Pathogenic Potential of a PCK1 Gene Variant in Cytosolic PEPCK Deficiency: A Compelling Case Study.

BACKGROUND Cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) deficiency is an extremely rare autosomal recessive inherited error of metabolism in which gluconeogenesis is impaired, resulting in life-threatening episodes of hypoglycemia and metabolic acidosis. The diagnosis of gluconeogenesis disorders is challenging. In the diagnostic pathway, the molecular test plays a paramount role. CASE REPORT The aim of the paper is to present the case report of a girl with recurrent episodes of severe hypoglycemia, in whom molecular diagnosis enabled the confirmation of PEPCK - C deficiency. The patient experienced 4 episodes of severe hypoglycemia. Most of them were accompanied by hyperlacticaemia, metabolic acidosis, and elevated liver enzymes. All of the metabolic decompensations were triggered by infectious agents. The episodes resolved after continuous infusion of high-dose glucose. Due to the recurrent character of the disease, a genetic condition was suspected. The differential diagnosis included metabolic and endocrinological causes of hypoglycemia. Two variants in the PCK1 gene were detected: c.265G>A p.(Glu89Lys) in exon 3 and c.925G>A p.(Gly309Arg) in exon 6. As c.925G>A p.(Gly309Arg) is a known pathogenic variant, the second variant was first described in June 2023 in the ClinVar database and described as "with unknown clinical significance". CONCLUSIONS According to the clinical symptoms observed in the presented case, the variant c.265G>A p.(Glu89Lys) in PCK1 gene should be considered likely pathogenic. We suggest considering molecular diagnostics in every patient presented with recurrent, severe hypoglycemia with accompanying liver damage as most accurate, feasible, and reliable method.

Holistic Approach to the Diagnosis and Treatment of Patients with Tumor Metastases to the Spine.

The treatment of neoplastic spine metastases requires multi-faceted assessment and an interdisciplinary approach to patients. The metastases do not show specific symptoms but are often the first confirmation of the presence of a primary tumor in a patient. The diagnostic process includes imaging and invasive procedures, e.g., biopsy. It is essential to qualify the patient for an appropriate treatment using dedicated scales. Decompression of the spinal cord is a critical issue to save or restore neurological function in a patient with spine metastases. Surgical treatment ought to meet three criteria: release spinal cord and nerve roots, restore the spine's anatomical relations, and ensure the internal stabilization of the spine. A good result from surgical treatment enables the continuation of radiotherapy, chemotherapy, hormone therapy, and targeted molecular therapy. Stereotactic radiosurgery and stereotactic body radiotherapy are more effective ways of treating spine metastases than conventional external beam radiotherapy. They allow higher doses of radiation, concentrated precisely at the tumor site. Our review summarizes the established and emerging concepts in the treatment of spine metastases. A holistic approach to the patient enables the selection of the appropriate therapy.