Heiko Brennenstuhl

Heiko Brennenstuhl
Universität Heidelberg · General pediatrics, pediatric neurology, metabolism, gastroenterology, nephrology

University Hospital Heidelberg | Center for Children and Adolescent Medicine | Doctor of Medicine (M.D.) | Master of Business Administration (MBA) | www.heikobrennenstuhl.com

About

38
Publications
10,934
Reads
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218
Citations
Citations since 2016
36 Research Items
216 Citations
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2016201720182019202020212022020406080100
Introduction
Heiko Brennenstuhl is an MD at the University Hospital for Children and Adolescents in Heidelberg, Germany, currently working as a postdoctoral researcher studying inherited metabolic disorders. He received his medical degree from the University Tübingen, where he was part of the IZKF research funding and received a DAAD stipend to study at Brown University. He holds an MBA degree in Leadership and Management in Health Care from the University of Applied Sciences in Neu-Ulm.
Additional affiliations
June 2018 - December 2020
Universität Heidelberg
Position
  • PostDoc Position
February 2012 - July 2016
University of Tuebingen
Position
  • Medical Doctor
February 2012 - July 2016
Hertie-Institute for Clinical Brain Research
Position
  • Medical Doctorate
Education
April 2010 - July 2016
University of Tuebingen
Field of study
  • Medicine

Publications

Publications (38)
Article
Full-text available
Purpose: The study aimed to define the genotypic and phenotypic spectrum of reversible acute liver failure (ALF) of infancy resulting from biallelic pathogenic TRMU variants and to determine the role of cysteine supplementation in its treatment. Methods: Individuals with biallelic (likely) pathogenic variants in TRMU were studied through an inte...
Preprint
Full-text available
The widespread use of high-throughput sequencing techniques is leading to a rapidly increasing number of disease-associated variants of unknown significance and candidate genes. Integration of knowledge concerning their genetic, protein as well as functional and conservational aspects is necessary for an exhaustive assessment of their relevance and...
Article
Full-text available
Objectives Pathogenic biallelic variants in PCK1 coding for the cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) cause PEPCK-C deficiency, a rare disorder of gluconeogenesis presenting with hypoglycemia, lactic acidosis, and hepatopathy. To date, there has been no systematic analysis of its phenotypic, biochemical, and genetic spectrum. Metho...
Article
Full-text available
Background: Phenotypic diversity and long-term health outcomes of individuals with urea cycle disorders (UCDs) have been described in detail. However, there is limited information on the burden of affected families. Methods: To evaluate the family burden of parents with children suffering from UCDs, we used validated questionnaires. Socio-demograph...
Article
Full-text available
TUBA1A tubulinopathy is a rare neurodevelopmental disorder associated with brain malformations as well as early-onset and intractable epilepsy. As pathomechanisms and genotype-phenotype correlations are not completely understood, we aimed to provide further insights into the phenotypic and genetic spectrum. We here present a multicenter case series...
Article
Given the novelty of gene replacement therapy with onasemnogene abeparvovec in spinal muscular atrophy, efficacy and safety data are limited, especially for children older than 24 months, those weighing more than 8·5 kg, and those who have received nusinersen. We aimed to provide real-world data on motor function and safety after gene replacement t...
Article
Background Given the novelty of gene replacement therapy with onasemnogene abeparvovec in spinal muscular atrophy, efficacy and safety data are limited, especially for children older than 24 months, those weighing more than 8·5 kg, and those who have received nusinersen. We aimed to provide real-world data on motor function and safety after gene re...
Article
Compound heterozygosis is the most diffuse and hardly to tackle condition in aromatic amino acid decarboxylase (AADC) deficiency, a genetic disease leading to severe neurological impairment. Here, by using an appropriate vector, we succeeded in obtaining high yields of AADC protein and characterizing two new heterodimers, T69M/S147R and C281W/M362T...
Article
Full-text available
Inherited disorders of neurotransmitter metabolism are a group of rare diseases, which are caused by impaired synthesis, transport or degradation of neurotransmitters or co-factors and result in various degrees of delayed or impaired psychomotor development. To assess the effect of neurotransmitter deficiencies on intelligence, quality of life, and...
Article
Full-text available
SYNCRIP encodes for the Synaptotagmin-binding cytoplasmic RNA-interacting protein, involved in RNA-binding and regulation of multiple cellular pathways. It has been proposed as a candidate gene for neurodevelopmental disorders (NDDs) with autism spectrum disorder (ASD), intellectual disability (ID), and epilepsy. We ascertained genetic, clinical, a...
Article
Full-text available
Objective To investigate reported extreme temperature-related catastrophic events and associated mortality on the European continent including the Russian Federation. Design Cross-sectional respecting Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria. Settings Data source: Emergency Events Database (EM-DAT)....
Article
Full-text available
Mevalonic aciduria (MVA) and Hyperimmunoglobulinemia D syndrome (HIDS) are disorders of cholesterol biosynthesis caused by variants in the MVK gene and characterized by increased urinary excretion of mevalonic acid. So far, 30 MVA patients have been reported, suffering from recurrent febrile crises and neurologic impairment. Here, we present an in-...
Article
Full-text available
Background The autosomal recessive defect of aromatic L‑amino acid decarboxylase (AADC) causes a severe combined deficiency of dopamine, serotonin and catecholamines. The clinical picture is characterized by truncal hypotonia, delayed or absent achievement of motor milestones, and oculogyric crises from infancy onwards. The response to conventional...
Article
Full-text available
Pathogenic variants in KCNA2, encoding for the voltage-gated potassium channel Kv1.2, have been identified as the cause for an evolving spectrum of neurological disorders. Affected individuals show early-onset developmental and epileptic encephalopathy, intellectual disability, and movement disorders resulting from cerebellar dysfunction. In additi...
Preprint
Full-text available
Background: Despite numbers of prescriptions filled remaining constant, expenditures for drugs are rising. Among others, this is caused by high prices for orphan drugs and advanced therapy medicinal products (ATMPs). Despite attempts by policymakers to intervene, the increasing use of these therapies poses numerous challenges on the health care sys...
Chapter
Muscular tone and movements are highly dependent on the communication of neurons and muscle cells. This complex process is achieved by neurotransmitters, chemical substances synthesized and stored in presynaptic neurons, which are released into the synaptic cleft upon specific stimuli. Neurotransmitters can traverse the synaptic cleft and bind to hi...
Article
Full-text available
Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare, monogenic disorder affecting the degradation of the main inhibitory neurotransmitter γ-amino butyric acid (GABA). Pathogenic variants in the ALDH5A1 gene that cause an enzymatic dysfunction of succinic semialdehyde dehydrogenase (SSADH) lead to an accumulation of potentially toxic m...
Preprint
Full-text available
Background: Despite a constant number of prescriptions, the expenditures of the statutory health insurance funds for pharmaceuticals are rising sharply. This is due to high prices for orphan drugs and advanced therapy medicinal products (ATMPs). Despite attempts by policymakers to intervene, such as the 2011 German Pharmaceutical Market Restructuri...
Article
Full-text available
Background Pulmonary alveolar proteinosis (PAP) is a heterogeneous condition with more than 100 different underlying disorders that need to be differentiated to target therapeutic options, which are generally limited. Methods The clinical course of two brothers with pathogenic variants in the methionyl‐tRNA synthetase (MARS)1 gene was compared to...
Article
Biallelic variants in LARS1, coding for the cytosolic leucyl-tRNA synthetase, cause infantile liver failure syndrome 1 (ILFS1). Since its description in 2012, there has been no systematic analysis of the clinical spectrum and genetic findings. Individuals with biallelic variants in LARS1 were included through an international, multicenter collabora...
Article
Background Aromatic L-amino acid decarboxylase (AADC) deficiency is a primary neurotransmitter defect of the biosynthesis of catecholamines and serotonin. The phenotype consists of varying degrees of neurological impairment, including motor and non-motor symptoms. Treatment outcomes correlate with the time point of diagnosis and treatment initiatio...
Conference Paper
Full-text available
Introduction: Aromatic L-amino-acid decarboxylase (AADC) deficiency is an inherited disorder of biogenic amine metabolism resulting in severe neurologic impairment. The diagnosis is often delayed due to unspecific symptoms and the need for complex diagnostic tools. With new treatment options, particularly gene therapy, pre-symptomatic diagnosis is...
Article
Full-text available
Succinic semialdehyde dehydrogenase deficiency (SSADH-D) is a genetic disorder that results from the aberrant metabolism of the neurotransmitter γ-amino butyric acid (GABA). The disease is caused by impaired activity of the mitochondrial enzyme succinic semialdehyde dehydrogenase. SSADH-D manifests as varying degrees of mental retardation, autism,...
Preprint
Full-text available
Succinic semialdehyde dehydrogenase deficiency (SSADH-D) is a genetic disorder that results from the aberrant metabolism of the neurotransmitter γ-amino butyric acid (GABA). The disease is caused by the impaired activity of the mitochondrial enzyme succinic semialdehyde dehydrogenase. SSADH-D manifests as varying degree of mental retardation, autis...
Article
Full-text available
Background: Aromatic L-amino-acid decarboxylase (AADC) deficiency is an inherited disorder of biogenic amine metabolism with a broad neurological phenotype. The clinical symptoms overlap with other diseases resulting in an often delayed diagnosis. Innovative disease-changing treatment options, particularly gene therapy, have emphasized the need fo...
Preprint
Full-text available
This study investigates patterns of extreme temperature-related events in Europe and its significance for the public health, with a focus on the vulnerable pediatric population. A generalized additive model of average surface temperature development for the European countries is described and discussed with an in-depth analysis of the influence of...
Conference Paper
Succinic semialdehyde dehydrogenase deficiency (SSADHD) represents a rare monogenetic, autosomal-recessive disorder causing an enzymatic block of the degradation of gamma-aminobutyric acid (GABA) due to variants in ALDH5A1. Succinic semialdehyde cannot be converted to succinate and is consecutively converted to gamma-hydroxybutyrate (GHB). The phen...
Conference Paper
Succinic semialdehyde dehydrogenase deficiency (SSADHD) is an autosomal- recessive disorder caused by variants of the ALDH5A1 gene. Symptoms include developmental delay, behavioral problems, impaired motor coordination and seizures. High concentrations of the neurotransmitter gamma-amino butyric acid (GABA) and its degradation byproduct gamma-hydro...
Article
Neurotransmitter deficiencies are rare neurological disorders with clinical onset during childhood. The disorders are caused by genetic defects in the enzymes involved in synthesis, degradation, or transport of neurotransmitters or by defects in the cofactor biosynthesis such as tetrahydrobiopterin (BH4). With the newly described DNAJC12 deficiency...
Thesis
The inhibitor of nuclear factor kappa B zeta (IκBζ) is an atypical member of the IkB protein family. Its function in regulating the activity of the transcription factor nuclear factor kappa B (NFκB) as well as its involvement in cancer-associated processes is poorly understood. In glioma patients, enhanced expression of IκBζ in tumor specimens is a...
Article
Full-text available
The inhibitor of nuclear factor kappa B zeta (IκBζ) is an atypical member of the IκB protein family. Its function in regulating the activity of the transcription factor nuclear factor kappa B (NFκB) as well as its involvement in cancer-associated processes is poorly understood. In glioma patients, enhanced expression of IκBζ in tumor specimen is as...
Article
Recent studies have demonstrated that histone deacetylase (HDAC) inhibitors (HDACi) have potential immunomodulatory activity since they affect the immune surveillance by regulating the production of cytokines, alter the activity and function of macrophages and dendritic cells (DC), regulate the transcription of a variety of immune-stimulating genes...

Questions

Questions (8)
Question
Dear all,
I am looking for a way to add position specific numeric data to a pdb file. For example, I would like to give a protein consisting of 100 amino acids additional information per position, in order to convert it later into a visualization. Is there a tool or a script to modfiy pdb files accordingly?
Thanks!
Question
Dear all,
I am looking for a way to retrieve a protein's coding sequence based on the ensembl transcript ID using BioMart and the getsequence function. Does anyone have an idea how to approach this?
Question
This question keeps me busy - is there any database or any other scientifcically valid way to determine the frequency of disease-causing variants within a given gene? Most publications on this topic usually estimate the frequency by examinination of a small group of individuals with the disease - but is there a database that collects information on this stopic?
Question
Dear all,
Whenever I load my protein .pbd file into pymol or YASARA, it is displayed as a monomer structure. Yet, in its biologically active form, it is rather a homotetramer. Is there any way I can make these programs display it this way?
Thanks,
Heiko
Question
I am looking for a software tool that helps to annotate genetic variants onto the corresponding regions of my gene of interest to identify hotspots. Does anybody know a good tool to do this task? I tried using the draw proteins extension of Bioconductor in R which didn't really give me the results I was looking for. Any help would be appreciated!
Question
Hi everyone,
I would like to use the CADD Score to determine the deleteriousness of novel genetic variants. The web interface requests a VCF file as input file type, unfortunately, I do not know how to create such a file - it seems like it is a simple text file, nevertheless, I am having trouble to generate one...
Could someone help me create such a file or guide me through the process of creating one? Any help is highly appreciated!
Heiko
Question
I am using FoldX suite as a plugin in Yasara to calculate the difference in free energy caused by specific mutants in a protein I am interested in. I end up with ΔGmut and ΔGwt and calculate ΔΔG = ΔGmut-ΔGwt. So far, so good!
However, I have to consider that my protein is a tetrameric protein. How do I implement this information in my calculations?
Any help would be really appreciated!
Question
I am looking for the gene expression data for a specific gene in the TCGA GBM dataset. If I download the whole data matrix I get tables consisting of all gene expression values that were part of the assay - however, I just want a single table consisting of the TCGA identification number, my specific gene name and the log2 expression value. Any help is really appreciated!

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Projects

Projects (5)
Project
The aim of this project is to find novel methods and techniques for the diagnosis of AADC deficiency. Newborn screening and selective screening methods are validated for their use to identify AADC deficient patients. The goal is to enable early treatment with novel therapeutic approaches, such as gene therapy.