carnitine-acylcarnitine translocase deficiency

Common Signs and Symptoms of Carnitine-Acylcarnitine Translocase Deficiency

Carnitine-acylcarnitine translocase (CACT) deficiency is a rare inherited disorder that affects the body's ability to break down certain fats for energy. The signs and symptoms of this condition can vary in severity, but they often begin soon after birth.

Common Symptoms:

• Breathing problems
• Seizures
• Irregular heartbeat (arrhythmia)
• Lethargy
• Irritability
• Poor appetite
• Fever
• Diarrhea

These symptoms can be present at birth or may develop within the first few hours of life. In some cases, the signs and symptoms may not appear until later in infancy.

Other Possible Symptoms:

• Extremely low levels of ketones (products of fat breakdown that are used for energy)
• Low blood sugar (hypoglycemia)
• Cardiomyopathy (heart muscle disease)
• Hepatic dysfunction (liver problems)
• Skeletal muscle weakness
• Encephalopathy (brain damage)

It's essential to note that the severity and presentation of symptoms can vary widely among individuals with CACT deficiency.

References:

• [1] Signs and symptoms of this disorder usually begin soon after birth and may include breathing problems, seizures, and an irregular heartbeat (arrhythmia).
• [8] Signs and symptoms of this disorder usually begin soon after birth and may include breathing problems, seizures, and an irregular heartbeat (arrhythmia).
• [11] The signs of carnitine-acylcarnitine translocase deficiency usually begin within the first few hours of life. Seizures, an irregular heartbeat, and breathing problems are often the first signs of this disorder.
• [12] From MedlinePlus Genetics Carnitine-acylcarnitine translocase (CACT) deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). Signs and symptoms of this disorder usually begin soon after birth and may include breathing problems, seizures, and an irregular heartbeat (arrhythmia).
• [15] The signs of carnitine-acylcarnitine translocase (CACT) deficiency usually begin within the first few hours after birth. Seizures, an irregular heartbeat (), and breathing problems are often the first signs of the deficiency.It may also present with extremely low level of ketones (which are products of fat breakdown that are used for energy) and with low blood sugar (hypoglycemia).

Diagnostic Tests for Carnitine-Acylcarnitine Translocase Deficiency

Carnitine-acylcarnitine translocase (CACT) deficiency is a rare inherited fatty acid oxidation disorder that can be diagnosed through various diagnostic tests. Here are some of the common diagnostic tests used to diagnose CACT deficiency:

• Blood Tests: Blood tests can help detect low levels of carnitine and high levels of acylcarnitines in the blood, which are characteristic of CACT deficiency [5][7].
• Urine Tests: Urine tests may also be performed to detect abnormal levels of carnitine and acylcarnitines in the urine [5].
• Genetic Testing: Genetic testing can confirm a diagnosis of CACT deficiency by identifying mutations in the SLC25A20 gene, which codes for the CACT protein [4][12].
• Skin Biopsy: A skin biopsy may be performed to demonstrate reduced carnitine transport in fibroblasts, confirming a diagnosis of primary carnitine deficiency, including CACT deficiency [9].

Additional Diagnostic Tests

Other diagnostic tests that may be used to diagnose CACT deficiency include:

• Acylcarnitine Analysis: This test measures the levels of acylcarnitines in the blood or urine and can help confirm a diagnosis of CACT deficiency [13][14].
• Newborn Screening: Newborn screening programs may also detect CACT deficiency through blood tests, which measure the levels of carnitine and acylcarnitines in newborns [6][15].

References

[1] Carnitine-acylcarnitine translocase (CACT) is a critical component of the carnitine shuttle, which facilitates the transfer of long-chain fatty acylcarnitines across the inner mitochondrial membrane. CACT deficiency causes a defect in mitochondrial long-chain fatty acid β-oxidation, with variable clinical severity.

[2] Carnitine, a natural substance acquired mostly through the diet, is used by cells to process fats and produce energy. People with this disorder have a faulty transporter (CACT) that disrupts fatty acid oxidation.

[3] Systemic primary carnitine deficiency (CDSP) is a disorder of the carnitine cycle that results in defective fatty acid oxidation. Diagnosis/testing. Plasma carnitine levels are extremely reduced in CDSP.

[4] Newborn screening for CACT deficiency can be performed through blood tests, which measure the levels of carnitine and acylcarnitines in newborns.

[5] Blood acylcarnitine analysis shows a very high acyl fraction with marked increase in C16, C18, and C18:1 species. Free carnitine is very low.

[6] Newborn screening for CACT deficiency can be performed through blood tests, which measure the levels of carnitine and acylcarnitines in newborns.

[7] Blood Tests can help detect low levels of carnitine and high levels of acylcarnitines in the blood, which are characteristic of CACT deficiency.

[8] Genetic testing can confirm a diagnosis of CACT deficiency by identifying mutations in the SLC25A20 gene, which codes for the CACT protein.

[9] A skin biopsy may be performed to demonstrate reduced carnitine transport in fibroblasts, confirming a diagnosis of primary carnitine deficiency, including CACT deficiency.

[10] Acylcarnitine analysis may be performed as a dedicated standalone diagnostic test, or as a component of a multiplexed method for newborn screening that includes analysis of other analytes such as free carnitine and acyl-CoA dehydrogenase activity.

Differential Diagnosis of CACT Deficiency

Carnitine-acylcarnitine translocase (CACT) deficiency is a condition that can be challenging to diagnose due to its non-specific symptoms. However, there are several conditions that need to be ruled out in the differential diagnosis of CACT deficiency.

Conditions to Consider:

• Carnitine Palmitoyl Transferase II Deficiency: This condition is often misinterpreted as CACT deficiency, and it's essential to fully exclude this possibility before making a diagnosis (9).
• Other Fatty Acid Oxidation Disorders: Conditions like medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency, and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency can present with similar symptoms to CACT deficiency.
• Other Metabolic Disorders: Conditions like mitochondrial trifunctional protein (MTP) deficiency, HMG-CoA lyase deficiency, and pyruvate carboxylase deficiency can also be considered in the differential diagnosis.

Key Diagnostic Features:

• Clinical Signs: Early signs that may suggest CACT deficiency include non-specific dicarboxylic aciduria, blood acylcarnitine analysis showing a very high acyl fraction with marked abnormalities (3), and neurological involvement, seizures, and developmental delay (4).
• Genetic Testing: Mutations in the SLC25A20 gene cause CACT deficiency, and genetic testing can confirm this diagnosis (7).

References:

• [1] - The diagnosis of CACT deficiency is established in a proband by identification of biallelic pathogenic (or likely pathogenic) variants in SLC25A20.
• [3] - Blood acylcarnitine analysis shows a very high acyl fraction with marked abnormalities.
• [4] - Neurological involvement, seizures, and developmental delay are also present.
• [7] - Mutations in the SLC25A20 gene cause CACT deficiency.
• [9] - Diagnosis of CACT deficiency can sometimes be misinterpreted as carnitine palmitoyl transferase II deficiency.