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
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...
Published in: | International Journal of Neonatal Screening |
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ftpubmed:oai:pubmedcentral.nih.gov:5523953 2023-05-15T15:07:40+02:00 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 Dowsett, Leah Lulis, Lauren Ficicioglu, Can Cuddapah, Sanmati 2017-04-28 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5523953/ https://doi.org/10.3390/ijns3020010 en eng http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5523953/ http://dx.doi.org/10.3390/ijns3020010 http://creativecommons.org/licenses/by/4.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). CC-BY Article Text 2017 ftpubmed https://doi.org/10.3390/ijns3020010 2017-07-30T00:13:21Z 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. Text Arctic inuit PubMed Central (PMC) Arctic International Journal of Neonatal Screening 3 2 10 |
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Article Dowsett, Leah Lulis, Lauren Ficicioglu, Can Cuddapah, Sanmati 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 |
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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. |
format |
Text |
author |
Dowsett, Leah Lulis, Lauren Ficicioglu, Can Cuddapah, Sanmati |
author_facet |
Dowsett, Leah Lulis, Lauren Ficicioglu, Can Cuddapah, Sanmati |
author_sort |
Dowsett, Leah |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publishDate |
2017 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5523953/ https://doi.org/10.3390/ijns3020010 |
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Arctic |
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Arctic |
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Arctic inuit |
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Arctic inuit |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5523953/ http://dx.doi.org/10.3390/ijns3020010 |
op_rights |
http://creativecommons.org/licenses/by/4.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.3390/ijns3020010 |
container_title |
International Journal of Neonatal Screening |
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3 |
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2 |
container_start_page |
10 |
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1766339127299538944 |