SNP Shot: Genomic Insights

Carnitine palmitoyltransferase II (CPT II) deficiency is a metabolic disorder that impairs the body's ability to utilize certain fats for energy, especially during periods of fasting. This deficiency has three primary forms: a lethal neonatal form, a severe infantile hepatocardiomuscular form, and a myopathic form.

The lethal neonatal form of CPT II deficiency manifests shortly after birth. Affected infants experience respiratory failure, seizures, liver failure, cardiomyopathy (weakened heart muscle), and arrhythmia (irregular heartbeat). They also exhibit hypoketotic hypoglycemia, a condition characterized by low blood glucose and a low level of ketones (energy-producing compounds derived from fat breakdown). Brain and kidney abnormalities are also common. Infants with this form typically survive only a few days to months.

The severe infantile hepatocardiomuscular form of CPT II deficiency affects the liver, heart, and muscles. Symptoms usually emerge within the first year of life and include recurring episodes of hypoketotic hypoglycemia, seizures, hepatomegaly (enlarged liver), cardiomyopathy, and arrhythmia. These problems are often triggered by fasting or illnesses like viral infections. Individuals with this form are susceptible to liver failure, nervous system damage, coma, and sudden death.

The myopathic form represents the mildest form of CPT II deficiency. Its defining feature is recurrent episodes of myalgia (muscle pain) and weakness, accompanied by rhabdomyolysis (muscle tissue breakdown). Rhabdomyolysis releases myoglobin, a protein that the kidneys process and excrete in the urine (myoglobinuria). Myoglobinuria causes the urine to appear red or brown and can potentially damage the kidneys, leading to life-threatening kidney failure. Triggers for myalgia and rhabdomyolysis episodes include exercise, stress, extreme temperatures, infections, or fasting. The initial episode typically occurs in childhood or adolescence. Between episodes, most individuals with the myopathic form of CPT II deficiency are asymptomatic.

Inheritance:

CPT II deficiency follows an autosomal recessive inheritance pattern. This means that both copies of the CPT II gene in each cell must have mutations for the condition to develop. Individuals with the condition inherit one mutated gene copy from each parent, who are carriers but usually do not exhibit symptoms of the deficiency.