Clinical Guidance

CPT1A pathogenic variant , observed in the Inuit population of the Arctic and sub-Arctic, is associated with a partial loss of CPT1 function but does not appear to cause acute hepatic failure . In fact, most children homozygous for this variant never develop any manifestations of CPT1A deficiency. However, evidence suggests that infants who are homozygous for p.Pro479Leu have impaired fasting tolerance and increased risk of infant mortality . Many individuals with this variant may be missed by NBS with acylcarnitine profile alone, so Alaskan NBS programs incorporate sequencing for this variant (see health.alaska.gov). In a study using whole-genome high-coverage sequence data of Arctic populations, p.

Source: GeneReviews — "Carnitine Palmitoyltransferase 1A Deficiency"

Diagnostic Criteria

No consensus clinical diagnostic criteria for carnitine palmitoyltransferase 1A (CPT1A) deficiency have been published.

Suggestive Findings

Source: GeneReviews — "Carnitine Palmitoyltransferase 1A Deficiency"

Differential Diagnosis

A number of other fetal fatty acid oxidation defects are associated with a similar risk to the heterozygous mother of developing acute fatty liver of pregnancy, typically in the third trimester, prompting further investigation of the newborn for a fatty acid oxidation defect. The absence (or paucity) of ketone bodies during a period of hypoglycemia should increase suspicion for one of the disorders of fatty acid oxidation or the carnitine cycle, including carnitine palmitoyltransferase 1A (CPT1A) deficiency. Selected genes of interest in the differential diagnosis of CPT1A deficiency are listed in . Table 2. Selected Genes of Interest in the Differential Diagnosis of Carnitine Palmitoyltransferase 1A Deficiency

Management Guidelines

No clinical practice guidelines for carnitine palmitoyltransferase 1A (CPT1A) deficiency have been published. In the absence of published consensus guidelines, the following recommendations are based on available evidence and literature on the subject. When CPT1A deficiency is suspected during the diagnostic evaluation (for example, because of a suggestive carnitine and acylcarnitine profile; see ), metabolic treatment including fasting precautions should be initiated immediately. Development and evaluation of treatment plans, training and education of affected individuals and their families, and avoidance of side effects of dietary treatment (e.g., malnutrition, growth failure) require a multidisciplinary approach including multiple subspecialists, with oversight and expertise from a specialized metabolic center. Guidelines and current management strategies for the treatment of CPT1A deficiency and other long-chain fatty acid oxidation disorders can be found at www.newbornscreening.info and (full text). The British Inherited Metabolic Disease Group (BIMDG) website has a specific emergency management protocol for CPT1A deficiency (see Emergency Guides - BIMDG).

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with CPT1A deficiency, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 3.

Source: GeneReviews — "Carnitine Palmitoyltransferase 1A Deficiency"

Clinical Guidance

Avoid fasting, including during periods of preparation and recovery from planned surgery or sedation (see CPT I Deficiency — New England Consortium of Metabolic Programs). During periods of fasting, long-chain fatty acids are typically broken down into ketones and provide an important energy source for the liver and other tissues. Due to the metabolic block caused by this disorder, ketone production is limited, and fasting can trigger hypoketotic hypoglycemia. Potentially hepatotoxic agents such as valproate and salicylate should be used with caution if there is evidence of hepatic dysfunction . Adverse effects of pharmacologic agents have not been reported in individuals with CPT1A deficiency. Avoid viral or bacterial infections. Avoid overfeeding in individuals without acute illness to reduce long-term risk of obesity.

Source: GeneReviews — "Carnitine Palmitoyltransferase 1A Deficiency"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Carnitine Palmitoyltransferase 1A Deficiency"

Surveillance Guidelines

Table 7. Carnitine Palmitoyltransferase 1A Deficiency: Recommended Surveillance

Source: GeneReviews — "Carnitine Palmitoyltransferase 1A Deficiency"