Clinical Guidance

A consistent genotype-phenotype correlation is found between CPT2 missense pathogenic variants (including the common ) and the myopathic form; these are referred to as pathogenic variants that cause "mild" form of the disease. CPT2 pathogenic null variants leading either to truncation of the protein or to mRNA degradation are referred to as pathogenic variants associated with the lethal neonatal form. However, several pathogenic variants are associated with both the mild and severe forms of CPT II deficiency, suggesting a role for other unknown modulators (intragenic variants; epigenetic or environmental factors) . For a list of variants and their predicted phenotype, see , , and . Lethal neonatal form.

Source: GeneReviews — "Carnitine Palmitoyltransferase II Deficiency"

Diagnostic Criteria

Suggestive Findings

Carnitine palmitoyltransferase II (CPT II) deficiency should be suspected in individuals with the following clinical features (by age) and supportive laboratory findings.

Clinical features (by age)

Source: GeneReviews — "Carnitine Palmitoyltransferase II Deficiency"

Differential Diagnosis

Elevated acylcarnitines. The differential diagnosis of an elevation of C12 to C18 acylcarnitines, notably of C16 and C18:1, includes glutaric acidemia type II (see Multiple Acyl-CoA Dehydrogenase Deficiency) and carnitine-acylcarnitine translocase deficiency, which can be excluded by additional screening of urinary metabolites such as glutaric and 3-OH-glutaric acid.

Neonatal Form

Carnitine-acylcarnitine translocase (CACT) deficiency. The neonatal phenotype of CACT deficiency, one of the most severe and usually lethal mitochondrial fatty-acid oxidation abnormalities, is characterized by hypoketotic hypoglycemia, hyperammonemia, cardiac abnormalities, and early death.

Source: GeneReviews — "Carnitine Palmitoyltransferase II Deficiency"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with carnitine palmitoyltransferase II (CPT II) deficiency, the following are recommended:

• Neurologic examination

• Strength testing

• Review of dietary association of symptoms

• Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Current treatment for long-chain fatty-acid oxidation disorders:

• Avoid known triggers.

• Reduce the amount of long-chain dietary fat while covering the need for essential fatty acids.

• Provide carnitine to convert potentially toxic long-chain acyl-CoAs to acylcarnitines.

• Provide a large fraction of calories as carbohydrates to reduce body fat utilization and prevent hypoglycemia.

• Provide approximately one third of the calories as even-chain medium chain triglycerides (MCT). Metabolism of the eight to ten carbon fatty acids in MCT oil, for example, is independent of CPT I, carnitine-acylcarnitine translocase, CPT II, very long-chain acyl-CoA dehydrogenase (VLCAD), trifunctional protein, and long-chain hydroxy-acyl-CoA dehydrogenase deficiency (LCHAD) enzyme activities.

Prevention of Primary Manifestations

Appropriate measures include the following:

• Infusions of glucose during intercurrent infections to prevent catabolism

Note: Oral glucose cannot achieve this effect.

Source: GeneReviews — "Carnitine Palmitoyltransferase II Deficiency"

Clinical Guidance

Extended fasting and prolonged exercise are to be avoided. Reports of medication-induced side effects in individuals with CPT II deficiency are rare. Relying mostly on case reports, the following agents should be avoided:

• Valproic acid

• General anesthesia

• Ibuprofen

• Diazepam in high doses

Source: GeneReviews — "Carnitine Palmitoyltransferase II Deficiency"

Therapies Under Investigation

Promising results have been obtained with treatment of cardiomyopathy and rhabdomyolysis in long-chain fat oxidation disorders using anaplerotic odd-chain triglycerides . These results were confirmed in seven individuals with CPT II deficiency, who avoided rhabdomyolysis or hospitalization while on the triheptanoin (anaplerotic) diet. Affected individuals returned to normal physical activity including strenuous sports . Fibrates are a class of hypolipidemic drugs that increase high-density lipoprotein levels by mRNA upregulation of many lipid-metabolism genes through interaction with the steroid/thyroid transcription factor PPARa.

Source: GeneReviews — "Carnitine Palmitoyltransferase II Deficiency"

Surveillance Guidelines

Annual or more frequent monitoring to regulate medication and diet is indicated.

Source: GeneReviews — "Carnitine Palmitoyltransferase II Deficiency"