[Thrombotic Microangiopathy (TMA) after Gene Replacemant Therapy (GRT) due to Spinal Muscular Atrophy: Case Summary and Recommendations for Treatment].

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

CASE SUMMARY: A 4-year-old girl developed TMA indicated by haemolytic 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 haematuria, and oedema. The patient was started on eculizumab and antihypertensives resulting in normalization of haemolytic activity, platelet count, kidney function and blood pressure within one week.

RECOMMENDATION AND 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 with neuropediatric and paediatric nephrology expertise.