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 |
---|---|
Main Authors: | , , , |
Format: | Text |
Language: | English |
Published: |
Multidisciplinary Digital Publishing Institute
2017
|
Subjects: | |
Online Access: | https://doi.org/10.3390/ijns3020010 |
id |
ftmdpi:oai:mdpi.com:/2409-515X/3/2/10/ |
---|---|
record_format |
openpolar |
spelling |
ftmdpi:oai:mdpi.com:/2409-515X/3/2/10/ 2023-08-20T04:04:42+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 Leah Dowsett Lauren Lulis Can Ficicioglu Sanmati Cuddapah 2017-04-28 application/pdf https://doi.org/10.3390/ijns3020010 EN eng Multidisciplinary Digital Publishing Institute https://dx.doi.org/10.3390/ijns3020010 https://creativecommons.org/licenses/by/4.0/ International Journal of Neonatal Screening; Volume 3; Issue 2; Pages: 10 carnitine palmitoyltransferase deficiency CPT1A fatty acid oxidation disorders elevated liver transaminases Ashkenazi Jewish neonatal screening Text 2017 ftmdpi https://doi.org/10.3390/ijns3020010 2023-07-31T21:06:22Z 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 MDPI Open Access Publishing Arctic International Journal of Neonatal Screening 3 2 10 |
institution |
Open Polar |
collection |
MDPI Open Access Publishing |
op_collection_id |
ftmdpi |
language |
English |
topic |
carnitine palmitoyltransferase deficiency CPT1A fatty acid oxidation disorders elevated liver transaminases Ashkenazi Jewish neonatal screening |
spellingShingle |
carnitine palmitoyltransferase deficiency CPT1A fatty acid oxidation disorders elevated liver transaminases Ashkenazi Jewish neonatal screening Leah Dowsett Lauren Lulis Can Ficicioglu Sanmati Cuddapah 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 |
topic_facet |
carnitine palmitoyltransferase deficiency CPT1A fatty acid oxidation disorders elevated liver transaminases Ashkenazi Jewish neonatal screening |
description |
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 |
Leah Dowsett Lauren Lulis Can Ficicioglu Sanmati Cuddapah |
author_facet |
Leah Dowsett Lauren Lulis Can Ficicioglu Sanmati Cuddapah |
author_sort |
Leah Dowsett |
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 |
publisher |
Multidisciplinary Digital Publishing Institute |
publishDate |
2017 |
url |
https://doi.org/10.3390/ijns3020010 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic inuit |
genre_facet |
Arctic inuit |
op_source |
International Journal of Neonatal Screening; Volume 3; Issue 2; Pages: 10 |
op_relation |
https://dx.doi.org/10.3390/ijns3020010 |
op_rights |
https://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.3390/ijns3020010 |
container_title |
International Journal of Neonatal Screening |
container_volume |
3 |
container_issue |
2 |
container_start_page |
10 |
_version_ |
1774715082983342080 |