Genotype–phenotype correlations in CPT1A deficiency detected by newborn screening in Pacific populations
Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a long chain fatty acid oxidation disorder, typically presenting with hypoketotic hypoglycaemia and liver dysfunction during fasting and intercurrent illness. Classical CPT1A deficiency is a rare disease, although a milder ‘Arctic variant'...
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ftpubmed:oai:pubmedcentral.nih.gov:9259392 2023-05-15T15:11:04+02:00 Genotype–phenotype correlations in CPT1A deficiency detected by newborn screening in Pacific populations Bernhardt, Isaac Glamuzina, Emma Dowsett, Leah K. Webster, Dianne Knoll, Detlef Carpenter, Kevin Bennett, Michael J. Maeda, Michelle Wilson, Callum 2022-03-26 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259392/ http://www.ncbi.nlm.nih.gov/pubmed/35822099 https://doi.org/10.1002/jmd2.12271 en eng John Wiley & Sons, Inc. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259392/ http://www.ncbi.nlm.nih.gov/pubmed/35822099 http://dx.doi.org/10.1002/jmd2.12271 © 2022 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. CC-BY JIMD Rep Research Reports Text 2022 ftpubmed https://doi.org/10.1002/jmd2.12271 2022-07-31T00:58:24Z Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a long chain fatty acid oxidation disorder, typically presenting with hypoketotic hypoglycaemia and liver dysfunction during fasting and intercurrent illness. Classical CPT1A deficiency is a rare disease, although a milder ‘Arctic variant' (p.P479L) is common in the Inuit population. Since the introduction of expanded metabolic screening (EMS), the newborn screening programmes of Hawai'i and New Zealand (NZ) have detected a significant increase in the incidence of CPT1A deficiency. We report 22 individuals of Micronesian descent (12 in NZ and 10 in Hawai'i), homozygous for a CPT1A c.100T>C (p.S34P) variant detected by EMS or ascertained following diagnosis of a family member. No individuals with the Micronesian variant presented clinically with metabolic decompensation prior to diagnosis or during follow‐up. Three asymptomatic homozygous adults were detected following the diagnosis of their children by EMS. CPT1A activity in cultured skin fibroblasts showed residual enzyme activity of 26% of normal controls. Secondly, we report three individuals from two unrelated Niuean families who presented clinically with symptoms of classic CPT1A deficiency, prior to the introduction of EMS. All were found to be homozygous for a CPT1A c.2122A>C (p.S708R) variant. CPT1A activity in fibroblasts of all three individuals was severely reduced at 4% of normal controls. Migration pressure, in part due to climate change may lead to increased frequency of presentation of Pacific peoples to regional metabolic services around the world. Knowledge of genotype–phenotype correlations in these populations will therefore inform counselling and treatment of those detected by newborn screening. Text Arctic Climate change inuit PubMed Central (PMC) Arctic New Zealand Pacific JIMD Reports 63 4 322 329 |
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Research Reports Bernhardt, Isaac Glamuzina, Emma Dowsett, Leah K. Webster, Dianne Knoll, Detlef Carpenter, Kevin Bennett, Michael J. Maeda, Michelle Wilson, Callum Genotype–phenotype correlations in CPT1A deficiency detected by newborn screening in Pacific populations |
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Research Reports |
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Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a long chain fatty acid oxidation disorder, typically presenting with hypoketotic hypoglycaemia and liver dysfunction during fasting and intercurrent illness. Classical CPT1A deficiency is a rare disease, although a milder ‘Arctic variant' (p.P479L) is common in the Inuit population. Since the introduction of expanded metabolic screening (EMS), the newborn screening programmes of Hawai'i and New Zealand (NZ) have detected a significant increase in the incidence of CPT1A deficiency. We report 22 individuals of Micronesian descent (12 in NZ and 10 in Hawai'i), homozygous for a CPT1A c.100T>C (p.S34P) variant detected by EMS or ascertained following diagnosis of a family member. No individuals with the Micronesian variant presented clinically with metabolic decompensation prior to diagnosis or during follow‐up. Three asymptomatic homozygous adults were detected following the diagnosis of their children by EMS. CPT1A activity in cultured skin fibroblasts showed residual enzyme activity of 26% of normal controls. Secondly, we report three individuals from two unrelated Niuean families who presented clinically with symptoms of classic CPT1A deficiency, prior to the introduction of EMS. All were found to be homozygous for a CPT1A c.2122A>C (p.S708R) variant. CPT1A activity in fibroblasts of all three individuals was severely reduced at 4% of normal controls. Migration pressure, in part due to climate change may lead to increased frequency of presentation of Pacific peoples to regional metabolic services around the world. Knowledge of genotype–phenotype correlations in these populations will therefore inform counselling and treatment of those detected by newborn screening. |
format |
Text |
author |
Bernhardt, Isaac Glamuzina, Emma Dowsett, Leah K. Webster, Dianne Knoll, Detlef Carpenter, Kevin Bennett, Michael J. Maeda, Michelle Wilson, Callum |
author_facet |
Bernhardt, Isaac Glamuzina, Emma Dowsett, Leah K. Webster, Dianne Knoll, Detlef Carpenter, Kevin Bennett, Michael J. Maeda, Michelle Wilson, Callum |
author_sort |
Bernhardt, Isaac |
title |
Genotype–phenotype correlations in CPT1A deficiency detected by newborn screening in Pacific populations |
title_short |
Genotype–phenotype correlations in CPT1A deficiency detected by newborn screening in Pacific populations |
title_full |
Genotype–phenotype correlations in CPT1A deficiency detected by newborn screening in Pacific populations |
title_fullStr |
Genotype–phenotype correlations in CPT1A deficiency detected by newborn screening in Pacific populations |
title_full_unstemmed |
Genotype–phenotype correlations in CPT1A deficiency detected by newborn screening in Pacific populations |
title_sort |
genotype–phenotype correlations in cpt1a deficiency detected by newborn screening in pacific populations |
publisher |
John Wiley & Sons, Inc. |
publishDate |
2022 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259392/ http://www.ncbi.nlm.nih.gov/pubmed/35822099 https://doi.org/10.1002/jmd2.12271 |
geographic |
Arctic New Zealand Pacific |
geographic_facet |
Arctic New Zealand Pacific |
genre |
Arctic Climate change inuit |
genre_facet |
Arctic Climate change inuit |
op_source |
JIMD Rep |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259392/ http://www.ncbi.nlm.nih.gov/pubmed/35822099 http://dx.doi.org/10.1002/jmd2.12271 |
op_rights |
© 2022 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
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CC-BY |
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https://doi.org/10.1002/jmd2.12271 |
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JIMD Reports |
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63 |
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4 |
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322 |
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329 |
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