Improved inflammatory bowel disease, wound healing and normal oxidative burst under treatment with empagliflozin in glycogen storage disease type Ib

BACKGROUND: Glycogen storage disease type Ib (GSD Ib) is a rare inborn error of glycogen metabolism due to mutations in SLC37A4. Besides a severe form of fasting intolerance, the disorder is usually associated with neutropenia and neutrophil dysfunction causing serious infections, inflammatory bowel disease, oral, urogenital and perianal lesions as well as impaired wound healing. Recently, SGLT2 inhibitors such as empagliflozin that reduce the plasma levels of 1,5-anhydroglucitol have been described as a new treatment option for the neutropenia and neutrophil dysfunction in patients with GSD Ib. RESULTS: We report on a 35-year-old female patient with GSD Ib who had been treated with G-CSF for neutropenia since the age of 9. She had a large chronic abdominal wound as a consequence of recurrent operations due to complications of her inflammatory bowel disease. Treatment with 20 mg empagliflozin per day resulted in normalisation of the neutrophil count and neutrophil function even after termination of G-CSF. The chronic abdominal wound that had been unchanged for 2 years before the start of empagliflozin nearly closed within 12 weeks. No side effects of empagliflozin were observed. CONCLUSION: SGLT2 inhibitors are a new and probably safe treatment option for GSD Ib-associated neutropenia and neutrophil dysfunction. We hypothesize that restoration of neutrophil function and normalisation of neutrophil apoptosis leads to improvement of wound healing and ameliorates symptoms of inflammatory bowel disease

Successful pregnancy in maple syrup urine disease: a case report and review of the literature

Abstract Background Maple syrup urine disease (MSUD) is an autosomal recessive disorder of branched-chain amino acid metabolism. Patients with MSUD are at risk of life-threatening metabolic decompensations with ketoacidosis and encephalopathy. These episodes are often triggered by physiological stress. Only few cases of pregnancies in MSUD mothers have been reported so far. Case presentation We present the favorable outcome of a pregnancy in a woman with classical MSUD. She presented in the metabolic outpatient clinic in week 7 of gestation. Branched-chain amino acid concentrations were measured at least weekly to adjust dietary leucine intake. Despite excellent compliance, leucine concentrations frequently exceeded the target value of < 300 μmol/L during the first trimester. From the second trimester until delivery, protein and leucine intake increased continuously to about threefold compared to pre-pregnancy values. To maximize patient safety during delivery and the postpartum period, a detailed plan including peripartal infusion therapy, dietary recommendations and monitoring parameters was developed. Primary Caesarean section was performed in week 38 of gestation, and the patient gave birth to a healthy girl. Lactation was successfully implemented. Leucine levels were maintained within the target range throughout the complete postpartum period. In addition to our case, we give an overview about all cases of pregnancies in MSUD mothers published so far. Conclusions Management of pregnancy, delivery, postpartum period and lactation may be challenging in patients with MSUD. Careful monitoring and interdisciplinary collaboration is essential to minimize the risk of metabolic crisis, especially after delivery

Additional file 1: of Successful pregnancy in maple syrup urine disease: a case report and review of the literature

Table S1. MSUD diet prior to conception (leucine intake 600 mg/day). (DOCX 15 kb

Additional file 3: of Successful pregnancy in maple syrup urine disease: a case report and review of the literature

Table S3. MSUD diet at the day of delivery (leucine intake 200 mg/day, additional to a high-caloric infusion therapy). (DOCX 15 kb

Additional file 2: of Successful pregnancy in maple syrup urine disease: a case report and review of the literature

Table S2. MSUD diet at the end of pregnancy (leucine intake 2400 mg/day). (DOCX 15 kb

Elevated Plasma Vitamin B12 in Patients with Hepatic Glycogen Storage Diseases

Background: Hepatic glycogen storage diseases (GSDs) are inborn errors of metabolism affecting the synthesis or breakdown of glycogen in the liver. This study, for the first time, systematically assessed vitamin B(12)status in a large cohort of hepatic GSD patients.Methods: Plasma vitamin B-12, total plasma homocysteine (tHcy) and methylmalonic acid concentrations were measured in 44 patients with hepatic GSDs and compared to 42 healthy age- and gender-matched controls. Correlations of vitamin B(12)status with different disease markers of GSDs (including liver transaminase activities and triglycerides) as well as the vitamin B(12)intake were studied.Results: GSD patients had significantly higher plasma vitamin B(12)concentrations than healthy controls (p= 0.0002). Plasma vitamin B(12)concentration remained elevated in GSD patients irrespective of vitamin B(12)intake. Plasma vitamin B(12)concentrations correlated negatively with triglyceride levels, whereas no correlations were detected with liver transaminase activities (GOT and GPT) in GSD patients. Merging biomarker data of healthy controls and GSD patients showed a positive correlation between vitamin B(12)status and liver function, which suggests complex biomarker associations. A combined analysis of biomarkers permitted a reliable clustering of healthy controls versus GSD patients.Conclusions: Elevated plasma concentration of vitamin B-12(irrespective of B(12)intake) is a common finding in patients with hepatic GSD. The negative correlation of plasma vitamin B(12)with triglyceride levels suggests an influence of metabolic control on the vitamin B(12)status of GSD patients. Elevated vitamin B(12)was not correlated with GOT and GPT in our cohort of GSD patients. Merging of data from healthy controls and GSD patients yielded positive correlations between these biomarkers. This apparent dichotomy highlights the intrinsic complexity of biomarker associations and argues against generalizations of liver disease and elevated vitamin B(12)in blood. Further studies are needed to determine whether the identified associations are causal or coincidental, and the possible impact of chronically elevated vitamin B(12)on GSD

Effect of dietary regime on metabolic control in phenylketonuria: Is exact calculation of phenylalanine intake really necessary?

Background: A phenylalanine (Phe) restricted dietary management is required in phenylketonuria (PKU) to maintain good metabolic control. Nevertheless, five different models of dietary regimes, which differ in their accuracy of Phe documentation, are used. To investigate the effect of the dietary regime on metabolic control, a multicenter evaluation was performed. Patients/Methods: 149 patients (max. 800 mg Phe-intake/day; 108 children aged 1–9 years and 41 adolescents aged 10–15 years) could be included. They were separated according to age and dietary regime, revealed by a questionnaire on dietary habits. Dietary regimes vary from daily strict calculation of all Phe-intake (group 1) to a rather loose regime only estimating Phe-intake and including high protein food (group 5). Data were analyzed with respect to metabolic control (Phe-concentrations, Phe-concentrations above upper recommended limit during 6 months before the interview), Phe-intake (mg/day) and age (years). Results: Median Phe-concentrations in children did not differ significantly among diet groups (group 1: 161; 2: 229, 3: 236, 4: 249, 5: 288 μmol/l, p = 0.175). However, exact daily Phe calculation led to significantly lower percentage of Phe concentrations above the upper recommended limit (group 1: 17, 2: 50, 3: 42, 4: 50, 5: 75%, p = 0.035). All included patients showed good to acceptable metabolic control. Patients on the dietary regime with the least accuracy, consuming also high protein foods, showed the poorest metabolic control. Median Phe concentrations of all other groups remained within recommended ranges, including from groups not calculating special low protein foods, fruit and vegetables and using a simplified system of recording Phe-intake. In adolescents no significant differences among diet groups were revealed. Conclusion: Exact calculation of Phe content of all food is not necessary to achieve good metabolic control in children and adolescents with PKU. Excluding special low protein food, as well as fruit and vegetables from calculation of Phe-intake has no impact on metabolic control. However including protein rich food into the diet and simply estimating all Phe-intake appears insufficient. The simplification of dietary regime may be helpful in enhancing acceptability and feasibility

Preventing maternal phenylketonuria (PKU) syndrome: important factors to achieve good metabolic control throughout pregnancy

Background!#!Insufficient metabolic control during pregnancy of mothers with phenylketonuria (PKU) leads to maternal PKU syndrome, a severe embryo-/fetopathy. Since maintaining or reintroducing the strict phenylalanine (Phe) limited diet in adults with PKU is challenging, we evaluated the most important dietary and psychosocial factors to gain and sustain good metabolic control in phenylketonuric women throughout pregnancy by a questionnaire survey with 38 questions concerning therapy feasibility. Among them, the key questions covered 5 essential items of PKU care as follows: General information about maternal PKU, PKU training, diet implementation, individual metabolic care, personal support. In addition, all participating PKU mothers were asked to estimate the quality of their personal metabolic control of the concluded pregnancies. 54 PKU mothers with 81 pregnancies were approached at 12 metabolic centers in Germany and Austria were included. According to metabolic control, pregnancies of PKU women were divided in two groups: group 'ideal' (not more than 5% of all blood Phe concentrations during pregnancy &amp;gt; 360 µmol/l; n = 23) and group 'suboptimal' (all others; n = 51).!##!Results!#!The demand for support was equally distributed among groups, concerning both amount and content. Personal support by the direct social environment (partner, family and friends) ('suboptimal' 71% vs 'ideal' 78%) as well as individual metabolic care by the specialized metabolic center (both groups around 60%) were rated as most important factors. The groups differed significantly with respect to the estimation of the quality of their metabolic situation (p &amp;lt; 0.001). Group 'ideal' presented a 100% realistic self-assessment. In contrast, group 'suboptimal' overestimated their metabolic control in 53% of the pregnancies. Offspring of group 'suboptimal' showed clinical signs of maternal PKU-syndrome in 27%.!##!Conclusion!#!The development of training programs by specialized metabolic centers for females with PKU in child bearing age is crucial, especially since those mothers at risk of giving birth to a child with maternal PKU syndrome are not aware of their suboptimal metabolic control. Such programs should provide specific awareness training for the own metabolic situation and should include partners and families