ARC syndrome

Classification according to ICD-10
Q 89.7	Multiple congenital malformations, not elsewhere classified
ICD-10 online (WHO version 2019)

The ARC syndrome , acronym for A rthrogryposis multiplex congenita , R enal dysfunction and C holestasis , is a very rare congenital disease with the main characteristics of congenital joint stiffness, kidney dysfunction and biliary congestion.

Synonyms are: arthrogryposis - renal dysfunction - cholestasis

The first description comes from 1979 by the French pathologist C. Nezelof and colleagues.

However, AR Lutz-Richner and RF Landolt had already described a combination of familial bile duct malformation and tubular renal insufficiency as early as 1973.

distribution

The frequency is given as less than 1 in 1,000,000, so far fewer than 100 people have been reported. Inheritance is autosomal - recessive .

root cause

Depending on the underlying mutation , the following types can be distinguished:

Type 1 , in 75% of families, mutations in the VPS33B - gene on chromosome 15 locus is involved q26.1 that the intracellular protein transport and membrane fusion
Type 2 , mutations in the VIPAS39 gene on chromosome 14 locus q24.3

Clinical manifestations

Clinical criteria are:

Manifestation in newborn or childhood
Renal dysfunction from isolated renal tubular acidosis to Fanconi syndrome
decreased activity of gammaglutamyl transferase in the blood serum

Liver changes with cholestasis, biliary atresia , deposition of lipofuscin

Pronounced failure to thrive

Bleeding due to a dysfunction of platelets

Facial abnormalities, deep-seated ears, sagging skin, high palatal arch, beak-shaped nose, small anterior fontanel

recurrent fever and diarrhea

accompanying brain malformations and sensorineural hearing loss

Differential diagnosis

The following are to be distinguished:

Byler syndrome (familial progressive intrahepatic cholestasis)
other forms of arthrogryposis multiplex congenita

therapy

Only symptomatic treatment of metabolic acidosis and cholestasis is currently possible. Many sufferers die in their first year of life or develop cirrhosis of the liver.

literature

M. Mutlu, Y. Aslan, F. Aktürk-Acar, M. Çakır, E. Erduran, M. Kalyoncu: ARC syndrome. In: The Turkish journal of pediatrics. Volume 59, number 4, 2017, pp. 487-490, doi: 10.24953 / turkjped.2017.04.019 , PMID 29624233 .
A. Giraud, F. Ramond, C. Cremillieux, R. Touraine, H. Patural, JL Stephan: Le phenotype complexe du syndrome ARC: une nouvelle observation. In: Archives de pediatrie: organe officiel de la Societe francaise de pediatrie. Volume 24, number 2, February 2017, pp. 131-134, doi: 10.1016 / j.arcped.2016.11.004 , PMID 28007512 .
MA Akbar, R. Mandraju, C. Tracy, W. Hu, C. Pasare, H. Krämer: ARC Syndrome-Linked Vps33B Protein Is Required for Inflammatory Endosomal Maturation and Signal Termination. In: Immunity. Volume 45, number 2, 08 2016, pp. 267-279, doi: 10.1016 / j.immuni.2016.07.010 , PMID 27496733 , PMC 4988897 (free full text).
V. Velmishi, E. Dervishi, D. Bali, A. Shehu, P. Cullufi: Constipation as an Atypical Sign of ARC Syndrome - Case Report. In: Current health sciences journal. Volume 42, number 2, 2016 Apr-Jun, pp. 203-206, doi: 10.12865 / CHSJ.42.02.13 , PMID 30568833 , PMC 6256161 (free full text).
A. Elmeery, K. Lanka, J. Cummings: ARC syndrome in preterm baby. In: Journal of perinatology: official journal of the California Perinatal Association. Volume 33, number 10, October 2013, pp. 821-822, doi: 10.1038 / jp.2013.62 , PMID 24071963 .
J. Denecke, KP Zimmer, R. Kleta, HG Koch, H. Rabe, C. August, E. Harms: Arthrogryposis, renal tubular dysfunction, cholestasis (ARC) syndrome: case description and literature review. In: Clinical Pediatrics. Volume 212, Number 2, 2000 Mar-Apr, pp. 77-80, doi: 10.1055 / s-2000-9656 , PMID 10812557 .

Individual evidence

↑ ^a ^b ^c arthrogryposis - renal dysfunction - cholestasis. In: Orphanet (Rare Disease Database).
↑ C. Nezelof, MC Dupart, F. Jaubert, E. Eliachar: A lethal familial syndrome associating arthrogryposis multiplex congenita, renal dysfunction, and a cholestatic liver disease and pigmentary. In: The Journal of pediatrics. Volume 94, Number 2, February 1979, pp. 258-260, PMID 762621 .
^ A. R Lutz-Richner, RF Landolt: Familiaere bile duct malformations with tubular renal insufficiency. In: Helv. Pediat. Acta , Vol. 28, 1973, pp. 1-12
^ Arthrogryposis, renal dysfunction, and cholestasis 1. In: Online Mendelian Inheritance in Man . (English)
^ Arthrogryposis, renal dysfunction, and cholestasis 2. In: Online Mendelian Inheritance in Man . (English)

[Orpha-1] arthrogryposis - renal dysfunction - cholestasis. In: Orphanet (Rare Disease Database).

[2] C. Nezelof, MC Dupart, F. Jaubert, E. Eliachar: A lethal familial syndrome associating arthrogryposis multiplex congenita, renal dysfunction, and a cholestatic liver disease and pigmentary. In: The Journal of pediatrics. Volume 94, Number 2, February 1979, pp. 258-260, PMID 762621 .

[3] A. R Lutz-Richner, RF Landolt: Familiaere bile duct malformations with tubular renal insufficiency. In: Helv. Pediat. Acta , Vol. 28, 1973, pp. 1-12

[4] Arthrogryposis, renal dysfunction, and cholestasis 1. In: Online Mendelian Inheritance in Man . (English)

[5] Arthrogryposis, renal dysfunction, and cholestasis 2. In: Online Mendelian Inheritance in Man . (English)