Diagnosis, treatment, management and monitoring of patients with tyrosinaemia type 1: Consensus group recommendations from the German-speaking countries.

Hepatorenal tyrosinaemia (HT1) is an autosomal recessive disorder of tyrosine degradation resulting in hepatic and renal dysfunction, neurological sequelae may occur in some patients. The use of nitisinone (NTBC) has revolutionised treatment and outcome of this disorder. NTBC has to be combined with a low protein diet.

Neurological outcome in long-chain hydroxy fatty acid oxidation disorders.

Objective: This study aims to elucidate the long-term benefit of newborn screening (NBS) for individuals with long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP) deficiency, inherited metabolic diseases included in NBS programs worldwide.

Methods: German national multicenter study of individuals with confirmed LCHAD/MTP deficiency identified by NBS between 1999 and 2020 or selective metabolic screening. Analyses focused on NBS results, confirmatory diagnostics, and long-term clinical outcomes.

Management, vaccination status and COVID-19 morbidity of patients with Gaucher disease in Germany during the COVID-19 pandemic.

Background: Continuation of standard management of Gaucher disease (GD) has been challenging during the COVID-19 pandemic, resulting in infrequent/missed infusions and follow-up appointments. Little data are available on the consequences of these changes and on the SARS-CoV-2 vaccinations in German GD patients.

Methods: A survey with 22 questions about GD management during the pandemic was sent to 19 German Gaucher centres.

Radiofrequency Pulmonary Vein Isolation without Esophageal Temperature Monitoring: Contact-Force Characteristics and Incidence of Esophageal Thermal Damage.

Esophageal thermal lesions following pulmonary vein isolation (PVI) for atrial fibrillation (AF) potentially harbor lethal complications. Radiofrequency (RF)-PVI using contact force-technology can reduce collateral damage. We evaluated the incidence of endoscopically detected esophageal lesions (EDEL) and the contribution of contact force to esophageal lesion formation without esophageal temperature monitoring.

Percutaneous transhepatic or endoscopic ultrasound-guided biliary drainage in malignant distal bile duct obstruction using a self-expanding metal stent: Study protocol for a prospective European multicenter trial (PUMa trial).

Background: Endoscopic ultrasound-guided biliary drainage (EUS-BD) was associated with better clinical success and a lower rate of adverse events (AEs) than fluoroscopy-guided percutaneous transhepatic biliary drainage (PTBD) in recent single center studies with mainly retrospective design and small case numbers (< 50). The aim of this prospective European multicenter study is to compare both drainage procedures using ultrasound-guidance and primary metal stent implantation in patients with malignant distal bile duct obstruction (PUMa Trial).

Methods: The study is designed as a non-randomized, controlled, parallel group, non-inferiority trial.

Recommendations for diagnosing and managing individuals with glutaric aciduria type 1: Third revision.

Glutaric aciduria type 1 is a rare inherited neurometabolic disorder of lysine metabolism caused by pathogenic gene variations in GCDH (cytogenic location: 19p13.13), resulting in deficiency of mitochondrial glutaryl-CoA dehydrogenase (GCDH) and, consequently, accumulation of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid and glutarylcarnitine detectable by gas chromatography/mass spectrometry (organic acids) and tandem mass spectrometry (acylcarnitines). Depending on residual GCDH activity, biochemical high and low excreting phenotypes have been defined.

Impact of pregnancy planning and preconceptual dietary training on metabolic control and offspring's outcome in phenylketonuria.

To prevent maternal phenylketonuria (PKU) syndrome low phenylalanine concentrations (target range, 120-360 μmol/L) during pregnancy are recommended for women with PKU. We evaluated the feasibility and effectiveness of current recommendations and identified factors influencing maternal metabolic control and children's outcome. Retrospective study of first successfully completed pregnancies of 85 women with PKU from 12 German centers using historical data and interviews with the women.

Swelling-induced upregulation of miR-141-3p inhibits hepatocyte proliferation.

Background & Aims: MicroRNAs (miRNAs) act as a regulatory mechanism on a post-transcriptional level by repressing gene transcription/translation and play a central role in the cellular stress response. Osmotic changes occur in a variety of diseases including liver cirrhosis and hepatic encephalopathy. Changes in cell hydration and alterations of the cellular volume are major regulators of cell function and gene expression.

Diagnosis and management of secondary causes of steatohepatitis.

The term non-alcoholic fatty liver disease (NAFLD) was originally coined to describe hepatic fat deposition as part of the metabolic syndrome. However, a variety of rare hereditary liver and metabolic diseases, intestinal diseases, endocrine disorders and drugs may underlie, mimic, or aggravate NAFLD. In contrast to primary NAFLD, therapeutic interventions are available for many secondary causes of NAFLD.

Hepatorenal Tyrosinaemia: Impact of a Simplified Diet on Metabolic Control and Clinical Outcome.

: Tyrosinaemia type 1 is a rare inherited metabolic disease caused by an enzyme defect in the tyrosine degradation pathway. It is treated using nitisinone and a low-protein diet. In a workshop in 2013, a group of nutritional specialists from Germany, Switzerland and Austria agreed to advocate a simplified low-protein diet and to allow more natural protein intake in patients with tyrosinaemia type 1.

Everyday Life, Dietary Practices, and Health Conditions of Adult PKU Patients: A Multicenter, Cross-Sectional Study.

Background: Only few data on dietary management of adult phenylketonuria (PKU) patients are published.

Objectives: This study aimed to assess living situation, dietary practices, and health conditions of early-treated adult PKU patients.

Methods: A total of 183 early-treated PKU patients ≥18 years from 8 German metabolic centers received access to an online survey, containing 91 questions on sociodemographic data, dietary habits, and health conditions.

Cardiometabolic risk factor clustering in patients with deficient branched-chain amino acid catabolism: A case-control study.

Classical organic acidemias (OAs) result from defective mitochondrial catabolism of branched-chain amino acids (BCAAs). Abnormal mitochondrial function relates to oxidative stress, ectopic lipids and insulin resistance (IR). We investigated whether genetically impaired function of mitochondrial BCAA catabolism associates with cardiometabolic risk factors, altered liver and muscle energy metabolism, and IR.

[Secondary causes of fatty liver disease - an update on pathogenesis, diagnosis and treatment strategies].

Secondary causes of fatty liver disease are important to recognize since specific therapy options are available for some of these causes. Common causes of secondary fatty liver disease comprise hepatitis C virus infection (HCV), endocrinological diseases, nutritional and intestinal diseases as well as genetic liver and metabolic diseases. Certain drugs may also predispose to the development of fatty liver disease.

Incidental F-FDG uptake in the colon: value of contrast-enhanced CT correlation with colonoscopic findings.

Objectives: To evaluate the impact of morphological information derived from contrast-enhanced CT in the characterization of incidental focal colonic uptake in F-FDG PET/CT examinations.

Methods: A total of 125 patients (female: n = 53, male: n = 72) that underwent colonoscopy secondary to contrast-enhanced, full-dose PET/CT without special bowel preparation were included in this retrospective study. PET/CT examinations were assessed for focal colonic tracer uptake in comparison with the background.

Presenting signs and patient co-variables in Gaucher disease: outcome of the Gaucher Earlier Diagnosis Consensus (GED-C) Delphi initiative.

Background: Gaucher disease (GD) presents with a range of signs and symptoms. Physicians can fail to recognise the early stages of GD owing to a lack of disease awareness, which can lead to significant diagnostic delays and sometimes irreversible but avoidable morbidities.

Aim: The Gaucher Earlier Diagnosis Consensus (GED-C) initiative aimed to identify signs and co-variables considered most indicative of early type 1 and type 3 GD, to help non-specialists identify 'at-risk' patients who may benefit from diagnostic testing.

Hepatocellular carcinoma in Gaucher disease: an international case series.

Gaucher disease (GD) is associated with an increased risk for malignancies. Next to hematological malignancies, the development of solid tumors in several organs has been described. The liver is one of the major storage sites involved in GD pathogenesis, and is also affected by liver-specific complications.

Low Incidence of Esophageal Lesions After Pulmonary Vein Isolation Using Contact-Force Sensing Catheter Without Esophageal Temperature Probe.

Pulmonary vein isolation (PVI) is a cornerstone therapy for atrial fibrillation (AF). Although severe complications are rather rare, the development of an atrio-esophageal fistula (AEF) is a fatal complication with a very high mortality even after surgical treatment. The use of esophageal temperature probes (ETP) during PVI may protect the esophagus but it is still under debate since the ETP may also lead to esophageal lesions.

Favourable Outcome in Two Pregnancies in a Patient with 3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency.

In patients with 3-hydroxy-3-methylglutaryl(HMG)-CoA lyase deficiency (OMIM 246450), five pregnancies have been described worldwide, which were either terminated or resulted in severe metabolic sequelae during pregnancy or delivery. Here, we report on a patient with HMG-CoA lyase deficiency, who underwent two uncomplicated pregnancies. The 19-year-old patient was admitted because of recurrent vomiting and nausea.

Management and monitoring recommendations for the use of eliglustat in adults with type 1 Gaucher disease in Europe.

Purpose: In Gaucher disease, diminished activity of the lysosomal enzyme, acid β-glucosidase, leads to accumulation of glucosylceramides and related substrates, primarily in the spleen, liver, and bone marrow. Eliglustat is an oral substrate reduction therapy approved in the European Union and the United States as a first-line treatment for adults with type 1 Gaucher disease who have compatible CYP2D6 metabolism phenotypes. A European Advisory Council of experts in Gaucher disease describes the characteristics of eliglustat that are distinct from enzyme augmentation therapy (the standard of care) and miglustat (the other approved substrate reduction therapy) and recommends investigations and monitoring for patients on eliglustat therapy within the context of current recommendations for Gaucher disease management.

Understanding the natural history of Gaucher disease.

Gaucher disease is a rare and extraordinarily heterogeneous inborn error of metabolism that exhibits diverse manifestations, a broad range of age of onset of symptoms, and a wide clinical spectrum of disease severity, from lethal disease during infancy to first age of onset of symptoms in octogenarians. Before the advent of the International Collaborative Gaucher Group (ICGG) Gaucher Registry, the understanding of the natural history and phenotypic range of Gaucher disease was based on isolated case reports and small case series. Limited data hindered understanding of the full spectrum of the disease leading to some early misconceptions about Gaucher disease, notably, that nonneuronopathic (type 1) disease was a disease of adults only.

Gaucher disease and malignancy: a model for cancer pathogenesis in an inborn error of metabolism.

Clinical observations spanning almost half a century have demonstrated a consistent association of type 1 Gaucher disease (GD1) and cancers. However, the cellular and molecular bases of the association are not understood. Gaucher disease (GD) is a lysosomal storage disorder due to an inherited deficiency of acid β-glucosidase that underlies the accumulation of glucosylceramide in lysosomes of mononuclear phagocytes and immune dysregulation.

Long-term clinical outcomes in type 1 Gaucher disease following 10 years of imiglucerase treatment.

Objective: We studied the effect of long-term alglucerase/imiglucerase (Ceredase®/Cerezyme®, Genzyme, a Sanofi company, Cambridge, MA, USA) treatment on hematological, visceral, and bone manifestations of Gaucher disease type 1 (GD1).

Methods: The International Collaborative Gaucher Group (ICGG) Gaucher Registry identified GD1 patients treated with alglucerase/imiglucerase who had dose and clinical data at first infusion and after 10 years of follow-up. Data for hemoglobin, platelet count, organ volumes, bone pain, and bone crisis were analyzed.