P 520. Unclear Strokes in Pediatrics—Adenosine Deaminase 2 (ADA2) Deficiency as a Therapeutic Relevant Differential Diagnosis to Acquired Inflammatory CNS Diseases

Background: Adenosine deaminase 2 (ADA2) deficiency is an autosomal recessive disease and is caused by a mutation in the CECR1 gene. ADA2 deficiency goes clinically along with inflammatory changes mainly affecting small blood vessels leading to repeated cerebral ischemias, persistent temperature, muscle pain, skin changes (livedo reticularis), hepatosplenomegaly, and renal disorders. First symptoms are seen in the first decade of life.

Aims: Early diagnosis and initiation of adequate immunosuppressive therapy up to (pre-) symptomatic stem cell transplantation is crucial for the prognosis of the patients.

Question: When to consider ADA2 deficiency as a differential diagnosis in children with cerebral strokes?

Methods: We present two patients with genetic confirmed compound heterozygote mutations in the CECR1 gene. In patient 1, hypertonia was detected in a routine well-child visit at the age of 12 years. Performed renal biopsy revealed the diagnosis of a focal-segmental glomerulosclerosis. After some months, the patient presented with vertigo, acute gait disorder due to bilateral loss of sensibility, as well as internuclear ophthalmoplegia. Cerebral magnetic resonance imaging showed several old ischemias and one subacute.

Under prednisolone and subsequent additional immunosuppressive therapy, rapid improvement of symptoms was seen.

Patient 2 was first presented due to persistent vertigo at the age of 10 years. Under prednisolone therapy prescribed by an ENT specialist, the clinical symptoms improved rapidly. At the age of 11 years, the patient was presented due to muscle pain and persistent temperature over 3 weeks without focus. Further diagnostics revealed ubiquitous lymph node swelling, hepatosplenomegaly, livedo reticularis, focal nephritis with hypertonia, as well as cerebral ischemias with neurological defects. Under prednisolone treatment temperature, hypertonia, and inflammation parameters improved quickly. No further cerebral lesions were detected after initiation of immunosuppressive therapy with prednisolone and azathioprine.

Result: In both cases, acute clinical problems as well as long-term stabilization of the disease could be achieved by immunosuppressive therapy.

Conclusion: ADA2 deficiency is an autosomal recessive multisystemic disease causing cerebral strokes in early childhood as well as renal damage mainly due to a vasculitis. Long-term complications can be avoided by early immunosuppressive therapy; therefore, in case of clinical suspicion further molecular genetic testing and if necessary measurement of enzyme activity should be performed rapidly. Alternatively stem cell transplantation at an early stage should be discussed under consideration of risks and benefits.