Pre-symptomatically detected novel variant of CPT1A deficiency: a case report
DOI:
https://doi.org/10.18203/2349-3291.ijcp20221008Keywords:
CPT1A deficiency, Hypoketotic hypoglycemia, Fatty acid oxidation, Newborn screening, Novel mutationAbstract
CPT1A enzyme deficiency is a rare metabolic disorder of mitochondrial fatty acid oxidation, with late manifestations during infancy or childhood, including hypoketotic hypoglycemia and hepatic encephalopathy. Newborn screening in several countries include pre-symptomatic detection of CPT1A deficiency, which helps in early diagnosis and better management of the disorder. We report here a case of CPT1A deficiency, detected pre-symptomatically with newborn screening, which was confirmed by exome sequencing to be a novel c. 232G>A variant in exon 3 of CPT1A gene. This is a rare variant of uncertain significance which has not been reported in literature.
References
Carnitine palmitoyl transferase I deficiency. Genetics Home Reference. 2014. Available at http://ghr.nlm.nih.gov/condition=carnitinepalmitoyltransferaseideficiency. Accessed on 11 November 2016
Fatty acid oxidation disorders. STAR-G Screening, Technology and Research in Genetics. 2/28/2016; Available at: http://www.newbornscreening.info/ Parents/fattyaciddisorders/CPT1.html#3. Accessed on 11 November 2016
Lindner M, Hoffmann GF, Matern D. Newborn screening for disorders of fatty-acid oxidation: experience and recommendations from an expert meeting. J Inherit Metab Dis. 2010;33(5):521-6.
Bennett MJ, Santani AB. Carnitine Palmitoyltransferase 1A Deficiency. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle. 2005;1993-2022.
Fingerhut R, Röschinger W, Muntau AC, Dame T, Kreischer J, Arnecke R et al. Hepatic carnitine palmitoyltransferase I deficiency: acylcarnitine profiles in blood spots are highly specific. Clin Chem. 2001;47(10):1763-8.
American College of Medical Genetics, ACT sheet, 2009. Available at: https://rarediseases.info. nih.gov/diseases/1120/carnitine-palmitoyl-transferase-1a-deficiency. Accessed 11 November 2016.
Fraser F, Corstorphine CG, Zammit VA. Topology of carnitine palmitoyltransferase I in the mitochondrial outer membrane. Biochem J. 1997;323 (Pt 3):711-8.
Bennett MJ, Narayan SB, Santani AB. Carnitine palmitoyl transferase 1A deficiency. In Pagon RA, Bird TD, Dolan CR, editors. GeneReviews. Seattle (WA): University of Washington, Seattle. 2010;1993.
Sim KG, Wiley V, Carpenter K, Wilcken B. Carnitine palmitoyltransferase I deficiency in neonate identified by dried blood spot free carnitine and acylcarnitine profile. J Inherit Metab Dis. 2001;24(1):51-9.
Tsuburaya R, Sakamoto O, Arai N, Kobayashi H, Hasegawa Y, Yamaguchi S et al. Molecular analysis of apresymptomatic case of carnitine palmitoyl transferase I (CPT I) deficiency detected by tandem mass spectrometry newborn screening in Japan. Brain Dev. 2010;32(5):409-41.
Borch L, Lund AM, Wibrand F. Normal Levels of Plasma Free Carnitine and Acylcarnitines in Follow-Up Samples from a Presymptomatic Case of Carnitine Palmitoyl Transferase 1 (CPT1) Deficiency Detected Through Newborn Screening in Denmark. JIMD Rep. 2012;3:11-5.
Bennett MJ, Boriack RL, Narayan S, Rutledge SL, Raff ML. Novel mutations in CPT 1A define molecular heterogeneity of hepatic carnitine palmitoyltransferase I deficiency. Mol Genet Metab. 2004;82:59-63.
Brown NF, Mullur RS, Subramanian I, Esser V, Bennett MJ, Saudubray JM, et al., Molecular characterization of L-CPT I deficiency in six patients: insights into function of the native enzyme. J Lipid Res. 2001;42(7):1134-42.
Stoler JM, Sabry MA, Hanley C, Hoppel CL, Shih VE. Successful long-term treatment of hepatic carnitine palmitoyl transferase I deficiency and a novel mutation. J Inherit Metab Dis. 2004;27(5):679-84.
Korman SH, Waterham HR, Gutman A, Jakobs C, Wanders RJ.Novel metabolic and molecular findings in hepatic carnitine palmitoyltransferase I deficiency. Mol Genet Metab. 2005;86(3):337-43.
Collins SA, Sinclair G, McIntosh S, Bamforth F, Thompson R, Sobol I et al. Carnitine palmitoyl transferase 1A (CPT1A) P479L prevalence in live new borns in Yukon, Northwest Territories, and Nunavut. Mol Genet Metab. 2010;101:200-4.
Prasad C, Johnson JP, Bonnefont JP, Dilling LA, Innes AM, Haworth JC et al. Hepatic carnitine palmitoyl transferase 1 (CPT1 A) deficiency in North American Hutterites (Canadian and American): evidence for a founder effect and results of a pilot study on a DNA based newborn screening program. Mol Genet Metab. 2001;73:55-63.
Brown NF, Mullur RS, Subramanian I, Esser V, Bennett MJ, Saudubray JM et al. Molecular characterization of L-CPT I deficiency in six patients: insights in to function of the native enzyme. J Lipid Res. 2001;42:1134-42.
The 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature. 2015;526(7571):68-74.
Exome Variant Server, NHLBI GO Exome Sequencing Project (ESP), Seattle, WA. Available at: http://evs.gs.washington.edu/EVS/. Accessed on 12 December 2021.
Nagasaki M. Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals. Nat Commun. 2015;6:8018.
Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, Sirotkin K. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 2001;29(1):308-11.
Bonnefont JP, Djouadi F, Prip-Buus C, Gobin S, Munnich A, Bastin J. Carnitine palmitoyltransferases 1 and 2: biochemical, molecular and medical aspects. Mol Aspects Med. 2004;25:495-520.
Lee BH, Kim YM, Kim JH, Kim GH, Kim JM, Kim JH et al. Atypical manifestation of carnitine palmitoyl ransferase 1A deficiency: hepatosplenomegaly and ne phromegaly. J Pediatr Gastroenterol Nutr. 2015;60:e19-22.
Choi JS, Yoo HW, Lee KJ, Ko JM, Moon JS, Ko JS. Novel Mutations in the CPT1A Gene Identified in the Patient Presenting Jaundice as the First Manifestation of Carnitine Palmitoyltransferase 1A Deficiency. Pediatr Gastroenterol Hepatol Nutr. 2016;19(1):76-81.
Morris AA, Olpin SE, Bennett MJ, Santani A, Stahl Schmidt J, McClean P. Cholestatic jaundice associated with carnitine palmitoyltransferase IA deficiency. JIMD Rep. 2013;7:27-9.
Greenberg CR, Dilling LA, Thompson GR, Seargeant LE, Haworth JC, Phillips S et al. The paradox of the carnitine palmitoyltransferase type Ia P479L variant in Canadian Aboriginal populations. Mol Genet Metab. 2009;96:201-7.
Falik-Borenstein ZC, Jordan SC, Saudubray JM, Brivet M, Demaugre F, Edmond J et al. Brief report: renal tubular acidosis in carnitine palmitoyltransferase type 1 deficiency N Engl J Med. 1992;327:24-7.
