A case study of lethal neonatal CPT II deficiency: Novel insights from genetic analysis.

Introduction: Carnitine Palmitoyltransferase II (CPT II) deficiency encompasses a spectrum of disorders, with the lethal neonatal form (LNF) representing the rarest and most severe. While there are numerous CPT2 gene variants that can cause CPT II deficiency, only 16 variants of these are known to be associated with LNF. This report presents the case of a neonatal male diagnosed with lethal CPT II deficiency, characterized by the presence of two heterogeneous variants. Additionally, we provide a comprehensive review of all clinical symptoms, biochemistry, and reported pathogenic variants associated with LNF CPT II deficiency.

Case presentation: A neonatal male exhibited typical symptoms and biochemical features of CPT II deficiency, along with abnormal long-chain fatty acid profiles, notably an exceptionally high level of C18OH. Genetic analysis of the dried blood spot (DBS) sample revealed two heterozygous variants: CPT2 p.E174K and p.R554X. Both the healthy father and mother carried heterozygous variants, p.R554X and p.E174K, respectively.

Discussion: The symptoms of the LNF CPT II deficiency are characterized by the unavailability of fatty acids for energy production and the accumulation of lipids in tissues, primarily due to the extremely low activity of CPT II. The genetic variants associated with these cases are notably limited, and all of them are classified as 'severe' variants. In the presented case, the co-occurrence of p.R554X with another severe variant, p.E174K, manifests as LNF, this compelling evidence strongly supports the assertion that p.R554X is a potentially severe pathogenic variant contributing to CPT II deficiency.

Conclusion: This report represents the initial documentation of a LNF CPT II deficiency case characterized by the presence of two heterozyous CPT2 variants: p.E174K and p.R554X. As a result, the p.R554X variant is potentially classified as a severe pathogenic variant. It further emphasizes the significance of early detection and precise mutation classification for effective disease.