ABHD12

ABHD12, also known as α/β-Hydrolase Domain-Containing Protein 12, is an enzyme that plays a key role in lipid metabolism and maintaining neuroinflammatory balance. 

Research into ABHD12 has increased due to its connection to neurodegenerative diseases such as PHARC syndrome (Polyneuropathy, Hearing Loss, Ataxia, Retinitis Pigmentosa, and Cataract), and its potential therapeutic applications in treating lipid metabolism disorders.

What is ABHD12?

ABHD12 is a gene that encodes an enzyme responsible for breaking down 2-arachidonoyl glycerol (2-AG), an important cannabinoid in the body's endocannabinoid system, and lysophosphatidylserine, an important phospholipid. 

ABHD12 is found in many tissues, including the thyroid, brain, and immune cells, where it plays a key role in maintaining normal body functions.

Mutations in ABHD12 are associated with the rare disease PHARC syndrome. PHARC syndrome causes issues like neuropathy, hearing loss, and vision problems. 

ABDH12, the Endocannabinoid System, and 2-AG

The endocannabinoid system (ECS) is a complex network that regulates various functions like mood, appetite, pain, and inflammation. It consists of endocannabinoids, receptors (CB1 and CB2), and enzymes that control their production and breakdown. 

The ECS affects memory, learning, and synaptic plasticity and helps modulate how the body responds to stress and injury. 

2-arachidonoyl glycerol (2-AG) is an endocannabinoid that acts on cannabinoid receptors to regulate various physiological processes. Because the ABHD12 enzyme helps break down 2-AG, mutations in the ABHD12 gene can lead to a buildup of 2-AG, contributing to neurodegenerative diseases like PHARC syndrome by disrupting normal endocannabinoid metabolism and signaling over time.

ABHD12 and Lysophosphatidylserine

The enzyme ABHD12 helps control lipid metabolism, particularly by breaking down a type of lipid called lysophosphatidylserine (lysoPS). LysoPS is involved in inflammation and the immune response, and ABHD12 helps keep its levels balanced. 

When ABHD12 doesn't work properly, as seen in diseases like PHARC syndrome, lysoPS can build up. The buildup of lysoPS is associated with neuroinflammation and neurobehavioural abnormalities, which may be related to the development of neurodegenerative diseases, including PHARC syndrome. 

Unlike 2-AG, an endocannabinoid that affects the brain and body by interacting with cannabinoid receptors, lysoPS doesn't work in the same way. Instead, lysoPS mainly controls immune reactions and inflammation, differentiating it from 2-AG's role in the body.

As interest in lipid dysregulation and neuroinflammation grows, ABHD12 has become a valued biomarker for neurodegenerative conditions.

PHARC Syndrome

PHARC syndrome is very rare, with the first case diagnosed in 2009 and less than 40 cases reported. 

PHARC syndrome (Polyneuropathy, Hearing Loss, Ataxia, Retinitis Pigmentosa, and Cataract) is an autosomal recessive genetic neurodegenerative disorder caused by mutations in the ABHD12 gene. This condition typically leads to progressive neurological issues such as polyneuropathy, hearing loss, vision problems, and balance difficulties. 

PHARC is often misdiagnosed because its symptoms overlap with other disorders, including mitochondrial diseases and Charcot-Marie-Tooth disease. 

The disorder is inherited in an autosomal recessive manner, and its symptoms can vary widely, making diagnosis challenging. 

Symptoms often appear in the third decade of life due progressive peripheral neuropathy.

Who Should Get ABHD12 Tested?

The following groups may consider getting their ABHD12 status tested: 

Individuals with Genetic Risk Factors

Testing for ABHD12 is valuable for individuals with a family history of PHARC syndrome or related genetic disorders. 

Genetic testing can help identify individuals at risk and provide an early diagnosis, essential for starting treatment sooner and managing the condition effectively.

Patients Exhibiting Neurological Symptoms

Patients experiencing symptoms like progressive neuropathy, hearing or vision loss, or ataxia should consider ABHD12 testing. 

These symptoms may signal a neurodegenerative disorder, and identifying the underlying cause through biomarker testing allows for better diagnosis and treatment planning.

Medical Researchers and Drug Development

ABHD12 testing is also vital in research. It helps explore new therapies for conditions linked to neuroinflammation, lipid metabolism, and neurodegeneration, particularly in clinical trials for multiple sclerosis and other related diseases.

Genetic Testing 

Genetic testing involves analyzing a person's DNA to identify specific mutations or genetic variations that may be linked to health conditions or diseases. This testing typically requires a sample of DNA, which can be obtained through blood, saliva, or cheek swabs. 

Once the sample is collected, it is processed in a laboratory to identify variations, such as single nucleotide polymorphisms (SNPs), that could impact a person’s health. Genetic testing is often used to assess disease risk, predict drug responses, and inform personalized treatment plans. 

Before testing, it’s essential to consult with a healthcare provider to understand the purpose and implications of the test.

Genetic Testing for ABHD12

Genetic testing for ABHD12 may be considered in individuals showing neurological symptoms such as progressive neuropathy, hearing or vision loss, or ataxia. 

Testing a person's ABHD12 genetic status helps identify mutations linked to PHARC syndrome and similar neurodegenerative conditions, allowing for early diagnosis and more effective management. It’s especially useful for those with a family history of these disorders. 

Test ordering and interpretation are generally handled by a specialist; individuals with questions about this testing should consult a medical professional for more information.

By identifying mutations in the ABHD12 gene, healthcare providers can offer targeted treatments and better understand the underlying causes of the symptoms. 

Order Genetic Testing

Click here to compare genetic test panels and order genetic testing for health-related SNPs.