Carnitine palmitoyltransferase II deficiency

Overview

Carnitine palmitoyl transferase II deficiency (CPT-II) is a metabolic disorder characterized by an enzymatic defect that prevents long-chain fatty acids from being transported into the mitochondria for utilization as an energy source. There are two main subtypes of the disorder with each involving a slightly different form of the enzyme. Type II has three subtypes: the myopathic form affects mainly the muscles; the hepatocardiomuscular form affects the liver and heart muscle; and the lethal neonatal form affects muscles and organs and usually results in death during the first year of life.

Symptoms

The list of signs and symptoms mentioned in various sources for Carnitine palmitoyl transferase II deficiency includes the 44 symptoms listed below:

  • Aching muscles - type II myopathic form
  • Fatigue - type II myopathic form
  • Breakdown of muscle tissue - type II myopathic form
  • Myoglobins in the urine after cold exposure - type II myopathic form
  • Myoglobins in the urine after fever - type II myopathic form
  • Myoglobins in the urine after caloric deprivation - type II myopathic form
  • Myoglobins in the urine after vomiting- type II myopathic form
  • Muscle stiffness - type II myopathic form
  • Muscle weakness - type II myopathic form
  • Muscle pain - type II myopathic form
  • Breakdown of muscle tissue - type II myopathic form
  • Dark reddish-brown urine - type II myopathic form
  • Aching muscles - type II hepatocardiomuscular form
  • Fatigue - type II hepatocardiomuscular form
  • Myoglobins in the urine after cold exposure - type II hepatocardiomuscular form
  • Myoglobins in the urine after fever - type II hepatocardiomuscular form
  • Myoglobins in the urine after caloric deprivation - type II hepatocardiomuscular form
  • Myoglobins in the urine after vomiting - type II hepatocardiomuscular form
  • Muscle stiffness - type II hepatocardiomuscular form
  • Muscle weakness - type II hepatocardiomuscular form
  • Breakdown of muscle tissue - type II hepatocardiomuscular form
  • Dark reddish-brown urine - type II hepatocardiomuscular form
  • Liver symptoms - type II hepatocardiomuscular form
  • Heart symptoms - type II hepatocardiomuscular form
  • Periodic low ketone level - type II hepatocardiomuscular form
  • Low blood sugar - type II hepatocardiomuscular form
  • Loss of consciousness - type II hepatocardiomuscular form
  • Seizures - type II hepatocardiomuscular form
  • Enlarged liver - type II hepatocardiomuscular form
  • Heart symptoms - type II hepatocardiomuscular form
  • Aching muscles - type II lethal neonatal form
  • Fatigue - type II lethal neonatal form
  • Myoglobins in the urine after cold exposure - type II lethal neonatal form
  • Myoglobins in the urine after fever - type II lethal neonatal form
  • Myoglobins in the urine after caloric deprivation - type II lethal neonatal form
  • Myoglobins in the urine after vomiting - type II lethal neonatal form
  • Muscle stiffness - type II lethal neonatal form
  • Muscle weakness - type II lethal neonatal form
  • Breakdown of muscle tissue - type II lethal neonatal form
  • Dark reddish-brown urine - type II lethal neonatal form
  • Seizures - type II lethal neonatal form
  • Irregular heart beat - type II lethal neonatal form
  • Brain abnormalities - type II lethal neonatal form
  • Kidney abnormalities - type II lethal neonatal form

Causes

CPT II deficiency occurs when an enzyme, called “carnitine palmitoyltransferase II” (CPT II) is either missing or not working properly. This enzyme’s job is to help change certain fats in the food we eat into energy. It also helps break down fat already stored in the body.

Energy from fat keeps us going whenever our bodies run low of their main source of energy, a type of sugar called glucose . Our bodies rely on fat when we don’t eat for a stretch of time - like when we miss a meal or when we sleep.

When the CPT II enzyme is missing or not working, the body cannot use fat for energy, and must rely solely on glucose. Although glucose is a good source of energy, there is a limited amount available. Once the glucose has been used up, the body tries to use fat without success. This leads to low blood sugar, called hypoglycemia, and to the build up of harmful substances in the blood.

Source: MDH

Prevention

CPT II deficiency is inherited in an autosomal recessive manner. It affects both boys and girls equally.

Everyone has a pair of genes that make the CPT II enzyme. In children with CPT II deficiency, neither of these genes works correctly. These children inherit one non-working gene for the condition from each parent.

Parents of children with CPT II deficiency rarely have the disorder. Instead, each parent has a single non-working gene for CPT II deficiency. They are called carriers. Carriers do not have the condition because the other gene of this pair is working correctly.

When both parents are carriers, there is a 25% chance in each pregnancy for the child to have CPT II deficiency. There is a 50% chance for the child to be a carrier, just like the parents. And, there is a 25% chance for the child to have two working genes.

Genetic counseling is available to families who have children with CPT II deficiency. Genetic counselors can answer your questions about how the condition is inherited, choices during future pregnancies, and how to test other family members. Ask your doctor about a referral to a genetic counselor.

Souece: MDH

Diagnosis

Genetic testing for CPT II deficiency can be done on a blood sample. Genetic testing, also called DNA testing, looks for changes in the pair of genes that cause the condition. In some children, both gene changes can be found. However, in other children, neither or only one of the two gene changes can be found, even though we know they are present. 

DNA testing is not necessary to diagnose your child. It can be helpful for carrier testing or prenatal diagnosis, discussed below.

CPT II deficiency can be confirmed by a special enzyme test on a skin sample.

Diagnostic testing

Brothers and sisters of an affected child can be tested for CPT-II deficiency using either a DNA test or a special enzyme test. 

Carrier testing

If both gene changes have been found in the child with CPT-II deficiency, other family members can have DNA testing to see if they are carriers.

If DNA testing would not be helpful, other methods of carrier testing may be available. Your metabolic doctor or genetic counselor can answer your questions about carrier testing.

Prognosis

Prognosis of Carnitine palmitoyl transferase 2 deficiency: death usually in first year of life - type II lethal neonatal form

Treatment

Certain treatments may be advised for some children but not others. When necessary, treatment is usually needed throughout life. The following are treatments sometimes recommended for children with this condition:

1. Avoid going a long time without food

Infants and young children with CPT II deficiency need to eat frequently to prevent a metabolic crisis. Your metabolic doctor will tell you how often your child needs to be fed. In general, it is often suggested that infants be fed every four to six hours. Some babies need to eat even more frequently than this. It is important that infants be fed during the night. They may need to be woken up to eat if they do not wake up on their own. Your metabolic doctor and dietician will give you an appropriate feeding plan for your infant. Your doctor will also give you a ‘sick day’ plan tailored to your child’s needs for you to follow during illnesses or other times when your child will not eat.

Your metabolic doctor will continue to advise you on how often your child should eat as he or she gets older. When they are well, many teens and adults with CPT II deficiency can go without food for up to 12 hours without problems. The other treatments usually need to be continued throughout life.

2. Diet

Sometimes a low fat, high carbohydrate food plan is recommended. Carbohydrates give the body many types of sugar that can be used as energy. In fact, for children needing this treatment, most food in the diet should be carbohydrates (bread, pasta, fruit, vegetables, etc.) and protein (lean meat and low-fat dairy foods). Any diet changes should be made under the guidance of an experienced dietician. Children with CPT II deficiency cannot use certain building blocks of fat called "long chain fatty acids". Your dietician can help create a food plan low in these fats. Much of the rest of the fat in the diet will likely be in the form of medium chain fatty acids.

Ask your doctor whether your child needs to have any changes in his or her diet.

3. MCT oil and L-carnitine

Medium Chain Triglyceride oil (MCT oil) is often used as part of the food plan for people with CPT II deficiency. This special oil has medium chain fatty acids that can be used in small amounts for energy. Your metabolic doctor or dietician can guide you in how to use this supplement.

Some children and adults may be helped by taking L-carnitine. This is a safe and natural substance that helps body cells make energy. It also helps the body get rid of harmful wastes. Your doctor will decide whether or not your child needs L-carnitine. Unless you are advised otherwise, use only L-carnitine prescribed by your doctor. Do not use any supplements without checking with your doctor.

4. Call your doctor at the start of any illness:

Always call your health care provider right away when your child has any of the following:

• poor appetite

• low energy or excessive sleepiness

• vomiting

• diarrhea

• an infection

• a fever

• persistent muscle pain, weakness, or reddish-brown color to the urine

Babies and children with CPT II deficiency need to eat extra starchy food and drink more fluids during any illness - even if they may not feel hungry – or they could have a metabolic crisis. Children who are sick often don’t want to eat. If they won’t or can’t eat, they may need to be treated in the hospital to prevent a metabolic crisis. Ask your metabolic doctor if you should carry a special travel letter with medical instructions for your child’s care.

5. Avoid long periods of exercise and avoid getting cold

Long periods of strenuous exercise can trigger symptoms in both children and adults. So can cold weather. Muscle effects can include:

• muscle aches

• cramps

• weakness

• reddish-brown urine

If muscle symptoms occur, prompt treatment is needed to prevent kidney damage. Children or adults with muscle symptoms should:

• drink fluids right away

• eat something starchy or sugary

• get to a hospital for treatment

To help prevent muscle symptoms:

• avoid prolonged or heavy exercise

• keep the body warm

• eat starchy or sugary food before and during periods of moderate exercise

 

Resources

Fatty Oxidation Disorders (FOD) Family Support Group