2835Complications and management of pregnancy in Danon disease

Abstract

Introduction/Description of problem: Danon disease is a rare X-linked dominant lysosomal glycogen storage disease caused by mutations in the Lysosomal- Associated Membrane Protein 2 or (LAMP2) gene. Compared to males, affected females present later and with milder phenotypes. Specifically, females usually manifest with hypertrophic cardiomyopathy (HCM) and electrical abnormalities, whereas skeletal myopathy and intellectual disability, may either be absent or exhibit milder phenotype in women. Despite later onset of HCM in females with Danon disease, the severity of life-threatening arrhythmias may complicate the evolution of HCM in female patients, and nearly one-fifth undergo cardiac transplant. Cardiac complications and associated management during pregnancy however have not been well-elucidated in these patients. Case: We describe a young female with Danon disease who had three pregnancies and three prenatal diagnoses. She was the daughter of a 44-year old female evaluated in our centre for HCM, which rapidly evolved through left ventricular (LV) dilation and end-stage heart failure, and resulted in death while awaiting heart transplant. Our patient underwent genetic counseling addressing maternal risk, risk of transmission, and the different severity of phenotype in males and females. The first prenatal test showed a male fetus without the maternal mutation in LAMP2 (successful spontaneous delivery). The second showed a positive prenatal test in a male fetus (pregnancy terminated). During these two pregnancies, the patient did not develop arrhythmias. The third prenatal diagnosis showed a female carrier of the maternal genetic defect. In addition, she had recurrent supraventricular and ventricular arrhythmias during the latter pregnancy, leading to uptitration of beta-blocker therapy and caesarean section at 35 weeks 5 days. After delivery, the arrhythmias dramatically improved. Cardiac magnetic resonance imaging after the third pregnancy versus prior to pregnancies showed progression of LV wall thickening and presence of myocardial fibrosis. Three years after delivery, the patient developed paroxysmal atrial fibrillation, successfully controlled by sotalol. At this time, she remains stable in sinus rhythm. Discussion/Conclusions: This case underscores important messages. Firstly, it supports that females with Danon disease should be informed of different phenotype severity in male versus female patients/offspring. Secondly, although it is known that pregnancy can alter the arrhythmogenic profile overall, management of cardiac phenotype worsening triggered by pregnancy in Danon disease has not been discussed in the literature. This case importantly highlights that it is indeed a possibility. Considering the maternal effort during the expulsion stage in standard vaginal delivery, we suggest planning a caesarean section around 36-38 weeks of pregnancy. At this phase, the fetus is safe and the mother is exposed to minor cardiovascular stress.