Purine Nucleoside Phosphorylase Deficiency in a Patient With Spastic Paraplegia and Recurrent Infections

Abstract

Purine nucleoside phosphorylase deficiency is a rare autosomal recessive immunodeficiency disease. The characteristic features of the disease include severe T cell immune defects with recurrent infections, a failure to thrive, and progressive neurological findings. To date, 35 cases of purine nucleosidase phosphorylase deficiency have been reported worldwide. A 2-year-old female patient was hospitalized due to recurrent infections starting from 6 months and a fever that had continued for a month. The parents were first cousins. Physical examination showed a failure to thrive, herpetic lesions around the lips, painful lesions on the tongue and the buccal mucosa, lung infection, and spastic paraparesis in the lower extremities. She had motor and mental retardation. Laboratory tests revealed lymphopenia; low CD3, CD4, and CD8 counts; normal immunoglobulin levels; low uric acid; and very low purine nucleoside phosphorylase enzyme activity (1.4 nmol/h/mg; normal range, 490-1530). DNA sequencing of the purine nucleosidase phosphorylase gene revealed a missense homozygous mutation, a G to A transition at exon 4 position 64 (349G>A transition), which led to a substitution of alanine by threonine at codon 117 (Ala117Thr). Both parents were heterozygous for the mutation. This is the second purine nucleosidase phosphorylase deficient case to have been presented and carrying this mutation worldwide. Various antibiotics, antifungal drugs, and intravenous immunoglobulin were used to treat the infections during her 3 months. This form of treatment proved to be unresponsive, resulting in her subsequent death at 26 months of age.

A successful unrelated peripheral blood stem cell transplantation with reduced intensity‐conditioning regimen in a patient with late‐onset purine nucleoside phosphorylase deficiency

“…Genetic analysis revealed homozygous missense mutation (p. A117T), which causes a c.349G>A amino acid substitution in PNP gene in exon 4, which has previously been reported . Additionally, a homozygous G/A polymorphic site in IVS3 has also been detected, c.285 + 10G (IVS3 + 10G).…”

Novel Genetic Mutations in the First Swedish Patient with Purine Nucleoside Phosphorylase Deficiency and Clinical Outcome After Hematopoietic Stem Cell Transplantation with HLA-Matched Unrelated Donor

“…There were also a reduced number of Purkinje cells in the cerebellum, and the existing Purkinje cells had an abnormal shape. The two patients in our review who had undergone MRI had normal results, but some reported cases had abnormal MRIs (Ozkinay et al 2007;Madkaikar et al 2011;Somech et al 2013). One patient with substantial neurological impairment had an MRI late in the progress of the illness, showing atrophy of the cerebellum and the cerebral cortex with loss of white matter myelination (Ozkinay et al 2007).…”

“…The two patients in our review who had undergone MRI had normal results, but some reported cases had abnormal MRIs (Ozkinay et al 2007;Madkaikar et al 2011;Somech et al 2013). One patient with substantial neurological impairment had an MRI late in the progress of the illness, showing atrophy of the cerebellum and the cerebral cortex with loss of white matter myelination (Ozkinay et al 2007). Two other cases had mild to significant brain atrophy (Madkaikar et al 2011;Somech et al 2013).…”

Infectious and non-infectious complications in primary immunodeficiency disorders: an autopsy study from North India

“…The IL2RG gene was sequenced in 2/6 patients, in our series: however, no mutation was detected in the  IL2RG gene in these patients. SCID with PNP deficiency is rare and constitutes 4% of all SCID cases 13. Besides progressive combined immunodeficiency, it is characterised by progressive neurological symptoms including ataxia, developmental delay, tremors and spasticity.…”