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Disease Profile

Arthrogryposis renal dysfunction cholestasis syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Neonatal

ICD-10

Q89.7

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

ARC syndrome; Arthrogryposis multiplex congenita, renal dysfunction, and cholestasis; Arthrogryposis renal dysfunction cholestasis;

Categories

Congenital and Genetic Diseases; Digestive Diseases; Eye diseases;

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
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Orpha Number: 2697

Definition
A rare, multisystem disorder, characterized by neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and neonatal cholestasis with low serum gamma-glutamyl transferase activity.

Epidemiology
The prevalence is unknown but less than 100 patients have been reported in the literature so far.

Clinical description
The phenotype is variable, even within the same family and cases may go undiagnosed as not all the patients present with the three cardinal features. Renal tubular dysfunction ranges from isolated renal tubular acidosis to complete Fanconi syndrome (polyuria, aminoaciduria, glycosuria, phosphaturia and bicarbonate wasting). Hepatic anomalies include variable combinations of cholestasis, intrahepatic biliary duct hypoplasia and lipofuscin deposition. Additional features include severe failure to thrive, platelet dysfunction (which may be responsible for severe bleeding), facial dysmorphism (low set ears, lax skin, a high arched palate, beaked nose and small anterior fontanelle), diarrhea, recurrent febrile illness, cerebral malformations and sensorineural deafness.

Etiology
Mutations in the VPS33B gene (15q26.1), involved in intracellular protein trafficking and membrane fusion, have been found in 75% of ARC families, as well as mutations in the VIPAR gene (C14ORF133), encoding a protein that complexes with VPS33B.

Differential diagnosis
The differential diagnosis should include progressive familial intrahepatic cholestasis disorders, other forms of arthrogryposis multiplex congenita and congenital ichthyosiform dermatoses (see these terms).

Genetic counseling
The syndrome is generally considered to be transmitted as an autosomal recessive trait.

Management and treatment
There is no specific treatment for the disease.

Prognosis
Most patients die within the first year of life despite supportive care for metabolic acidosis and cholestasis and those surviving longer show cirrhosis and severe developmental delay.

Visit the Orphanet disease page for more resources.

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) lists the subtypes and associated genes for Arthrogryposis renal dysfunction cholestasis syndrome in a table called Phenotypic Series. Each entry in OMIM includes a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Arthrogryposis renal dysfunction cholestasis syndrome. Click on the link to view a sample search on this topic.