Abstract：
Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare disease with a high mortality rate caused by VPS33B or VIPAS39 mutations. ARC syndrome typically presents with arthrogryposis, renal tubular leak and neonatal cholestatic jaundice, and most patients with this disease do not survive beyond one year.
Here, we report the case of a 13-year-old girl with ARC featuring an incomplete and mild phenotype with novel compound heterozygous mutations of VPS33B. The patient presented with arthrogryposis (claw-shaped limbs), ichthyosis, jaundice, and pruritus. Laboratory tests revealed highly evaluated levels of total bilirubin (TB), direct bilirubin (DB), and total bile acid (TBA) as well as normal levels of gamma-glutamyltransferase (GGT). However, signs of renal dysfunction, as well as other manifestations of ARC syndrome, including nervous system abnormalities, deafness, and failure to thrive, were not observed. The patient\'s clinical symptoms of jaundice and pruritus were significantly alleviated by administration of ursodeoxycholic acid. Whole-exome sequencing (WES) revealed novel compound heterozygous mutations of VPS33B, c.1081 C > T (p.Q361X,257)/c.244 T > C (p.C82R). Both variants were predicted to be pathogenic in silico and have never been reported previously. To date, the patients\' cholestatic jaundice has been well controlled with continuous treatment of ursodeoxycholic acid.
We report the case of a Chinese female with ARC including novel compound heterozygous mutations of VPS33B and an incomplete and mild phenotype. Early diagnosis and suitable symptomatic therapies are critical for the management of ARC patients with mild manifestations and prolonged lifespan.
Here, we report the case of a 13-year-old girl with ARC featuring an incomplete and mild phenotype with novel compound heterozygous mutations of VPS33B. The patient presented with arthrogryposis (claw-shaped limbs), ichthyosis, jaundice, and pruritus. Laboratory tests revealed highly evaluated levels of total bilirubin (TB), direct bilirubin (DB), and total bile acid (TBA) as well as normal levels of gamma-glutamyltransferase (GGT). However, signs of renal dysfunction, as well as other manifestations of ARC syndrome, including nervous system abnormalities, deafness, and failure to thrive, were not observed. The patient\'s clinical symptoms of jaundice and pruritus were significantly alleviated by administration of ursodeoxycholic acid. Whole-exome sequencing (WES) revealed novel compound heterozygous mutations of VPS33B, c.1081 C > T (p.Q361X,257)/c.244 T > C (p.C82R). Both variants were predicted to be pathogenic in silico and have never been reported previously. To date, the patients\' cholestatic jaundice has been well controlled with continuous treatment of ursodeoxycholic acid.
We report the case of a Chinese female with ARC including novel compound heterozygous mutations of VPS33B and an incomplete and mild phenotype. Early diagnosis and suitable symptomatic therapies are critical for the management of ARC patients with mild manifestations and prolonged lifespan.
摘要：
关节-肾功能障碍-胆汁淤积（ARC）综合征是一种罕见的疾病，由VPS33B或VIPAS39突变引起的高死亡率。ARC综合征通常表现为关节病，肾小管渗漏和新生儿胆汁淤积性黄疸，大多数患有这种疾病的患者无法生存超过一年。
这里,我们报道了1例13岁的ARC患者,其表型不完全且轻度,有VPS33B的新型复合杂合突变.患者出现关节病（爪形四肢），鱼鳞病,黄疸,还有瘙痒.实验室测试显示，总胆红素（TB）的评估水平很高，直接胆红素（DB），和总胆汁酸（TBA）以及正常水平的γ-谷氨酰转移酶（GGT）。然而,肾功能不全的迹象，以及ARC综合征的其他表现，包括神经系统异常,耳聋,未能茁壮成长，没有被观察到。应用熊去氧胆酸可明显缓解患者黄疸和瘙痒的临床症状。全外显子组测序（WES）揭示了VPS33B的新型复合杂合突变，c.1081C>T（p。Q361X,257）/c.244T>C（p。C82R)。预测这两种变体在计算机上都是致病性的，以前从未报道过。迄今为止,熊去氧胆酸连续治疗后胆汁淤积性黄疸得到良好控制。
我们报道了一例中国女性ARC，包括VPS33B的新型复合杂合突变和不完全和轻度表型。早期诊断和适当的对症治疗对于治疗轻度表现和延长寿命的ARC患者至关重要。
这里,我们报道了1例13岁的ARC患者,其表型不完全且轻度,有VPS33B的新型复合杂合突变.患者出现关节病（爪形四肢），鱼鳞病,黄疸,还有瘙痒.实验室测试显示，总胆红素（TB）的评估水平很高，直接胆红素（DB），和总胆汁酸（TBA）以及正常水平的γ-谷氨酰转移酶（GGT）。然而,肾功能不全的迹象，以及ARC综合征的其他表现，包括神经系统异常,耳聋,未能茁壮成长，没有被观察到。应用熊去氧胆酸可明显缓解患者黄疸和瘙痒的临床症状。全外显子组测序（WES）揭示了VPS33B的新型复合杂合突变，c.1081C>T（p。Q361X,257）/c.244T>C（p。C82R)。预测这两种变体在计算机上都是致病性的，以前从未报道过。迄今为止,熊去氧胆酸连续治疗后胆汁淤积性黄疸得到良好控制。
我们报道了一例中国女性ARC，包括VPS33B的新型复合杂合突变和不完全和轻度表型。早期诊断和适当的对症治疗对于治疗轻度表现和延长寿命的ARC患者至关重要。
