Dirk Klee

Heinrich Heine University Düsseldorf | HHU

Neurodevelopmental disorders are major indications for genetic referral and have been linked to more than 1,500 loci including genes encoding transcriptional regulators. The dysfunction of transcription factors often results in characteristic syndromic presentations, however, at least half of these patients lack a genetic diagnosis. The implementat...

Objective Clinical-standard MRI is the imaging modality of choice for the wrist, yet limited to static evaluation, thereby potentially missing dynamic instability patterns. We aimed to investigate the clinical benefit of (dynamic) real-time MRI, complemented by automatic analysis, in patients with complete or partial scapholunate ligament (SLL) tea...

Congenital heart disease (CHD) is often associated with chronic right ventricular (RV) volume overload. Real-time magnetic resonance imaging (MRI) enables the analysis of cardiac function during free breathing. To evaluate the influence of respiration in pediatric patients with CHD and chronic RV volume overload. RV volume overload patients (n=6) a...

Classical homocystinuria is caused by pathogenic variants in the CBS gene leading to a deficiency of the vitamin B6‐dependent enzyme cystathionine beta synthase. The disease is typically associated with high blood homocysteine concentrations. Clinical features include developmental delay/intellectual disability, psychiatric problems, thromboembolis...

Real-time MRI (rt-MRI) in children is a new imaging technique that combines the advantages of US — at frame rates of up to 50 images per second — with the quality and features of MRI. Although still subject of research, it has become a standard tool in the diagnostic portfolio of two pediatric radiology departments in Germany. Based on ultrashort a...

Introduction: Mechanistic target of rapamycin complex 1 (mTORC1) regulates cell growth in response to nutritional status. Central to mTORC1 function is the Rag-GTPase heterodimer. One component of the Rag heterodimer is RagC (Ras-related GTP-binding protein C), which is encoded by the RRAGC gene. Material and methods: Genetic testing via trio ex...

Coenzyme Q10 (CoQ10) is an endogenously synthesized lipid molecule. It is best known for its role as a cofactor within the mitochondrial respiratory chain where it functions in electron transfer and ATP synthesis. However, there are many other cellular pathways that also depend on the CoQ10 supply (redox homeostasis, ferroptosis and sulfide oxidati...

Background Cardiac real-time magnetic resonance imaging (RT-MRI) provides high-quality images even during free-breathing. Difficulties in post-processing impede its use in clinical routine. Objective To demonstrate the feasibility of quantitative analysis of cardiac free-breathing RT-MRI and to compare image quality and volumetry during free-breat...

Purpose To test the feasibility of cardiac real‐time MRI in combination with retrospective gating by MR‐compatible spirometry, to improve motion control, and to allow quantification of respiratory‐induced changes during free‐breathing. Methods Cross‐sectional real‐time MRI (1.5T; 30 frames/s) using steady‐state free precession contrast during free...

While morphologic magnetic resonance imaging (MRI) is the imaging modality of choice for the evaluation of ligamentous wrist injuries, it is merely static and incapable of diagnosing dynamic wrist instability. Based on real-time MRI and algorithm-based image post-processing in terms of convolutional neural networks (CNNs), this study aims to develo...

Purpose We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata–Akhtar syndrome). Methods Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers. Resul...

Background: 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 cardiomet...

Das Strategiepapier der GPR zeigt Entwicklungsmöglichkeiten der Kinder- und Jugendradiologie als Querschnittsfach zwischen der Radiologie und der konservativen und operativen Kinder- und Jugendmedizin auf. Zitierweise

Ral (Ras-like) GTPases play an important role in the control of cell migration and have been implicated in Ras-mediated tumorigenicity. Recently, variants in RALA were also described as a cause of intellectual disability and developmental delay, indicating the relevance of this pathway to neuropediatric diseases. Here, we report the identification...

Cerebral choline metabolism is crucial for normal brain function, and its homoeostasis depends on carrier-mediated transport. Here, we report on four individuals from three families with neurodegenerative disease and homozygous frameshift mutations (Asp517Metfs*19, Ser126Metfs*8, and Lys90Metfs*18) in the SLC44A1 gene encoding choline transporter-l...

We previously reported that inactivation of the transmembrane taurine transporter (TauT or solute carrier 6a6) causes early retinal degeneration in mice. Compatible with taurine's indispensability for cell volume homeostasis, protein stabilization, cytoprotection, antioxidation, and immuno‐ and neuromodulation, mice develop multisystemic dysfunctio...

Background: Diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient (ADC) calculation is important for detecting bone marrow pathologies. Objective: To investigate age-related differences of lumbar vertebral body ADC to establish normal values for healthy children. Materials and methods: Forty-nine healthy children wi...

Osteonecrosis (ON) is a common and debilitating side effect of anti-leukemic treatment in children with acute lymphoblastic leukemia (ALL). However, the impact of leukemia itself on ON development remains elusive. We analyzed 76 children enrolled in the ongoing OPAL trial, who had magnetic resonance imaging (MRI) studies at diagnosis. MRI screening...

Background Valid detection of inflamed joints is essential for correct classification, therapeutic decisions, prognosis and assessment of treatment efficacy in juvenile idiopathic arthritis (JIA). Fluorescence optical imaging (FOI) enables visualization of inflammation in arthritis of finger and hand joints and might be used for monitoring. Method...

Purpose To determine whether signal intensity (SI) in T1 sequences as a potential indicator of gadolinium deposition increases after repeated administration of the macrocyclic gadolinium-based contrast agents (GBCAs) gadoteridol and gadoterate meglumine in a pediatric cohort. Materials and Methods This retrospective case-control study of children w...

Coexistence of different hereditary diseases is a known phenomenon in populations with a high consanguinity rate. The resulting clinical phenotypes are extremely challenging for physicians involved in the care of these patients. Here we describe a 6-year-old boy with co-occurrence of a homozygous splice defect in OSTM1, causing infantile malignant...

Background Treatment of severe diffuse congenital hyperinsulinism (CHI) without sufficient response to diazoxide is complicated by the lack of approved drugs. Therefore, patients are often hospitalized long-term or have to undergo pancreatic surgery if episodes of severe hypoglycaemia cannot be prevented. A long-acting somatostatin analogue, octreo...

Conclusion: Compared to data from the general population, our results do not indicate a significantly increased prevalence of NAFLD in this cohort, and advocate against the systematic screening for NAFLD in paediatric type 1 DM. What is Known: • Non-alcoholic fatty liver disease (NAFLD) is common in adults with type 1 DM, and paediatric patients w...

Osteonecrosis (ON) is a debilitating side effect of anti-leukemic treatment. Thus far, the role of leukemic infiltration (LI) of bone is unclear. The first 30 children aged ≥10 years, who were enrolled in the ongoing OPAL trial and had MRI studies at diagnosis and at 6 months, were analyzed. MRI revealed extensive LIs in 24 (80%) patients. The sign...

The knowledge about the genetic spectrum underlying paediatric mitochondrial diseases is rapidly growing. As a consequence, the range of neuroimaging findings associated with mitochondrial diseases became extremely broad. This has important implications for radiologists and clinicians involved in the care of these patients. Here, we provide a conde...

Background: Cerebrospinal fluid (CSF) opening pressure (OP) of ≥28 cm H2O is now considered a diagnostic criterion for Pseudotumor cerebri syndrome (PTCS) in children. However, it has been proposed that a diagnosis of "probable" PTCS can be made with an OP < 28 cm H2O if other diagnostic criteria are met. We report a group of children with probabl...

To safeguard the cell from the accumulation of potentially harmful metabolic intermediates, specific repair mechanisms have evolved. APOA1BP, now renamed NAXE, encodes an epimerase essential in the cellular metabolite repair for NADHX and NADPHX. The enzyme catalyzes the epimerization of NAD(P)HX, thereby avoiding the accumulation of toxic metaboli...

Mitochondrial aminoacyl tRNA synthetases are essential for organelle protein synthesis. Genetic defects affecting the function of these enzymes may cause pediatric mitochondrial disease. Here, we report on a child with fatal neonatal lactic acidosis and recurrent hypoglycemia caused by mutations in EARS2, encoding mitochondrial glutamyl-tRNA synthe...

Background: Childhood arterial ischemic stroke (CAIS) is increasingly recognized as an important cause of significant long-term morbidity in the pediatric population. Post stroke movement disorders, above all hemi-dystonias, are much more common in children after stroke compared to adults. However, research in this field is largely lacking. By hig...

Coenzyme Q10 (CoQ10) has an important role in mitochondrial energy metabolism by way of its functioning as an electron carrier in the respiratory chain. Genetic defects disrupting the endogenous biosynthesis pathway of CoQ10 may lead to severe metabolic disorders with onset in early childhood. Using exome sequencing in a child with fatal neonatal l...

We report our experience with duplex ultrasound in young patients with renal artery stenosis (RAS) or middle aortic syndrome (MAS) before and after surgery (1995 and 2009). Of 36 patients (mean age: 13 ± 7 y), 21 had RAS and 15 had MAS. For patients with RAS, the Vmax in the affected artery was 350 ± 111 cm/s before surgery and 145 ± 55 cm/s after...

Tracheal wall injuries are life-threatening and require immediate medical attention. A lack of empirical data has led to an absence of reliable recommendations, which tracheal injuries need surgical treatment and in which a conservative approach is to be favored. We present 2 cases of severe traumatic tracheal wall injuries in pediatric patients, a...

Sir, The research articles ‘Exome sequencing reveals mutated SLC19A3 in patients with an early-infantile, lethal encephalopathy’ by Kevelam et al. (2013) and ‘Exome sequencing reveals a novel Moroccan founder mutation in SLC19A3 as a new cause of early-childhood fatal Leigh syndrome’ by Gerards et al. (2013) describe a novel disease entity of an i...

Objectives This retrospective study presents the early and late results of pediatric patients who underwent reconstructive surgery for renovascular hypertension (RVH) between 1979 and 2009. Methods From 1979 to 2009 44 patients (male 22; mean age 13 ± 5.2 years, range 1–19 years; early childhood 7 [1–6 years], middle childhood 5 [7–10 years]; adol...

Zielsetzung: Durch den Einsatz der organspezifischen Dosisreduktion (OSDR) kann die Strahlenexposition oberflachlicher, radiosensitiver Organe (z.B. Schilddruse, Brustparenchym) signifikant reduziert werden. Ziel dieser Studie war es, den Einfluss eines OSDR-Algorithmus auf die Bildqualitat von padiatrischen CT-Thorax-Untersuchungen zu evaluieren....

Background: Organ-specific dose reduction significantly reduces the radiation exposure of radiosensitive organs. Objective: The purpose of this study was to assess the impact of a novel organ-specific dose reduction algorithm on image quality of pediatric chest CT. Materials and methods: We included 28 children (mean age 10.9 ± 4.8 years, rang...

PURPOSE Organ-specific dose reduction (OSDR) algorithms can significantly reduce the radiation exposure to radiosensitive tissues. The purpose of this study was to assess the impact of a novel OSDR algorithm on image quality of pediatric chest computed tomography (CT). METHOD AND MATERIALS Twenty pediatric patients (8 male, 12 female; mean age 12....

Abstract We report on a 16-year-old body builder who suffered from an acute ischemic stroke. In the urine, cannabis metabolites as well as metabolites of the oral androgenic-anabolic steroid methandrostenolone were detected, both known to be associated with stroke events. This report highlights the role of cannabis and steroid abuse that induce str...

Objective: To get insight into the nature of magnetic resonance (MR) white matter abnormalities of patients with classic maple syrup urine disease (MSUD) under diet control. Methods: Ten patients with classic MSUD and one with a severe MSUD variant (mean age 21.5 ± 5.1 years) on diet and 11 age and sex-matched healthy subjects were enrolled. Apa...

Aims/hypothesis: Exercise-induced hyperinsulinism (EIHI) is a hypoglycaemic disorder characterised by inappropriate insulin secretion following anaerobic exercise or pyruvate load. Activating promoter mutations in the MCT1 gene (also known as SCLA16A1), coding for monocarboxylate transporter 1 (MCT1), were shown to associate with EIHI. Recently, t...

Brown-Vialetto-Van Laere syndrome (Online Mendelian Inheritance in Man number 211530) is a neurodegenerative disorder characterized by pontobulbar palsy affecting cranial nerves (mainly VII-XII). Sensorineural deafness is often the leading sign, followed by other neurologic signs. Inheritance is often autosomal recessive, with mutations in the C20o...

Worldwide, only nine cases of revealing slipped capital femoral epiphysis (SCFE) associated with primary hyperparathyroidism (PHP) have been reported. This study included adolescent subjects with the described association, the clinical course, and exhibiting the leading pathogeneses. Here, we reviewed all known cases and developed an effective appr...

We report on a 3.8-year-old girl who was born preterm. Due to a posthemorrhagic hydrocephalus she had a ventriculoperitoneal shunt. Magnetic resonance imaging (MRI) showed mild atrophy of the left cerebellum. She was found unresponsive in a febrile state. After the application of midazolam she regained consciousness. There were no epileptic dischar...

ECG-gated non-enhanced balanced steady-state free precession (bSSFP) MR angiography requires neither breath-holding nor administration of contrast material. To investigate the image quality of free-breathing ECG-gated non-enhanced bSSFP MR angiography of renal arteries in children. Fourteen boys and seven girls (mean age, 9.7 years; range, 7 weeks-...

Chen C, Akanay-Diesel S, Schuster FR, Klee D, Schmidt KG, Donner BC. An unusual manifestation of post-transplant lymphoproliferative disorder in the lip after pediatric heart transplantation. Pediatr Transplantation 2012. © 2012 John Wiley & Sons A/S. Abstract: PTLD is a serious and frequently observed complication after solid organ transplantation...

We report for the first time the impact of neoadjuvant oral low-dose chemotherapy consisting of oral trofosfamide, idarubicin, and etoposide (O-TIE) in the case of alveolar rhabdomyosarcoma (RMS) in the lower jaw of an 18-year-old woman at 27 weeks of gestation, without fetal complications and a highly efficient anti-tumor response. Our study sugge...

Die Kenntnis der Verletzungsmuster bei Kindesmisshandlung schützt das Kind vor einer weiteren Misshandlung und damit vor weiteren auch lebensbedrohlichen Schädigungen der körperlichen Integrität. Neben den klinischen Aspekten müssen durch den Radiologen typische Verletzungsmuster des Skelettsystems, der Organe und der intrakraniellen Strukturen erk...

The implementation of NTBC into treatment of hypertyrosinemia type I (HT I) greatly improved survival by prevention of acute liver failure and hepatocellular carcinoma. However, there are first reports of cognitive impairment in patients with elevated plasma tyrosine concentrations. We here assess the neurocognitive development using standardized p...

We report on a 3.8-year-old girl who was born preterm at 26 weeks of gestation. Due to a posthemorrhagic hydrocephalus she has a ventriculoperitoneal shunt since the age of five months. Clinically she presents with a left-sided spastic hemiparesis. On day of admission she was found unresponsive in a febrile state. After buccal application of midaz...

Psychomotor impairment has been described in hypertyrosinemia types II and III (HT III). Only recently cognitive deficits have also been reported in hypertyrosinemia type I (HT I). The pathogenic mechanisms responsible are unknown. Since implementation of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC, Nitisinone (Swedish Orphan In...

A severe rare complication in patients with branched-chain organic acidurias (BCOA) is pancreatitis with a limited number of patients published so far. Here, we report on a patient with methylmalonic aciduria (MMA) who developed chronic pancreatitis after several episodes of acute pancreatitis. In addition, an overview is given about some previous...

Bloody nipple discharge in adults is, in men as well as in women, often a symptom of an underlying malignant disease. In respect of this, multiple invasive and mutilating diagnostic procedures have been performed in infants and older children. Apart from individual cases in older and pubertal children, in childhood benign conditions are most common...

Ziele: Im Rahmen einer Machbarkeitsstudie zur Etablierung einer max. 10min dauernden MR-Untersuchung des gesamten kindlichen Abdomens wurde neben den statischen Sequenzen T1-Vibe, T2-Haste und DWI eine dynamische TrueFISP-Sequenz zur Evaluation der MR-Durchleuchtung (MR-DL) durchgefuhrt. Wir berichten uber unsere ersten Erfahrungen anhand von 40 Pa...

Ultrasound as the primary prenatal screening modality is used to detect fetal anomalies. Aim of the study was to prove the additional value of fetal magnetic resonance imaging (MRI). In 25 pregnant women (age 30.6 +/- 4.8; 24 single and one twin pregnancy) with pathologic findings of the central nervous system detected by obstetric ultrasound, a fe...

PURPOSE: Ultrasound as the primary prenatal screening modality is used to detect fetal anomalies. Aim of the study was to prove the additional value of fetal magnetic resonance imaging (MRI). MATERIALS AND METHODS: In 25 pregnant women (age 30.6 ± 4.8; 24 single and one twin pregnancy) with pathologic findings of the central nervous system detected...

Glutaric acidemia type II and carnitine palmitoyltransferase type II deficiency are rare, but potentially treatable, inherited metabolic diseases. Hallmarks of the early onset form of both conditions are renal abnormalities and neonatal metabolic crisis. In this article, we report on two newborns with cystic renal dysplasia as a leading sign of the...