Fatty acid metabolism disorder not found on prenatal testing

Abstract

Case Description: A 26 year old G3P2001 presented for amniocentesis due to a family history of carnitine palmitoyltransferase 2 (CPTII) deficiency. Her first child developed seizures and passed away soon after birth; CPTII deficiency was diagnosed on the newborn screen. Both parents were confirmed to be carriers. For her second pregnancy, she opted against invasive testing. The newborn was treated proactively. Testing confirmed the child was not affected, and treatment was halted. In the current pregnancy, she opted for amniocentesis, which revealed an affected male.

Background: CPT II deficiency is a rare autosomal recessive disease caused by a mutation in a gene encoding carnitine palmitoyltransferase 2, an essential enzyme in fatty acid oxidation. Affected patients are at risk for hypoketotic hypoglycemia, seizures, hepatomegaly, cardiomyopathy, arrhythmias, and other downstream issues. A postnatal diagnosis via the newborn screen does not confer the benefit of advanced awareness of the disease and allow for preemptive treatment. CPT II deficiency can be confirmed prenatally with diagnostic testing. Amniocentesis is an invasive test associated with a low but present risk of pregnancy loss, so some may opt against the test.

Conclusion: Carriers of CPT II mutations are counseled that future pregnancies confer a 25% risk of having an affected child. Prenatal diagnostic testing is recommended for prenatal diagnosis, which allows for planning of immediate treatment in the NICU. However, opting to forgo invasive testing and preemptively treat potentially affected child until newborn screening results return, as occurred in this patient’s second pregnancy, is also an option.

Clinical Significance: CPT II deficiency is a rare disease that can have devastating effects in newborns without a known diagnosis. Parents with known carrier status must be extensively counseled on their options regarding prenatal and postnatal screening as well as immediate newborn care.