Carnitine palmitoyltransferase I deficiency

autorecessive

Carnitine Palmitoyltransferase I Deficiency (CPT-I deficiency) is a rare genetic disorder that affects the body's ability to metabolize fatty acids for energy. This condition is part of a group of disorders known as fatty acid oxidation disorders. CPT-I plays a crucial role in the transport of long-chain fatty acids from the cytoplasm into the mitochondria, where they are oxidized for energy production. Deficiency in CPT-I impairs this process, leading to a buildup of fatty acids in the body and a deficiency in energy production, especially during periods of fasting or illness.

Symptoms

Symptoms of CPT-I deficiency can vary widely among affected individuals but often include episodes of low blood sugar (hypoglycemia), muscle weakness, fatigue, liver enlargement (hepatomegaly), and complications related to the heart and liver. Symptoms typically manifest in infancy or early childhood, although milder cases may not be diagnosed until later in life.

Causes

CPT-I deficiency is caused by mutations in the CPT1A gene, which provides instructions for making the enzyme carnitine palmitoyltransferase I. These genetic mutations lead to a decrease in enzyme activity, which impairs the body's ability to oxidize long-chain fatty acids.

Diagnosis

Diagnosis of CPT-I deficiency involves a combination of clinical evaluation, family history, and specialized tests. These tests may include blood tests to measure levels of carnitine and acylcarnitine, genetic testing to identify mutations in the CPT1A gene, and enzyme activity assays in fibroblasts or other tissues.

Treatment

Treatment for CPT-I deficiency focuses on managing symptoms and preventing metabolic crises. This typically involves a high-carbohydrate, low-fat diet with frequent meals to avoid fasting. In some cases, medium-chain triglycerides (MCTs) are used as an alternative energy source, as they do not require CPT-I for mitochondrial entry. Carnitine supplementation may also be recommended to enhance the removal of accumulated fatty acids.

Prognosis

The prognosis for individuals with CPT-I deficiency varies depending on the severity of the condition and the effectiveness of the management plan. With early diagnosis and appropriate treatment, many individuals can lead normal, healthy lives. However, without treatment, the condition can lead to serious complications, including liver failure, muscle damage, and potentially life-threatening metabolic crises.