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.Peer reviewe

Diet during pregnancy:dietary patterns and weight gain rate among Finnish pregnant women

Abstract Proper nutrition and optimal weight status in pregnancy are important for both the mother and her child. The present study was aimed at assessment of maternal food and nutrient intake, dietary supplement use, dietary patterns, and weight during pregnancy. Additionally, associations between maternal weight, socio-demographic and perinatal factors and advanced beta cell autoimmunity in the offspring were examined. The results from a one-year cohort of mothers entering the ongoing Type 1 Diabetes Prediction and Prevention (DIPP) study in 1998–99 (n =  797) suggested that healthy food choices were positively correlated with maternal age and education. Dietary supplements were used by 85% of the women. However, the intake of vitamin D did not meet the recommendation and folic acid intake was inadequate in 44% of the pregnant women when both food and supplementation intakes were taken into account. Seven dietary patterns were identified in 3730 pregnant women who entered the DIPP study between 1997 and 2002. The ‘healthy’, the ‘low-fat foods’ and the ‘alcohol and butter’ dietary patterns were positively associated with maternal age and education. The ‘fast food’ dietary pattern was positively associated and the ‘alcohol and butter’ pattern was inversely associated with the rate of maternal weight gain during pregnancy. Altogether, 4093 children and their mothers comprised the study population in which the relationships between maternal initial body mass index, weight gain rate, and the development of beta cell autoimmunity in the offspring were examined. Maternal weight status during pregnancy was not related to the risk of advanced beta cell autoimmunity. A higher level of maternal education was significantly associated with a decreased risk of advanced beta cell autoimmunity in children. More attention should be paid to nutritional guidance among Finnish pregnant women, especially as regards young and less well educated women. Dietary patterns may be useful for risk group identification and they may offer a framework for further research concerning diet and health outcomes among mothers and their children

Seven distinct dietary patterns identified among pregnant Finnish women--associations with nutrient intake and sociodemographic factors.

OBJECTIVES: To identify and describe dietary patterns in a cohort of pregnant women and investigate whether the dietary patterns are associated with dietary intake and sociodemographic factors. DESIGN: Mothers entering the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study in 1997-2002 were retrospectively asked to complete a food-frequency questionnaire concerning their diet during pregnancy. Principal components analysis was used to identify dietary patterns. SETTING: Finland. SUBJECTS: Subjects were 3730 women with a newborn infant carrying increased genetic susceptibility to type 1 diabetes mellitus. RESULTS: Seven factors were identified and named. Energy intake correlated positively with 'Healthy', 'Fast food', 'Traditional bread', 'Traditional meat' and 'Coffee' patterns and inversely with the 'Alcohol and butter' pattern. Intake of dietary fibre correlated positively with 'Healthy', 'Traditional bread' and 'Low-fat foods' patterns and inversely with the 'Alcohol and butter' pattern. The seven dietary patterns seemed to account for relatively large proportions of the variance in energy and nutrient intakes except for the intake of vitamin D, vitamin C, carotenoids and calcium. Maternal age and higher level of education were associated with higher scores on 'Healthy', 'Low-fat foods' and 'Alcohol and butter' patterns. CONCLUSION: Principal components analysis produced seven dietary patterns which may be useful for further research concerning maternal diet and health outcomes among both mothers and their offspring

Study design.

<p>Study design.</p

Risks of carriage of <i>Haemophilus influenzae</i> (91/1006, 9%), <i>Moraxella catarrhalis</i> (179/1006, 18%) and <i>Staphylococcus aureus</i> (261/1006, 26%) attached to the food groups¹.

<p>Results of the multivariate logistic regression analysis.</p>1<p>Adjusted for age, gender and maternal education level.</p

Dietary groups revealed by the factorial analysis¹.

1<p>The dietary groups represent factors revealed by principal components analysis (PCA) with varimax rotation among 1006 children. A total of 25 food items were used in the analysis.</p

Characteristics of the children (n = 1006).

1<p>Overweight means ISO-BMI between 25 and 30, obesity means ISO-BMI more than 30.</p>2<p>41 of the children received a 10-valent vaccination, 13 received a 13-valent vaccination, 5 received a 23-valent vaccination, and the vaccination data for 26 children were unknown. Pneumococcal 10-valent vaccination is now part of the Finnish national immunization programme for children born after 1st June 2010.</p>3<p>Any smoking by the mother or father at the time of the survey.</p>4<p>Number of AOM episodes reported by the parents.</p

Risks of pneumococcal carriage and AOM episodes attached to the food groups¹.

<p>Results of the multivariate logistic regression analysis and general linear model (GLM) analysis.</p>1<p>Adjusted for age, gender and maternal educational level.</p>2<p>Regression coefficient, values below zero indicate decreased risk and those above zero increased risk.</p