133 research outputs found
Managing CLN2 disease: a treatable neurodegenerative condition among other treatable early childhood epilepsies
Get PDFIntroduction : Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is a rare pediatric neurodegenerative condition, which is usually fatal by mid-adolescence. Seizures are one of the most common early symptoms of CLN2 disease, but patients often experience language deficits, movement disorders, and behavioral problems. Diagnosis of CLN2 disease is challenging (particularly when differentiating between early-onset developmental, metabolic, or epileptic syndromes), and diagnostic delays often overlap with rapid disease progression. An enzyme replacement therapy (cerliponase alfa) is now available, adding CLN2 disease to the list of potentially treatable disorders requiring a prompt diagnosis. Areas covered : Although advances in enzymatic activity testing and genetic testing have facilitated diagnoses of CLN2 disease, our review highlights the presenting symptoms that are vital in directing clinicians to perform appropriate tests or seek expert opinion. We also describe common diagnostic challenges and some potential misdiagnoses that may occur during differential diagnosis. Expert opinion : An awareness of CLN2 disease as a potentially treatable disorder and increased understanding of the key presenting symptoms can support selection of appropriate tests and prompt diagnosis. The available enzyme replacement therapy heralds an even greater imperative for early diagnosis, and for clinicians to direct patients to appropriate diagnostic pathways
ASO Author Reflection: Lateral Pelvic Lymph Nodes in Rectal Cancer—Not All Are Created Equal
No full textHidde M. Kroon, Miranda Kusters, and Tarik Sammou
ASO Author Reflection: Isolated Limb Infusion for Locally Advanced Melanoma in the Extremely Old Patient is Safe and Effective
No full textASO Author reflectionsAbstract unavailableJüri Teras, Hidde M. Kroon and Jonathan S. Zage
ASO Author Reflections: Return to Isolated Limb Infusion for In-Transit Melanoma
No full textASO Author ReflectionsMichael J. Carr, Hidde M. Kroon, and Jonathan S. Zage
Mucolipidoses, Multiple Sulfatase Deficiency, and Cathepsin K and C Deficiency
Get PDFMucolipidosis type II/III (ML II/III) and multiple sulfatase deficiency (MSD) share clinical features with the mucopolysaccharidoses. Both ML II/III and MSD result from enzymatic defects that affect the post-translational modification of lysosomal enzymes. In ML II/III the mannose-6-phosphate marker, essential for routing lysosomal enzymes towards the lysosomes, is lacking. This leads to the excretion of lysosomal enzymes in plasma where they are unable to execute their function. In MSD lysosomal sulfatases, as well as sulfatases from the endoplasmic reticulum and Golgi complex, cannot be activated due to the inability to modify a conserved cysteine residue at the active site. In mucolipidosis type IV (ML IV), lysosomal dysfunction is caused by the deficiency of transient receptor potential channel mucolipin-1 (TRPML1), a nonselective cation channel present in late endosomal and lysosomal membranes necessary for autophagy, vesicular trafficking, and mTOR and TFEB signaling. Neurological dysfunction and visual impairment are the most predominant clinical features; skeletal abnormalities are not seen in ML IV. Deficiency of the lysosomal enzymes cathepsin K (pycnodysostosis) and C (Papillon–Lefèvre or Haim–Munk syndrome) presents both with a very distinct clinical picture. Cathepsin K is important for bone resorption and extracellular matrix remodeling. Its deficiency results in stunted growth, facial dysmorphism, osteopetrosis, and dental abnormalities. In cathepsin C deficiency, premature loss of both deciduous and permanent teeth due to periodontitis in combination with palmoplantar keratosis is the main clinical feature.All disorders are ultra-rare and have autosomal recessive inheritance. Their clinical spectrum is not yet fully known, and patients are likely still underdiagnosed. No specific biomarkers are available that can lead to the diagnosis. All disorders have in common that no curative treatments are available and specialized multidisciplinary supportive care is needed to minimize the disease burden and provide an adequate quality of life
OrphanAnesthesia – A common project of the scientific working group of paediatric anaesthesia of the German society of anaesthesiology and intensive care medicine
No full textExtended Abstract: Deficiency of Sodium Taurocholate Cotransporting Polypeptide (SLC10A1): A New Inborn Error of Metabolism with an Attenuated Phenotype
No full textWe present the first patient with a defect in the Na+-taurocholate cotransporting polypeptide SLC10A1 (NTCP), which plays a key role in the enterohepatic circulation of bile salts. The clinical presentation of the child was mild and the child showed no signs of liver dysfunction or pruritus despite extremely elevated plasma bile salt levels (>100-fold upper-limit of normal). A homozygous point mutation was found in the SLC10A1 gene (resulting in amino acid change R252H) and functional studies confirmed the pathogenicity of the mutation. This confirms the role of NTCP as the major transporter of conjugated bile salts into the liver as part of the enterohepatic circulation and shows that other transporters partly can take over its function, resulting in a relatively mild phenotype. This work was published previously in [Vaz et al.: Hepatology 2015;61:260-267] and supplemented with some follow-up information of the patien
ASO Author Reflections: International Experience of Isolated Limb Infusion for Melanoma Shows Durable Response
No full textAbstract unavailableJohn T. Miura, Hidde M. Kroon, and Jonathan S. Zage
MP.2020.2554.Leplaa
No full textBayesian evaluation of replication studies
Author(s) Hidde Jelmer Leplaa, Charlotte Rietbergen, Herbert Hoijtink
Submission to Meta-Psychology. Contains the full history, including all correspondence, decisions, reviews, revisions etc. Anyone can participate in open peer review directly by using the hypothes.is commenting function on the preprint
Inborn Errors of Metabolism
No full textUntil now, most studies on the pathophysiological mechanisms of inborn errors of metabolism have almost exclusively focused on the measurement of concentrations of different metabolites in plasma, urine, or cerebrospinal fluid. These static measurements cannot discriminate between increased or diminished metabolite production and utilization, which limits the interpretation of these studies with respect to the functional consequences of an enzymatic defect. Understanding the changes in dynamics of affected metabolic pathways is a prerequisite for understanding the pathophysiology of a metabolic disorder. Stable isotope infusion techniques have made it possible to study metabolic fluxes in humans in vivo. In this chapter, stable isotope techniques are described to study inborn errors of intermediary glucose, fat, and protein metabolism in vivo
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