D1.330 - Two different clinical presentations, two same immunological features in Purin nucleoside phosporilase deficiency

Introduction:Purin nucleoside phosporilase (PNP) deficiency manifests with immunodeficiency, autoimmune hemolytic anemia, and diverse neurological symptoms such as ataxia and developmental delay. We present two cases diagnosed with PNP deficiency who presented with different clinical presentations.

Case 1:Twenty two-month-old male patient was admitted with a urticarial rash that had persisted for three weeks. In his medical history, it was learnt that he had bronchiolitis two times and received treatment for urinary tract infection. By 16 months, her parents noticed that he could walk without support. He is the second child of his consanguineous parents. He could sit without support but could not walk without support. The patient had lymphopenia (absolute lymphocyte count (ALC):680 cells/mm3). Serum immunoglobulin levels were normal. He displayed moderately reduced CD4+ and CD8+ T cell numbers. CD45RA+ naive T cells constituted 17.2% of CD4+ T cells. Serum uric acid level was at the lower limit of the normal (0,1mg/dl).Whole Exome Sequencing (WES) analysis is showed a homozygous missense variant (NM_000270.4 c.59_60delinsCT p.(His20Pro))  in the PNP gene.

Case 2:Twenty one month-old girl was consulted to the our clinic for PNP deficiency was detected in genetic analysis. In her history, it was learned that she was hospitalized two times for urinary tract infection and once for bronchopneumonia. By 12 months, her parents noticed that she could not sit or walk without support. She is the first child of nonconsanguineous parents. She could sit without support but could not walk without support. The patient exhibited lymphopenia (ALC:590 cells/mm3). Serum immunoglobulin levels were normal. She displayed moderately reduced CD4+ and CD8+ T cell numbers. CD45RA+ naive T cells constituted 1.1% of CD3+ T cells. Serum uric acid level was at the lower limit of the normal (0,0mg/dl). Erythrocyte PNP activity measured 93.9 nmol/h/mg (normal level: 1,354±561 nmol/h/mg). Whole exome sequencing analysis showed a homozygous missense variant (c.2T>G) in the PNP gene.

Conclusion:The diagnosis of PNP deficiency may be delayed if infectious findings appear later than neurological symptoms, making accompanying lymphopenia a crucial warning sign. Clinicians should be alert for immune deficiency in cases involving neuromotor developmental delay and lymphopenia.