Guidance for primary care clinicians receiving a positive newborn screen result

Other Names

ICD-10 Coding

Disorder Category

Abnormal Finding

Tested By

Carnitine palmitoyltransferase 1A (CPT1) is a mitochondrial enzyme involved in the conjugation of fatty acids to carnitine for subsequent transfer inside mitochondria through the action of a translocase. Variants in the CPT1A gene cause CPT1 deficiency. Deficient CPT1 activity results in impaired energy production, which usually manifests during prolonged fasting and/or increased energy demands (fever, stress), resulting in acute hepatic encephalopathy and hypoketotic hypoglycemic crises. CPT1A is predominantly expressed in the liver; therefore, unlike other fatty acid oxidation disorders, the muscle and heart are not primarily affected. Acute fatty liver of pregnancy may occur in a heterozygous mother of an affected fetus. Presentation in the neonatal period is rare.

Clinical Characteristics

Incidence

Inheritance

Next Steps After a Positive Screen

• Contact the family to inform them of the positive result and ask if the infant has shown signs of lethargy, poor feeding, or seizures.
• Consult with a pediatric metabolic specialist immediately.
• Evaluate the newborn for lethargy, liver disease, or seizures. If any of these signs are present or the newborn is ill, transport to a hospital for further treatment with help from the metabolic specialist.
• Initiate confirmatory/diagnostic testing and management, as recommended by the specialist (see below).

Confirming the Diagnosis

• To confirm the diagnosis of CPT1, work with Newborn Screening Services (see UT providers [3]).
• Additional testing may include glucose, blood gas, electrolytes, liver function tests, ammonia level, quantitative plasma acylcarnitine profile, enzyme activity assay in cultured fibroblasts, and CPT1A gene sequencing. The increased C0/(C16+C18) ratio is better detected from the dried blood spot collected for newborn screening. In plasma, C0 can be only mildly increased with low levels of C16 and C18.

If the Diagnosis is Confirmed

• For evaluation and ongoing collaborative management, consult Biochemical Genetics (Metabolics) (see UT providers [2]).
• Educate the family regarding signs, symptoms, and the need to avoid fasting and seek urgent care when the infant becomes ill. See CPT1 Deficiency - Information for Parents (STAR-G) for additional information.
• Provide a letter and, when old enough, a MedicAlert bracelet indicating the risk for hypoglycemia and need for urgent treatment with IV glucose when illness or stress leads to symptoms.
• Provide frequent, low-fat, and high-carbohydrate meals and snacks. In some cases, cornstarch is added to meals.
• Medium-chain triglyceride oil supplements may be indicated for some children.