1. Clinical Correlations The NYU Langone Online Journal of Medicine http://clinicalcorrelations.org

2. NYU Medicine Grand Rounds Clinical Vignette Anjali Varma Desai Medicine PGY-2 Resident January 15 th, 2014 U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS

3. 30 year old Caucasian woman presents with nausea, vomiting, abdominal pain for five days, and syncope on day of presentation Chief Complaint U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS

4. Nasal septum surgery in August 2010 Post-operative constipation, abdominal pain, nausea and vomiting Admitted to the hospital eight days post- operatively after syncopal episode History of Present Illness U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS

5. Hospital Course Symptoms self-resolved after five days Presumed diagnosis post-operative ileus U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS

6. Second Hospitalization Five weeks later, recurrent constipation, abdominal pain, nausea and vomiting Evaluated by Gastroenterologist and Gynecologist, no cause for symptoms found Hospitalized for seven days, discharged after symptoms self-resolved, no known diagnosis U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS

7. Third Hospitalization Five weeks later, hospitalized for recurrent symptoms Underwent endoscopy, colonoscopy, brain MRI, MRA, several subspecialties consulted Urine Aminolevulinic Acid (ALA) and Porphobilinogen (PBG) ordered U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS

8. Laboratory Testing 11/18/2010:  Urine PBG: 136.4 mg/24 hour (50x ULN) (normal 0- 2.7 mg/24 hour)  Urine ALA: 81.0 umol/L (2.3x ULN) (normal 0-35 umol/L) U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS

9. Diagnosis: Acute Hepatic Porphyria –Acute Intermittent Porphyria most common After 3 hemin infusions, discharged with symptom improvement Outpatient hemin infusions started Diagnosis and Next Steps U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS

10. Attacks recurred at 5 week intervals Timing of attacks closely related to menstruation Started Synarel on 2/10/11, no clear improvement in symptoms Outpatient Course U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS

11. Monthly prophylactic hemin infusions started, Synarel tapered off Notable labs:  Urine ALA 39.1 mg/L (5.6x ULN) (normal 0-7 mg/L)  Urine PBG 67.4 mg/L (16.9x ULN) (normal 0-4 mg/L)  Total porphyrins 3205 nmol/L (~10x ULN) (normal 0- 300 nmol/L) Medical Genetics Evaluation U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS

12. Hydroxymethylbilane Synthase (HMBS), Mutation L30P February 2012: started lupron, prophylactic schedule changed to biweekly Port placed December 2012; Estrogen therapy caused severe attack Medical Genetics Evaluation (continued) U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS

13. July 2013 started weekly hemin infusions Lupron discontinued, symptoms controlled Notable labs:  Urine ALA 11.8 mmol/m creat. (3.9x ULN) (normal 0.09-2.97 mmol/m creat.)  Urine PBG 47 mmol/m creat. (43.5x ULN) (normal 0- 1.08 mmol/m creat.) “High Excretion” Medical Genetics Evaluation (continued) U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS

14. No symptomatic family members Eastern European Ashkenazi Jewish on both sides No consanguinity 2 sisters (ages 30 and 40) Asymptomatic Heterozygotes Mother Asymptomatic Heterozygote Healthy 4 year old daughter Family History U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS

15. Family History U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS