Utility of Genetic Testing for Confirmation of Abnormal Newborn Screening in Disorders of Long-Chain Fatty Acids: A Missed Case of Carnitine Palmitoyltransferase 1A (CPT1A) Deficiency.

Leah Dowsett,Sanmati Cuddapah,Can Ficicioglu,Lauren Lulis

doi:10.3390/ijns3020010

Abstract

An 18-month-old male was evaluated after presenting with disproportionately elevated liver transaminases in the setting of acute gastroenteritis. He had marked hepatomegaly on physical exam that was later confirmed with an abdominal ultrasound. Given this clinical picture, suspicion for a fatty acid oxidation disorder was raised. Further investigation revealed that his initial newborn screen was positive for carnitine palmitoyltransferase 1A (CPT1A) deficiency—a rare autosomal recessive disorder of long-chain fatty acid oxidation. Confirmatory biochemical testing in the newborn period showed carnitine levels to be unexpectedly low with a normal acylcarnitine profile. Thus, it was considered to be a false-positive newborn screen and metabolic follow-up was not recommended. Repeat biochemical testing during this hospitalization revealed a normal acylcarnitine profile. The only abnormalities noted were a low proportion of acylcarnitine species from plasma, an elevated free-to-total carnitine ratio, and mild hypoketotic medium chain dicarboxylic aciduria on urine organic acids. Gene sequencing of CPT1A revealed a novel homozygous splice site variant that confirmed his diagnosis. CPT1A deficiency has a population founder effect in the Inuit and other Arctic groups, but has not been previously reported in persons of Ashkenazi Jewish ancestry.

Highlights

Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a rare autosomal recessive disorder of long-chain fatty acid oxidation
As previously reported by Wanders et al, normal acylcarnitine profiles do not rule out CPT1A deficiency and mild fatty acid oxidation defects [11]
Repeat newborn screening from a dried blood spot is a necessary step in patients with an initial positive screen for CPT1A deficiency

Summary

Introduction

Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a rare autosomal recessive disorder of long-chain fatty acid oxidation. Lab abnormalities seen during such a crisis includes hypoglycemia, hyperammonemia, low acylcarnitines, elevated levels of total and/or free carnitine, transaminitis, and elevated coagulation studies. We describe a patient who had normal biochemical profiles in the newborn period who was subsequently diagnosed with CPT1A deficiency only after molecular testing revealed him to be homozygous for a splice-site variant in this gene. This condition, which has a population founder effect in the Inuit and other arctic groups, has not been previously reported in persons of Ashkenazi Jewish ancestry [2,3,4]

Case Report

Findings

Discussion

Conclusions