoma. Kurt underwent removal of the melanoma on his left forearm and a nearby lymph node dissection 7 weeks ago. He has been receiving immunotherapy for his melanoma, bit it has not been successful and therefore he has now been placed on chemotherapy. Kurt has been experiencing weight loss over the last 2 months as well as a persistent cough and shortness of breath. A CT scan reveals several, well circumscribed, rounded structures in the periphery of his lungs. A lung biopsy is performed, which confirms the presence of melanoma cells in the structures observed on the CT image.

Question 2/9 Discuss the significance of Kurt’s CT and histology findings. (2 marks)

Question 2/10 Further laboratory testing has indicated a p53 gene mutation in Kurt’s melanoma cells. Explain the possible link between Kurt’s p53 mutation and his melanoma, and considering Kurt’s profession, name a possible environmental factor that may have caused his mutation. (3 marks)