Clinical Correlations The NYU Langone Online Journal of Medicine

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

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

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

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

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

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

Laboratory Testing 11/18/2010:  Urine PBG: mg/24 hour (50x ULN) (normal 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

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

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

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 nmol/L) Medical Genetics Evaluation U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS

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

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

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

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