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Novel missense variants in PCK1 gene cause cytosolic PEPCK deficiency with growth failure from inadequate caloric intake

Journal of Human Genetics volume 66, pages 321–325 (2021)Cite this article

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Abstract

Cytosolic PEPCK deficiency (PCKDC) is a rare autosomal recessive inborn error of metabolism, which can present with hypoglycemia, lactic acidosis, and liver failure. It is caused by biallelic pathogenic variants in the PCK1 gene. Only four PCK1 variants have been previously reported in seven patients with PCKDC, and their clinical course of this condition has not been well characterized. Here, we report a Hispanic male with novel biallelic PCK1 variants, p.(Gly430Asp) and p.(His496Gln), who had a unique clinical presentation. He presented with a new onset of growth failure, elevated blood lactate, transaminitis, and abnormal urine metabolites profile, but he has not had documented hypoglycemia. Growth restriction happened due to insufficient caloric intake, and it was improved with nutritional intervention. PCKDC is a manageable disorder and therefore appropriate nutritional and clinical suspicion from typical lab abnormalities which lead to molecular confirmation tests are essential to prevent poor clinical outcomes.

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Acknowledgements

We would like to thank the patient and his family for their contribution to this study.

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Authors and Affiliations

  1. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Kimihiko Oishi, Casey Siegel, Emalyn E. Cork, Hongjie Chen & Eri Imagawa

  2. Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Kimihiko Oishi, Casey Siegel & Emalyn E. Cork

  3. Mount Sinai Genomics, Inc., DBA Sema4, New York, NY, USA

    Hongjie Chen

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  1. Kimihiko Oishi
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  2. Casey Siegel
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Correspondence to Kimihiko Oishi.

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HC is a paid employee of Sema4. The other authors have no conflicts of interest to declare.

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Oishi, K., Siegel, C., Cork, E.E. et al. Novel missense variants in PCK1 gene cause cytosolic PEPCK deficiency with growth failure from inadequate caloric intake. J Hum Genet 66, 321–325 (2021). https://doi.org/10.1038/s10038-020-00823-8

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  • DOI: https://doi.org/10.1038/s10038-020-00823-8

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