HPRT1 Disorders

Clinical characteristics 临床特征:

HPRT1 disorders, caused by deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt), are typically associated with clinical evidence for overproduction of uric acid (hyperuricemia, nephrolithiasis, and/or gouty arthritis) and varying degrees of neurologic and/or behavioral problems. Historically, three phenotypes were identified in the spectrum of HPRT1 disorders: Lesch-Nyhan disease (LND) at the most severe end with motor dysfunction resembling severe cerebral palsy, intellectual disability, and self-injurious behavior; HPRT1-related neurologic dysfunction (HND) in the intermediate range with similar but fewer severe neurologic findings than LND and no self-injurious behavior; and HPRT1-related hyperuricemia (HRH) at the mild end without overt neurologic deficits. It is now recognized that these neurobehavioral phenotypes cluster along a continuum from severe to mild. 


HPRT1疾病是由次黄嘌呤-鸟嘌呤磷酸核糖基转移酶(HGprt)缺乏引起的,通常与过度生产尿酸 (高尿酸血症, 肾结石和/或痛风性关节炎) 以及不同程度的神经系统和/或行为问题的临床症状相关的一种疾病。从病历史上来看,HPRT1疾病谱中证实了有三种表型:最严重的是Lesch-Nyhan病 (LND) 型,其运动功能障碍类似于严重的脑瘫,且有智力残疾和自残行为; 中等型的是HPRT1相关的神经功能障 (HND) 型, 它与LND相似但没有其严重的神经系统症状,且没有自残行为; 还有一种是是轻微型的, 它是HPRT1相关性的高尿酸血症 (HRH) 型, 它通常没有明显的神经功能障碍。目前已经认识到,这些神经行为表型通常是从重度到轻度的连续聚集而一体的。

Diagnosis/testing 诊断/测试:

The diagnosis of an HPRT1 disorder is established in a male proband with suggestive clinical and laboratory findings and a hemizygous pathogenic variant in HPRT1 identified by molecular genetic testing and/or low HGprt enzyme activity identified on biochemical testing.

HPRT1疾病的诊断是基于男性患者有临床和实验室检查指标异常, 且 通过分子遗传学测试鉴定出有半合子HPRT1基因变异, 同时或者有生化测试发现HGprt酶活性降低。

Management 管理:

Treatment of manifestations:

Hyperuricemia is most commonly treated with the xanthine oxidase inhibitor allopurinol to reduce the risk for nephropathy, gouty arthritis, and tophi. Febuxostat may be used in case of allopurinol hypersensitivity. Multidisciplinary specialists may be needed to manage the neurologic manifestations. Depending on needs, specialists in medical genetics, neurology, behavioral management, developmental pediatrics, physical medicine and rehabilitation, physical therapy, occupational therapy, speech and language pathology, dentistry, and nephrology may be required.


高尿酸血症最常见是用黄嘌呤氧化酶抑制剂别嘌呤醇治疗,以降低发生肾病,痛风性关节炎和痛风石的风险。 如果别嘌呤醇过敏,可以使用非布索坦。 可能需要多学科专家来管理神经系统表现。 神经系统出现的症状可能需要多学科专家来管理治疗。 根据需要,可能需要医学遗传学,神经学,行为管理,儿科发育,物理医学和康复,物理治疗,职业治疗,言语和语言病理学,牙科和肾脏病学方面的专家共同参与.


HPRT1 disorders are not clinically progressive; however, surveillance is important for all HPRT1 disorders. While overproduction of uric acid does not get worse with time, chronic overproduction of uric acid – especially if not well controlled – may lead to cumulative pathology in the kidneys and/or joints. Similarly, new or worsening neurologic problems are not expected over time; however, some evolution of the neurologic problems occurs in the first few years of life, which reflects development of the nervous system in response to a static insult.


HPRT1疾病在临床上不是进行性的;但是,动态根踪观察对于所有HPRT1疾病型都很重要。 虽然尿酸的过量生产不会随着时间的推移而恶化,但慢性尿酸的长期的过量生产, 尤其是如果控制不佳, 可能会导致肾脏和/或关节的病理发展的累集。 同样,神经系统也是这样, 虽然其问题不会随着时间的流逝,出现新的或恶化的现象, 但在孩子的最初几年里神经问题的一些演变会影想到神经系统对静态电冲击发应的发育。

Agents/circumstances to avoid:

Probenecid and other drugs that increase the risk for precipitation of uric acid in the urinary system and may cause acute renal failure; certain chemotherapy agents, such as methotrexate, that block synthesis or use of purines; periods of relative dehydration because they increase the risk for renal stones or urate nephropathy.

避免药物/情况 :

丙磺舒和其他药物会增加尿酸在泌尿系统中沉淀的风险, 从而导致急性肾功能衰竭; 某些象甲氨蝶呤的化疗制剂 , 会阻止嘌呤的合成或使用; 相对脱水的时候会增加患肾结石或尿酸肾病的风险。

Evaluation of relatives at risk:

It is appropriate to clarify the status of males at risk for HPRT1 disorders immediately after birth in order to identify as early as possible those who would benefit from prompt initiation of xanthine oxidase inhibitors and anticipation of future needs.

评估 有风险的亲戚:

对HPRT1疾病有危险风险的男性在生后立即弄情检查这是适当的, 目的是尽早确诊那些病人, 并从马上启动黄嘌呤氧化酶抑制剂和预期未来需求的治疗中受益。

Genetic counseling 遗传咨询:

HPRT1 disorders are X linked.

The risk to sibs of a male proband depends on the genetic status of the mother. If the mother of the proband has an HPRT1 variant, the chance of transmitting it in each pregnancy is 50%: males who inherit a pathogenic HPRT1 variant will be affected. Females who inherit the pathogenic variant will be heterozygotes and will virtually always be clinically normal. If the proband represents a simplex case (i.e., a single occurrence in a family) and if the proband has a known HPRT1 variant that cannot be detected in his mother’s leukocyte DNA, the risk to sibs is low but greater than that of the general population because of the possibility of maternal mosaicism. Once an HPRT1 pathogenic variant has been identified in an affected family member, heterozygote testing for females and prenatal/preimplantation genetic testing are possible.




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