arthrogryposis, renal dysfunction, and cholestasis 1

Arthrogryposis-Renal Dysfunction-Cholestasis (ARC) Syndrome

ARC syndrome is a rare genetic disorder characterized by congenital joint contractures, renal tubular dysfunction, and neonatal cholestasis with low serum gamma-glutamyl transferase activity. This multisystem disorder affects multiple organs and systems in the body.

Key Features:

• Congenital Joint Contractures: Also known as arthrogryposis multiplex congenita, this feature is characterized by bent or contracted limbs that are difficult to straighten.
• Renal Tubular Dysfunction: This involves impaired kidney function, leading to various complications such as renal tubular acidosis and Fanconi syndrome.
• Neonatal Cholestasis: A condition where the bile ducts are blocked, causing a buildup of bile in the liver and potentially leading to liver damage.
• Low Serum Gamma-Glutamyl Transferase (GGT) Activity: GGT is an enzyme that helps break down proteins. Low levels of this enzyme can indicate liver or kidney problems.

Causes and Inheritance:

ARC syndrome is caused by genetic mutations, specifically in the VPS33B gene on chromosome 15q26.1. These mutations can be inherited from parents or occur randomly during cell division. The condition is autosomal recessive, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the syndrome.

Prognosis:

Unfortunately, ARC syndrome has a high mortality rate, and most patients do not survive past the first year of life [13][14]. Early diagnosis and treatment are crucial for managing symptoms and improving quality of life.

References: [1] - Description of arthrogryposis, renal dysfunction, and cholestasis-1 (ARCS1) is characterized by congenital joint contractures, renal tubular dysfunction, cholestasis with low GGT activity, severe failure to thrive, ichthyosis, and a defect in platelet alpha-granule biogenesis. ... Mutations in VPS33B gene on chromosome 15q26.1. [10] - Description of arthrogryposis-Renal dysfunction-Cholestasis (ARC) syndrome is a multisystem disorder, characterized by neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and neonatal cholestasis with low serum gamma-glutamyl transferase activity. [13] - Most patients with ARC do not survive past the first year of life (Gissen et al., 2006; Smith et al., 2012). [14] - ARC (arthrogryposis, renal dysfunction, cholestasis) is a clinical syndrome with multisystem disorder, the major presentations are arthrogryposis, renal tubular dysfunction and cholestasis.

Common Signs and Symptoms of Arthrogryposis, Renal Dysfunction, and Cholestasis (ARC) Syndrome

People with ARC syndrome typically exhibit a range of symptoms that affect multiple systems in the body. The classical presentation of ARC includes:

• Congenital joint contractures: This is one of the hallmark features of ARC, where joints are stiff or rigid from birth.
• Renal tubular dysfunction: This refers to the kidneys' inability to remove acids from the blood into the urine, leading to various complications.
• Cholestasis with low GGT activity: Cholestasis is a condition where bile flow is reduced or blocked, and in ARC, it's often associated with low gamma-glutamyl transferase (GGT) activity.

In addition to these primary symptoms, people with ARC may also experience:

• Severe failure to thrive: This refers to a significant delay in growth and development.
• Ichthyosis: A condition characterized by dry, scaly skin.
• Abnormal platelet count and function: Platelets play a crucial role in blood clotting, and abnormalities can lead to bleeding or clotting disorders.
• Secondary infection: People with ARC are more susceptible to infections due to their compromised immune system.

These symptoms can vary in severity and may be present at birth or develop later in life. Early diagnosis and treatment are essential for managing the condition effectively.

References:

• [1] Arthrogryposis, renal dysfunction, and cholestasis-1 (ARCS1) is characterized by congenital joint contractures, renal tubular dysfunction, cholestasis with low GGT activity... (Source: #2)
• [2] The classical presentation of ARC includes congenital joint contractures, renal tubular dysfunction, and cholestasis. Additional features include ichthyosis, abnormal platelet count and function, secondary infection, and ... (Source: #9)
• [3] Arthrogryposis-Renal dysfunction-Cholestasis syndrome (ARC) is a rare multisystem disease due to mutations in the VPS33B and VIPAR genes... In summary, our patient presented with all of the characteristic signs and symptoms of ARC (summarized in Table ...). (Source: #15)
• [4] ARC syndrome typically presents with arthrogryposis, renal tubular leak and neonatal cholestatic jaundice, and most patients with this disease have severe failure to thrive. (Source: #12)

Diagnostic Tests for Arthrogryposis, Renal Dysfunction, and Cholestasis (ARC) Syndrome

The diagnosis of ARC syndrome can be made through various diagnostic tests. Here are some of the key tests used to diagnose this condition:

• Laboratory tests: These include tests to evaluate kidney function, liver function, and electrolyte levels. For example, a test for renal tubular acidosis may be performed to assess kidney function (Source: [2]).
• Imaging studies: Imaging studies such as ultrasound or MRI may be used to evaluate the musculoskeletal system, kidneys, and liver.
• Genetic testing: Genetic testing can be done to identify mutations in the VPS33B gene, which is associated with ARC syndrome. This test can help confirm the diagnosis (Source: [7], [8]).
• Deletion/duplication analysis: This test can also be used to identify deletions or duplications of genes that may be associated with ARC syndrome.
• Mutation scanning: This test can be used to scan for mutations in specific genes, including the VPS33B gene.

It's worth noting that a diagnosis of ARC syndrome is typically made based on a combination of clinical findings and laboratory results. A healthcare professional will use these tests to rule out other conditions and confirm the diagnosis (Source: [3]).

References

[1] Source: [2] [2] Diagnostic tests Laboratories; Diagnostic tests ... Arthrogryposis-renal dysfunction-cholestasis syndrome. [3] A number sign (#) is used with this entry because arthrogryposis, renal dysfunction, and cholestasis-1 (ARCS1) ... [7] Any arthrogryposis-renal dysfunction-cholestasis syndrome in which the cause of the disease is a mutation in the VPS33B gene. [8] by R Rehman · 2024 · Cited by 1 — Arthrogryposis renal dysfunction cholestasis.

Treatment Overview

The treatment of Arthrogryposis-Renal Dysfunction-Cholestasis (ARC) syndrome is mainly symptomatic and targeted towards preventing significant liver and renal injury. Unfortunately, there is no specific treatment for the disease, and most patients die within the first year of life despite supportive care for metabolic acidosis and cholestasis [2].

Management Strategies

In some cases, external applications such as triamcinolone acetonide econazole cream and urea ointment may be used to relieve ichthyosis [4]. Additionally, opiate antagonist therapy has been explored as a treatment option for the pruritus associated with cholestasis, although it requires careful management to avoid opioid withdrawal symptoms [8].

Current Research

Recent studies have focused on identifying genetic variants associated with ARC syndrome. A case series published in 2024 adds to the spectrum of ARC-associated variants, highlighting the need for further research into the underlying causes and potential treatments for this condition [10].

Gene Therapy

Unfortunately, there is currently no gene therapy available for the treatment of ARC syndrome [6]. Treatment options are limited, and supportive care remains the primary approach.

Consult a Healthcare Professional

It's essential to consult with a healthcare professional for medical advice and treatment. They can provide personalized guidance based on individual circumstances and help manage symptoms effectively.

References: [2] - There is no specific treatment for the disease. Most patients die within the first year of life despite supportive care for metabolic acidosis and cholestasis ... [4] by L Yu · 2022 · Cited by 1 — External applications of triamcinolone acetonide econazole cream and urea ointment were used to relieve ichthyosis. Fortunately, the patient's ... [6] by R Rehman · 2024 · Cited by 1 — Treatment of ARC syndrome is mainly symptomatic and targeted toward preventing significant liver and renal injury. There is no gene therapy ... [8] by R Gamal · 2018 — Arthrogryposis-renal dysfunction-cholestasis ... Opiate antagonist therapy for the pruritus of cholestasis: the avoidance of opioid withdrawal‐ ... [10] May 1, 2024 — This current case series adds to the spectrum of Arthrogryposis renal dysfunction cholestasis (ARC)-associated variants.