Carnitine palmitoyltransferase deficiency - A difficult disorder for newborn screening

Abstract

Introduction: Carnitine palmitoyltransferase II (CPT II) deficiency is a long-chain fatty-acid oxidation disorder with different clinical presentations: lethal neonatal form, severe infantile hepato-cardio-mus-cular form, and later onset rhabdomyolysis or myopathy. Case report: A female infant identified through newborn screening was reviewed at 3 weeks of age, indicating normal growth and development on breast feeds. A feeding plan including breast milk and formula high in medium chain triglycerides (MCT) was commenced. Subsequent biochemical studies including plasma acylcar-nitine analysis, urine organic acids, and cultured fibroblast acylcarnitine analyses were done. CPT II enzyme studies on blood (3% of controls) and fibroblasts (5% of controls) confirmed this diagnosis. At three months of age, after a short history of MCT feed refusal and a respiratory infection, she presented with hypoglycemia, initially responsive to glucose infusion. She subsequently had an unresponsive episode with hypothermia, mild acidosis and ammonia elevation. She responded to beta-hydroxybutyrate (ketones) and hyper-hydration with dextrose-saline. Her serum ammonia levels improved, from 304 to 38 umol/L, (ref range: 10-50 umol/L) and she had normal neurology and brain MRI after recovery. Whole exome sequencing showed a likely pathogenic c.136C>T p.(Gln46∗) variant and one VOUS c.371G>C p.Arg124Pro in the CPT2 gene (phase unknown). Genetic counseling was recommended for future family planning. At her most recent visit aged 6 months, development appeared normal with some concern about swallow functions. Conclusion: It can be difficult to determine from newborn screening results when and how individuals with CPT II may present and what their optimal treatment might be.L6298897502019-11-25 <br />