Cytosolic phosphoenolpyruvate carboxykinase deficiency: Expanding the clinical phenotype and novel laboratory findings.

Cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) deficiency due to the homozygous PCK1 variant has recently been associated with childhood-onset hypoglycemia with a recognizable pattern of abnormal urine organic acids. In this study, 21 children and 3 adult patients with genetically confirmed PEPCK-C deficiency were diagnosed during the years 2016 to 2019 and the available biochemical and clinical data were collected. All patients were ethnic Finns. Most patients (22 out of 24) had a previously published homozygous PCK1 variant c.925G>A. Two patients had a novel compound heterozygous PCK1 variant c.925G>A and c.716C>T. The laboratory results showed abnormal urine organic acid profile with increased tricarboxylic acid cycle intermediates and inadequate ketone body production during hypoglycemia. The hypoglycemic episodes manifested predominantly in the morning. Infections, fasting or poor food intake, heavy exercise, alcohol consumption, and breastfeeding were identified as triggering factors. Five patients presented with neonatal hypoglycemia. Hypoglycemic seizures occurred in half of the patients (12 out of 24). The first hypoglycemic episode often occurred at the age of 1-2 years, but it sometimes presented at a later age, and could re-occur during school age or adulthood. This study adds to the laboratory data on PEPCK-C deficiency, confirming the recognizable urine organic acid pattern and identifying deficient ketogenesis as a novel laboratory finding. The phenotype is expanded suggesting that the risk of hypoglycemia may continue into adulthood if predisposing factors are present.

Cryopyrin-associated periodic syndrome in early childhood can be successfully treated with interleukin-1 blockades.

Cryopyrin-associated periodic syndrome (CAPS) is caused by a mutation in the NLRP3 gene encoding cryopyrin production. Overproduction of interleukin-1 (IL-1) leads to symptoms that are associated with elevated inflammatory markers, including periodic fever and a rash. We provide a clinical overview of CAPS in children, including three Finnish case studies. CONCLUSION: When CAPS has been diagnosed, an IL-1 blockade with biological should be introduced to lessen the symptoms and to prevent the progression of organ damage.

First-year purchases of disease-modifying drugs of incident patients with chronic juvenile arthritis in Finland.

OBJECTIVES: To establish a nationwide overview on drug treatment of juvenile idiopathic arthritis (JIA), which is the most frequent form of chronic arthritis (JA) in children and adolescents. The emphasis is on the first 12 months after diagnosis, and any changes in medication practices during the early years of the present millennium are registered. METHODS: The Social Insurance Institution (SII) in Finland keeps a national register on individuals granted with a special reimbursement for medication of defined chronic diseases. From that register, we identified by the ICD-code of M08 all JA patients aged 16 years or under with an index day from 2000 through 2007. The prescription register of the SII showed the medication purchased for the patients. The register does not cover infused medications given in hospitals. We evaluated the first disease year's medication and the treatment strategy of the very first three months. RESULTS: Within our study period 2000-2007, the proportion of patients using methotrexate during the first year of treatment increased from 54 to 72% (p<0.001). The combination of two or more DMARDs became more popular (increased from 16 to 21%) as the initial treatment strategy. These changes parallel a decrease in per oral glucocorticoids. The proportion of JA patients receiving TNFα-blockers during the first year after diagnose reached the level of about 5% during the years 2004 to 007. CONCLUSIONS: The drug treatment of patients with recent onset JA has become more intensive during the course of the new millennium in Finland, a fact expected to improve the disease outcome.