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Case Reports
. 2022 Jun 27;23(1):228.
doi: 10.1186/s12882-022-02851-2.

One case of arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome featuring an incomplete and mild phenotype

Lianhu Yu #  1 , Dan Li #  1 , Ting Zhang  1 , Yongmei Xiao  1 , Yizhong Wang  1 , Ting Ge  2
Affiliations
Case Reports

One case of arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome featuring an incomplete and mild phenotype

Lianhu Yu et al. BMC Nephrol. .

Abstract

Background: 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.

Case presentation: 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.

Conclusions: 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.

Keywords: ARC syndrome; Autosomal recessive disorder; Child; Compound heterozygote mutations; VPS33B.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Physical examination of the patient. A and B Deformities of finger and toe joints (claw-shaped). C Fish scale-like skin
Fig. 2
Fig. 2
Liver biopsy. A Haematoxylin–eosin (HE) staining (200X); B Cytokeratin 19 (CK19)-labelled tissues showed the absence of a bile duct (black arrow)
Fig. 3
Fig. 3
Electron microscopy of the liver tissue showed that the gross bile ducts were severely dilated
See this image and copyright information in PMC

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