Foundation for Biomedical Research, La Paz University Hospital (FIBHULP), IdiPaz, Madrid, Spain; Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Spain.
Department of Pediatrics, University Hospital Rio Hortega, Valladolid, Spain.
Clin Chim Acta. 2017 Sep;472:136-138. doi: 10.1016/j.cca.2017.08.002. Epub 2017 Aug 3.
Complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity causes Lesch Nyhan disease (LND), characterized by hyperuricemia, severe action dystonia, choreoathetosis, ballismus, cognitive and attention deficit and self-injurious behavior. Partial HPRT deficiency is present in patients with Lesch-Nyhan variant (LNV), who present with HPRT-related gout and a variable degree of neurological involvement. The diagnosis of HPRT deficiency relies on clinical, biochemical, enzymatic and molecular data. Patients with HPRT deficiency present low or undetectable HPRT activity in hemolysates, with increased adenine phosphoribosyltransferase (APRT) activity. We present a 9-year-old boy who experienced an episode of macroscopic hematuria with dysuria and left flank pain. He presented hyperuricemia and hyperuricosuria. HPRT and APRT activities were both normal in hemolysate; however, HPRT activity assayed in intact erythrocytes was 50% of control levels. A new missense point mutation c.424 A>G (T142A) was found in the HPRT1 gene. The apparent Michaelis constant (Km) for 5-phosphoribosyl-pyrophosphate assayed in patient hemolysate was 20-fold of control levels. In conclusion, we report a patient with HPRT deficiency who presented with both normal HPRT and APRT activity in hemolysate, in which the enzyme activity determined in intact erythrocytes was of diagnostic utility.
次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HPRT）完全缺乏可导致 Lesch-Nyhan 病（LND），其特征为高尿酸血症、严重动作性肌张力障碍、舞蹈手足徐动症、投掷症、认知和注意力缺陷以及自残行为。Lesch-Nyhan 变异型（LNV）患者存在部分 HPRT 缺乏，其表现为与 HPRT 相关的痛风和不同程度的神经受累。HPRT 缺乏的诊断依赖于临床、生化、酶学和分子数据。HPRT 缺乏症患者的溶血物中 HPRT 活性低或检测不到，腺嘌呤磷酸核糖转移酶（APRT）活性增加。我们介绍了一名 9 岁男孩，他经历了一次肉眼血尿伴尿痛和左侧腰痛发作。他表现为高尿酸血症和高尿酸尿症。溶血物中 HPRT 和 APRT 活性均正常；然而，完整红细胞中 HPRT 活性为对照水平的 50%。在 HPRT1 基因中发现了一个新的错义点突变 c.424 A>G（T142A）。患者溶血物中 5-磷酸核糖基-焦磷酸的表观米氏常数（Km）是对照水平的 20 倍。总之，我们报告了一名 HPRT 缺乏症患者，其溶血物中 HPRT 和 APRT 活性均正常，而完整红细胞中的酶活性具有诊断意义。
