(TCP007) HYPERGLYCEMIA WITH KETOSIS AS AN INITIAL PRESENTATION OF HEMOCHROMATOSIS

Abstract:

Background: Hereditary Hemochromatosis is an autosomal recessive disorder, characterized by iron overload and deposition in different body organs. It is one of the most common genetic disorders in people with European ancestry. A case of newly diagnosed Diabetes Mellites as an initial clinical clue towards diagnosing Hemochromatosis is presented.

Case: A 23-year-old woman, known for asthma and secondary amenorrhea, presented to the emergency department with a one-week history of polyuria, polydipsia, nocturia, and weight loss. Her family history is not significant for any genetic or systemic diseases. Physical examination was unremarkable, negative for skin discoloration, and revealed no signs of diabetes microvascular complications or chronic liver disease.
Investigations and clinical course: Complete blood count cells showed a hemoglobin level of 166 g/L.Random plasma glucose of 22 mmol/L. Venous Blood Gas: PH of 7.32. Bicarbonate: 25 mmol/L, AG: 14 mmol/L.Beta-hydroxybutyrate: 2.8 mmol/L. LH: 1.1 IU/L, FSH: 1.8IU/L, TSH: 4.64 mIU/L fT4: 10.61 pmol/L, Estradiol: < 55.1pmol/L, Progesterone: 1.17 nmol/L, AM cortisol: 270 nmol/L, Bioavailable Testosterone: 0.14 nmol/L.
The patient was started on subcutaneous insulin injections until further decisive investigation results were available to direct towards the diabetes etiology. The insulin requirements and her glycemic control suggest insulin deficiency early in the treatment course.
Anti-GAD antibodies: 1.9U/mL. C-peptide: 0.139 nmol/L. Ferritin > 4186 ug/L. Genetic test for hereditary hemochromatosis: single H63D mutation. Liver fibrous scan and MRI suggestive of severe hepatic iron overload. Liver biopsy: markedly increased stainable iron in hepatocytes. Cardiac MRI: Evidence of myocardial iron overload.
She was started on weekly phlebotomy and iron chelation therapy while awaiting further genetic workup.

Discussion: Hereditary Hemochromatosis is a relatively rare, multisystem disease, known for its association with Diabetes Mellites. The pathophysiology can be multifactorial, a mixture of insulin secretory defects and peripheral resistance. However, hyperglycemic emergencies with metabolic decompensations are uncommon first clinical encounters for this disease. The present case highlights two aspects that support the low penetrance nature of this disorder. The first aspect is the initial presentation of a hyperglycemic emergency in the form of ketosis. The second is the severe multisystem involvement at an early age, which generally presents after age 40.

Conclusion: The hemochromatosis case is an example of a multisystem disorder with extensive iron accumulation and deposition. Considering the low penetrance nature of the disease, it is essential to broaden the differential diagnosis in a newly diagnosed diabetes, especially when the presentation is not in the proper context.