A novel PNP variant causes lymphopenia, hypouricemia and neurological deficit

Authors

  • Intan Juliana Abd Hamid Primary Immunodeficiency Diseases Group, Department of Clinical Medicine, Institut Perubatan & Pergigian Termaju, Universiti Sains Malaysia, Bertam, Malaysia
  • Bee Chin Chen Biochemical Genetic Laboratory & Clinical Genetics, Department of Genetics, Kuala Lumpur Hospital, Malaysia
  • Huey Yin Leong Biochemical Genetic Laboratory & Clinical Genetics, Department of Genetics, Kuala Lumpur Hospital, Malaysia
  • Yusnita Yakob Molecular Diagnostics and Protein Unit, Institute for Medical Research, Kuala Lumpur, Malaysia
  • Nor Azimah Abd Azize Molecular Diagnostics and Protein Unit, Institute for Medical Research, Kuala Lumpur, Malaysia
  • Mohd Khairul Nizam Mohd Khalid Inborn Errors of Metabolic and Genetic Unit, Institute for Medical Research, National Institute of Health, Malaysia
  • Gaik Siew Ch'ng Biochemical Genetic Laboratory & Clinical Genetics, Department of Genetics, Kuala Lumpur Hospital, Malaysia
  • Wee Teik Keng Biochemical Genetic Laboratory & Clinical Genetics, Department of Genetics, Kuala Lumpur Hospital, Malaysia
  • Lock Hock Ngu Biochemical Genetic Laboratory & Clinical Genetics, Department of Genetics, Kuala Lumpur Hospital, Malaysia

Keywords:

Purine nucleoside phosphorylase, Severe combined immunodeficiency (SCID), Inborn Errors of Immunity

Abstract

Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive disorder of the purine metabolism and salvage pathway caused by mutations in the PNP gene. This disorder leads to progressive severe combined immunodeficiency (SCID) and neurological impairment. We report on identification of a 5-year-old Malaysian-Thai girl who presented with T–B–NK–SCID phenotypes and a novel PNP gene mutation. A full analysis of the clinical phenotypes, immunological investigations, and molecular study was performed.

She initially presented with spastic diplegia and isolated motor developmental delay. Her blood tests showed lymphopenia and profound hypouricemia, which prompted further investigations for purine deficiency.  Urine purine nucleosides, including inosine, guanosine and deoxylated forms, were grossly elevated. The diagnosis was further confirmed by detection of low PNP enzyme activity in hemolysate.  Analysis of the PNP gene revealed a novel homozygous mutation c.550C>T, p.(Gln184Ter). Our report highlights the importance of evaluating for SCID in patients presenting with lymphopenia, hypouricemia, and neurological manifestations.

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Published

2025-03-05

How to Cite

1.
Abd Hamid IJ, Chen BC, Leong HY, Yakob Y, Abd Azize NA, Mohd Khalid MKN, Ch’ng GS, Keng WT, Ngu LH. A novel PNP variant causes lymphopenia, hypouricemia and neurological deficit. PI [Internet]. 2025Mar.5 [cited 2025Apr.28];65(2). Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/3545

Issue

Vol. 65 No. 2 (2025): March 2025

Section

Case Report

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Copyright (c) 2025 Intan Juliana Abd Hamid, Bee Chin Chen, Huey Yin Leong, Yusnita Yakob, Nor Azimah Abd Azize, Mohd Khairul Nizam Mohd Khalid, Gaik Siew Ch'ng, Wee Teik Keng, Lock Hock Ngu

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Received 2023-08-04
Accepted 2025-03-04
Published 2025-03-05