Novel gene mutations in three Japanese patients with ARC syndrome associated mild phenotypes: a case series

Journal of Medical Case Reports

Masanao Yano¹  Shogo Ito²  Takao Togawa²  Yoshinori Satomura³  Yuki Yamano³  Kazuhiko Bessho³  Shin Nabatame³  Keiichi Ozono³  Taisuke Inoue³  Taichi Kitaoka³  Tomoya Fukuoka³  Takeshi Kimura³  Makiko Tachibana³  Nobutoshi Nawa³  Shinsuke Onuma³  Hidehito Kondo³  Kie Yasuda³  Miho Fukui³ 

[1] Department of General Pediatrics, Osaka Women’s and Children’s Hospital, Osaka, Japan;Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan;Department of Pediatrics, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan;

关键词: ARC syndrome;    VPS33B;    VIPAS39;    Targeted NGS;    Neonatal cholestasis;    Mild phenotype;    Normal GGT;    Severe hemorrhage;   

DOI  :  10.1186/s13256-022-03279-w

来源: Springer

【 摘 要 】

BackgroundArthrogryposis, renal dysfunction, and cholestasis syndrome (ARCS) is a rare autosomal recessive disorder caused by mutations in VPS33B (ARCS1) and VIPAS39 (ARCS2). As per literature, most patients with ARCS died of persistent infections and bleeding by the age of 1 year. We report the first Japanese cases with ARCS1 and ARCS2 who presented with mild phenotypes and were diagnosed via genetic testing.Case presentationCase 1: A 6-year-old boy born to nonconsanguineous Japanese parents presented with jaundice and normal serum gamma-glutamyl transferase (GGT) levels, proteinuria, bilateral nerve deafness, motor delay, failure to thrive, and persistent pruritus. After cochlear implantation for deafness at the age of 2 years, despite a normal platelet count and prothrombin time-international normalized ratio, the patient presented with persistent bleeding that required hematoma removal. Although he did not show any obvious signs of arthrogryposis, he was suspected to have ARCS based on other symptoms. Compound heterozygous mutations in VPS33B were identified using targeted next-generation sequencing (NGS), which resulted in no protein expression. Case 2: A 7-month-old boy, the younger brother of case 1, presented with bilateral deafness, renal tubular dysfunction, failure to thrive, and mild cholestasis. He had the same mutations that were identified in his brother’s VPS33B. Case 3: A 24-year-old man born to nonconsanguineous Japanese parents was suspected to have progressive familial intrahepatic cholestasis 1 (PFIC1) in his childhood on the basis of low GGT cholestasis, renal tubular dysfunction, sensory deafness, mental retardation, and persistent itching. A liver biopsy performed at the age of 16 years showed findings that were consistent with PFIC1. He developed anemia owing to intraperitoneal hemorrhage from a peripheral intrahepatic artery the day after the biopsy, and transcatheter arterial embolization was required. ARCS2 was diagnosed using targeted NGS, which identified novel compound heterozygous mutations in VIPAS39.ConclusionsThe first Japanese cases of ARCS1 and ARCS2 diagnosed using genetic tests were reported in this study. These cases are milder than those previously reported. For patients with ARCS, invasive procedures should be performed with meticulous care to prevent bleeding.

【 授权许可】

CC BY