alpha-methylacyl-CoA racemase deficiency

Alpha-Methylacyl-CoA Racemase Deficiency: A Rare Peroxisomal Disorder

Alpha-methylacyl-CoA racemase (AMACR) deficiency is a rare autosomal recessive peroxisomal disorder characterized by adult onset of variable neurodegenerative symptoms affecting the brain and nervous system [1][3][6]. This condition is also known as alpha-methylacyl-CoA racemase deficiency or AMACR deficiency.

Symptoms and Characteristics

People with AMACR deficiency may experience a gradual loss in intellectual functioning (cognitive decline), seizures, migraines, and other neurological symptoms [2]. The disorder can be considered as an adult slowly progressive disease with a predominant neurological phenotype [5].

• Neurological Symptoms: Cognitive decline, seizures, migraines, and other neurodegenerative symptoms are common in individuals with AMACR deficiency.
• Adult Onset: The condition typically manifests in adulthood, with variable age of onset.
• Rare Autosomal Recessive Disorder: AMACR deficiency is a rare genetic disorder inherited in an autosomal recessive pattern.

Bile Acid Synthesis Disorder

AMACR deficiency affects the body's ability to produce bile acids, which are essential for digestion and absorption of fats and fat-soluble vitamins [4]. This condition can be considered as a bile acid synthesis disorder.

• Bile Acid Synthesis: AMACR is involved in the beta-oxidation of branched-chain fatty acids, which is crucial for bile acid production.
• Impaired Bile Acid Production: The deficiency leads to impaired production of bile acids, affecting digestion and absorption of fats and fat-soluble vitamins.

Enzyme Involved

Alpha-methylacyl-CoA racemase (AMACR) is a mitochondrial and peroxisomal enzyme that catalyzes the conversion of 2R stereoisomers of phytanic and pristanic acids [9]. The deficiency affects this enzyme's function, leading to impaired bile acid production.

References

[1] AMACR deficiency is a rare autosomal recessive peroxisomal disorder characterized by adult onset of variable neurodegenerative symptoms affecting the brain and nervous system. [2] People with AMACR deficiency may have a gradual loss in intellectual functioning (cognitive decline), seizures, and migraines. [3] AMACR deficiency is a rare autosomal recessive peroxisomal disorder characterized by adult onset of variable neurodegenerative symptoms. [4] This is a bile acid synthesis disorder. This means it affects how your body produces bile acids. [5] by FCC Klouwer · 2024 — AMACR deficiency can be considered as an adult slowly progressive disease with a predominant neurological phenotype. [6] AMACR deficiency is a rare autosomal recessive peroxisomal disorder characterized by adult onset of variable neurodegenerative symptoms affecting the brain and nervous system. [7] Alpha-methylacyl-CoA-racemase gene product, also referred to as P504S protein, is an enzyme involved in beta-oxidation of branched chain fatty acids. [8] by K Haugarvoll · 2013 · Cited by 65 — Alpha-methylacyl-coA racemase deficiency presents heterogeneously in adults, with peripheral neuropathy, pigmentary retinopathy, seizures and ... [9] Alpha-methylacyl-CoA racemase (AMACR; EC 5.1.99.4) is a mitochondrial and peroxisomal enzyme that catalyzes the conversion of 2R stereoisomers of phytanic and pristanic acids.

Alpha-methylacyl-CoA racemase (AMACR) deficiency is a rare genetic disorder that affects the nervous system. The signs and symptoms of this condition can vary, but here are some common ones:

• Gradual decline in memory and thinking skills: This is one of the earliest signs of AMACR deficiency, where individuals may experience a gradual loss of intellectual functioning (cognitive decline) [1].
• Seizures: People with AMACR deficiency may have seizures, which can be a significant concern for their overall health [2].
• Migraines: Migraine is another common symptom associated with AMACR deficiency, where individuals may experience recurring headaches and other symptoms [3].
• Visual problems: Some people with AMACR deficiency may experience visual failure or other eye-related issues [4].
• Sensorimotor neuropathy: This condition can cause damage to the nerves that control movement and sensation, leading to weakness, numbness, or tingling in various parts of the body [5].
• Spasticity: Individuals with AMACR deficiency may experience muscle stiffness or spasms, which can be uncomfortable and affect their daily activities [6].

It's essential to note that these symptoms can vary from person to person, and not everyone with AMACR deficiency will exhibit all of them. If you're concerned about a specific symptom or condition, it's always best to consult with a healthcare professional for personalized advice.

References: [1] Dec 1, 2013 — People with AMACR deficiency may have a gradual loss in intellectual functioning (cognitive decline), seizures, and migraines. [2] Clinical features · Seizures [3] Features may include seizures, visual failure, sensorimotor neuropathy, spasticity, migraine, and white matter hyperintensities on brain imaging. Serum ... [4] by FCC Klouwer · 2024 — Most common neurological signs in our cohort were sensomotor axonal neuropathy, ataxia and cognitive decline without a history of cognitive ... [5] Table 2 Signs at presentation and during follow-up ; Nervous system · Psychiatric symptoms. 1 ; Nervous system · Stroke-like episode. 1 ; Vision. Retinitis ... [6] by FCC Klouwer · 2024 — AMACR deficiency can be considered as an adult slowly progressive disease with a predominant neurological phenotype. The main signs comprise ...

Diagnostic Tests for Alpha-Methylacyl-CoA Racemase Deficiency

Alpha-methylacyl-CoA racemase (AMACR) deficiency is a rare genetic disorder that can be diagnosed through various diagnostic tests. Here are some of the diagnostic tests used to diagnose AMACR deficiency:

• Mass Spectrometry: This test analyzes blood, bile, and urine samples to detect abnormalities in the levels of certain metabolites associated with AMACR deficiency [1][2].
• Exome Sequencing: This is a next-generation sequencing (NGS) test that can identify genetic mutations responsible for AMACR deficiency [3][4].
• Targeted Mutation Analysis: This test involves analyzing specific genes, including the AMACR gene, to detect mutations associated with the disorder [5].
• Mutation Scanning/Screening and Sequence Analysis of Selected Genes: This test is used to identify genetic mutations in selected genes, including the AMACR gene, that may be responsible for the disorder [6].

These diagnostic tests can help confirm a diagnosis of AMACR deficiency, which is essential for providing appropriate medical care and management.

References:

[1] Context 4 [2] Context 1 [3] Context 7 [4] Context 9 [5] Context 6 [6] Context 8

Treatment Options for Alpha-Methylacyl-CoA Racemase Deficiency

Alpha-methylacyl-CoA racemase (AMACR) deficiency is a rare genetic disorder that requires specialized treatment. Based on the available information, here are some potential drug treatment options:

• Primary Bile Acid Therapy: This therapy involves administering cholic acid to patients with AMACR deficiency. According to [5], primary bile acid therapy can help normalize liver enzymes and prevent neurologic symptoms in infants.
• Dietary Exclusion of Phytanic and Pristanic Acid: Dietary exclusion of these acids may offer a potential long-term treatment for AMACR deficiency, as suggested by [2].
• Cholic Acid Therapy: This therapy is effective in treating the liver disease associated with AMACR deficiency. According to [9], cholic acid therapy can help manage the condition.

It's essential to note that these treatment options may vary depending on individual patient needs and circumstances. Consultation with a medical professional or a specialist in genetic disorders is necessary for accurate diagnosis and effective treatment planning.

References:

• [5] Primary bile acid therapy with CA is effective in normalizing liver enzymes and preventing the onset of neurologic symptoms in the infant coupled with dietary ...
• [9] Alpha-methyl-acyl-CoA racemase deficiency; BASD4; Liver disease-retinitis ... Treatment is based on primary bile acid therapy with cholic acid. Dietary ...
• [2] by SA Thompson · 2009 · Cited by 59 — Dietary exclusion of phytanic and pristanic acid offers a potential long term treatment for this condition. ...

Differential Diagnosis of Alpha-Methylacyl-CoA Racemase Deficiency

Alpha-methylacyl-CoA racemase (AMACR) deficiency is a rare autosomal recessive peroxisomal disorder that can be challenging to diagnose. The differential diagnosis for AMACR deficiency involves considering various clinical features and laboratory findings.

Clinical Features:

• Neonatal cholestasis
• Late-onset sensorimotor neuropathy
• Relapsing encephalopathy
• Cerebellar ataxia, particularly with seizures or recurrent encephalopathic episodes

These clinical features can mimic other conditions such as Refsum disease, and therefore, a comprehensive diagnostic approach is necessary.

Laboratory Findings:

• Accumulation of pristanic acid and 16:1ω5 fatty acid in plasma and tissues
• Elevated levels of very-long-chain fatty acids (VLCFAs) in plasma

These laboratory findings can help differentiate AMACR deficiency from other peroxisomal disorders.

Differential Diagnosis:

• Refsum disease
• Acyl-CoA-oxidase deficiency
• Other peroxisomal disorders, such as Zellweger syndrome and rhizomelic lipodystrophy

Considering the clinical features and laboratory findings of AMACR deficiency is essential for accurate diagnosis. A thorough evaluation by a multidisciplinary team of healthcare professionals, including geneticists, neurologists, and pathologists, can help establish a definitive diagnosis.

References:

• [8] Alpha-methylacyl-CoA-racemase (AMACR) deficiency (MIM#604489) is a rare autosomal recessive peroxisomal disorder.
• [10] Alpha-methyl acyl-CoA racemase deficiency (AMACRD) is a rare peroxisomal disorder that results in the accumulation of pristanic acid and 16:1ω5 fatty acid.
• [9] We strongly agree with Dr. Schon and Prof. Chinnery that alpha-methylacyl-CoA racemase (AMACR) deficiency should be considered in the differential diagnosis of cerebellar ataxia, particularly with seizures or recurrent encephalopathic episodes.