Thrombotic Microangiopathy (TMA) after Gene Replacement Therapy (GRT) Due to Spinal Muscular Atrophy: Case Summary and Recommendations for Treatment

Background/Purpose: 5q-associated spinal muscular atrophy is one of the most severe and common genetic diseases. In the last few years, innovative methods of therapy have been developed based on SMN2 gene modification, such as splicing, or replacement of the damaged SMN1 gene (gene replacement therapy, GRT). GRT is known to be accompanied by off target effects like temporary elevation of liver and cardiac enzymes usually without serious clinical relevance.

Methods: A case report - We report a 4-year-old girl suffering from thrombotic microangiopathy (TMA) after GRT due to 5q- SMA.

Results/Case Summary: A 4-year-old girl developed TMA indicated by hemolytic anemia and thrombocytopenia in conjunction with renal failure 7 days after GRT with onasemnogene abeparvovec. The latter was characterized by a rise in serum creatinine, oliguria, hypertension, protein- and hematuria, and edema. The patient was started on eculizumab and antihypertensives resulting in normalization of hemolytic activity, platelet count, kidney function and blood pressure within one week.

Conclusion: SMA patients receiving GRT should undergo close monitoring for early detection of TMA. Adequate measures for TMA including eculizumab or plasmapheresis as well as renal replacement therapy should be available without delay in order to avoid progressive kidney disease or other severe complications in these patients. Careful follow-up including assessment of proteinuria and blood pressure is recommended since patients may require antihypertensive/nephroprotective treatment to avoid chronic kidney disease in later life. Therefore, GRT in SMA patients should only be performed at centers offering comprehensive multidisciplinary pediatric care.

Publication History

Article published online:
28 October 2021