Introduction: Complete or near complete absence of the purine nucleoside phosphorylase (PNP) enzyme causes a profound T cell immunodeficiency and neurological abnormalities that are often lethal in infancy and early childhood. We hypothesized that patients with partial PNP deficiency, characterized by a late and mild phenotype due to residual PNP enzyme, would provide important information about the minimal PNP activity needed for normal development.

Methods: Three siblings with a homozygous PNP gene mutation (c.769C>G, p.His257Asp) resulting in partial PNP deficiency were investigated. PNP activity was semi-quantitively assayed by the conversion of [14C]inosine in hemolysates, mononuclear cells, and lymphoblastoid B cells. PNP protein expression was determined by Western Blotting in lymphoblastoid B cells. DNA repair was quantified by measuring viability of lymphoblastoid B cells following ionizing irradiation.

Results: A 21-year-old female was referred for recurrent sino-pulmonary infections while her older male siblings, aged 25- and 28- years, did not suffer from significant infections. Two of the siblings had moderately reduced numbers of T, B, and NK cells, while the other had near normal lymphocyte subset numbers. T cell proliferations were normal in the two siblings tested. Hypogammaglobulinemia was noted in two siblings, including one that required immunoglobulin replacement. All siblings had typical (normal) neurological development. PNP activity in various cells from two patients were 8–11% of the normal level. All siblings had normal blood uric acid and increased PNP substrates in the urine. PNP protein expression in cells from the two patients examined was similar to that observed in cells from healthy controls. The survival of lymphoblastoid B cells from 2 partial PNP-deficient patients after irradiation was similar to that of PNP-proficient cells and markedly higher than the survival of cells from a patient with absent PNP activity or a patient with ataxia telangiectasia.

Conclusions: Patients with partial PNP deficiency can present in the third decade of life with mild-moderate immune abnormalities and typical development. Near-normal immunity might be achieved with relatively low PNP activity.

介绍：嘌呤核苷磷酸化酶（PNP）酶的完全或接近完全缺乏会导致严重的T细胞免疫缺陷和神经系统异常，这些异常通常在婴儿期和儿童早期就具有致命性。我们假设具有部分PNP缺乏症的患者，其特征是由于残留的PNP酶而出现了晚期和轻度的表型，将提供有关正常发育所需的最低PNP活性的重要信息。

方法： 三个纯合的兄弟姐妹 PNP研究了导致部分PNP缺乏的基因突变（c.769C> G，p.His257Asp）。通过在溶血产物，单核细胞和淋巴母细胞B细胞中[14C]肌苷的转化，半定量测定PNP活性。通过蛋白质印迹法在淋巴母细胞B细胞中确定PNP蛋白表达。通过测量电离辐射后淋巴母细胞B细胞的活力来定量DNA修复。

结果：一名21岁的女性因复发性肺部肺炎而被转诊，而其年龄较大的25岁和28岁的男性同胞并未受到重大感染。其中两个同胞的T，B和NK细胞数量有所减少，而另一个则具有接近正常的淋巴细胞亚群数量。在测试的两个兄弟姐妹中，T细胞增殖是正常的。低血球蛋白血症发生在两个兄弟姐妹中，其中一个需要更换免疫球蛋白。所有兄弟姐妹都有典型的（正常）神经系统发育。来自两名患者的各种细胞中的PNP活性为正常水平的8-11％。所有兄弟姐妹的尿酸水平正常，尿液中PNP底物增加。两名患者的细胞中PNP蛋白表达与健康对照组细胞中的PNP蛋白表达相似。

结论：部分PNP缺乏症患者可在生命的第三十年出现轻度-中度免疫异常和典型发育。较低的PNP活性可以达到接近正常的免疫力。