Correction to: Novel mutation in carnitine palmitoyltransferase 1A detected through newborn screening for a presymptomatic case in China: a case report

Abstract Background Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a rare mitochondrial fatty acid oxidation (FAO) disorder that results in hypoketotic hypoglycemia and hepatic encephalopathy. It is caused by mutation in CPT1A. To date, only two symptomatic cases of CPT1A deficiency have been reported in China. Case presentation A newborn male, without any disease-related clinical manifestations, was diagnosed with CPT1A deficiency through newborn screening. Increased free carnitine levels and a significantly increased C0/(C16 + C18) ratio were detected by tandem mass spectrometry, and subsequently, mutations in CPT1A were found by gene sequence analysis. The patient was advised a low-fat, high-protein diet and followed up regularly. During three-years of follow-up since, the patient showed normal growth velocity and developmental milestones. Whole-exome sequence identified two mutations, c.2201 T > C (p.F734S) and c.1318G > A (p.A440T), in the patient. The c.2201 T > C mutation, which has been reported previously, was inherited from his father, while the c.1318G > A, a novel mutation, was inherited from his mother. The amino acid residues encoded by original sequences are highly conserved across different species. These mutations slightly altered the three-dimensional structure of the protein, as analyzed by molecular modeling, suggesting that they may be pathogenic. Conclusion This is the first case of CPT1A deficiency detected through newborn screening based on diagnostic levels of free carnitine, in China. Three years follow-up suggested that early diagnosis and diet management may improve the prognosis in CPT1A patient. In addition, we identified a novel mutation c.1318G > A in CPT1A,and a possible unique to Chinese lineage mutation c.2201 T > C. Our findings have expanded the gene spectrum of this rare condition and provided a basis for family genetic counseling and prenatal diagnosis.

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Novel mutation in carnitine palmitoyltransferase 1A detected through newborn screening for a presymptomatic case in China：A case report and literature review

10.21203/rs.3.rs-99431/v1 ◽

2020 ◽

Author(s):

Haining Fang ◽

Yi Gan ◽

Fei Yu

Keyword(s):

Newborn Screening ◽

Novel Mutation ◽

Clinical Manifestations ◽

Carnitine Palmitoyltransferase ◽

Free Carnitine ◽

Dimensional Structure ◽

Acid Oxidation ◽

Missense Mutations ◽

First Case ◽

Mitochondrial Fatty Acid

Abstract Background：Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a rare mitochondrial fatty acid oxidation (FAO) disorder that results in hypoketotic hypoglycemia and hepatic encephalopathy. It is caused by mutation in CPT1A. To date, only two symptomatic cases of CPT1A deficiency have been reported in China.Case presentation: A newborn male, without any disease-related clinical manifestations, was diagnosed with CPT1A deficiency through newborn screening. Increased free carnitine levels and a significantly increased C0/(C16+C18) ratio were detected at 3 days of age, and subsequently, mutations in CPT1A were found by gene sequence analysis. The patient was advised a low-fat, high-protein diet and followed up regularly. During three-years of follow-up since, the patient showed normal growth velocity and developmental milestones. Whole-exome sequencing identified two mutations, c.2201T >C (p.F734S) and c.1318G>A (p.A440T), in the patient. The c.2201T >C mutation, which has been reported previously, was inherited from his father, while the c.1318G>A, a novel mutation, was inherited from his mother. The amino acid residues encoded by original sequences are highly conserved across different species. These mutations slightly altered the three-dimensional structure of the protein, as analyzed by molecular modeling, suggesting that they may be pathogenic.Conclusion: This is the first case of CPT1A deficiency detected through newborn screening based on diagnostic levels of free carnitine, in China. We identified two missense mutations, c.2201T >C and novel c.1318G>A, in the patient. Our findings have expanded the gene spectrum of this rare condition and provided a basis for family genetic counseling and prenatal diagnosis.

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Rhabdomyolysis, Acute Kidney Injury, and a Novel Frameshift Mutation in a Child with Glutaric Acidemia Type I

Nephron ◽

10.1159/000515012 ◽

2021 ◽

pp. 1-6

Author(s):

Linlin Huang ◽

Ting Shi ◽

Ying Li ◽

Xiaozhong Li

Keyword(s):

Acute Kidney Injury ◽

Case Report ◽

Frameshift Mutation ◽

Novel Mutation ◽

Kidney Injury ◽

Febrile Illness ◽

Type I ◽

Continuous Venovenous Hemodiafiltration ◽

Glutaric Acidemia Type I ◽

Acute Decompensation

This is a case report of a girl with glutaric acidemia type I (GA-I) who experienced rhabdomyolysis and acute kidney injury (AKI). Her first acute metabolic crisis occurred at the age of 5 months, which mainly manifested as irritable crying, poor appetite, and hyperlactatemia. Mutation analysis showed 2 pathogenic mutations in the glutaryl-CoA dehydrogenase (GCDH) gene, which were c.383G>A (p.R128Q) and c.873delC (p.N291Kfs*41), the latter of which is a novel frameshift mutation of GA-I. She had a febrile illness at the age of 12 months, followed by AKI and severe rhabdomyolysis. Four days of continuous venovenous hemodiafiltration (CVVHDF) helped to overcome this acute decompensation. This case report describes a novel mutation in the GCDH gene, that is, c.873delC (p.N291Kfs*41). Also, it highlights the fact that patients with GA-I have a high risk of rhabdomyolysis and AKI, which may be induced by febrile diseases and hyperosmotic dehydration; CVVHDF can help to overcome this acute decompensation.

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