SSR4-CDG, an ultra-rare X-linked congenital disorder of glycosylation affecting the TRAP complex: Review of 22 affected individuals including the first adult patient.

Congenital disorders of glycosylation (CDG) are a group of rare, often multi-systemic genetic disorders that result from disturbed protein and lipid glycosylation. SSR4-CDG is an ultra-rare, comparably mild subtype of CDG, presenting mostly in males. It is caused by pathogenic variants in the SSR4 gene, which is located on the X chromosome.

Neurological manifestations in PMM2-congenital disorders of glycosylation (PMM2-CDG): Insights into clinico-radiological characteristics, recommendations for follow-up, and future directions.

Purpose: In the absence of prospective data on neurological symptoms, disease outcome, or guidelines for system specific management in phosphomannomutase 2-congenital disorders of glycosylation (PMM2-CDG), we aimed to collect and review natural history data.

Methods: Fifty-one molecularly confirmed individuals with PMM2-CDG enrolled in the Frontiers of Congenital Disorders of Glycosylation natural history study were reviewed. In addition, we prospectively reviewed a smaller cohort of these individuals with PMM2-CDG on off-label acetazolamide treatment.

Coagulation abnormalities in a prospective cohort of 50 patients with PMM2-congenital disorder of glycosylation.

Background: Given the lack of reliable data on the prevalence of bleeding abnormalities and thrombotic episodes in PMM2-CDG patients, and whether coagulation abnormalities change over time, we prospectively collected and reviewed natural history data. Patients with PMM2-CDG often have abnormal coagulation studies due to glycosylation abnormalities but the frequency of complications resulting from these has not been prospectively studied.

Methods: We studied fifty individuals enrolled in the Frontiers in Congenital Disorders of Glycosylation Consortium (FCDGC) natural history study with molecularly confirmed diagnosis of PMM2-CDG.

Long-term outcomes in ALG13-Congenital Disorder of Glycosylation.

ALG13-CDG is a rare X-linked disorder of N-linked glycosylation. Given the lack of long-term outcome data in ALG13-CDG, we collected natural history data and reviewed individuals surviving to young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature. From the 14 ALG13-CDG patients enrolled into our Frontiers of Congenital Disorders of Glycosylation Consortium natural history study only two patients were older than 16 years; one of these two females is so far unreported.

TRIT1 defect leads to a recognizable phenotype of myoclonic epilepsy, speech delay, strabismus, progressive spasticity, and normal lactate levels.

TRIT1 defect is a rare, autosomal-recessive disorder of transcription, initially described as a condition with developmental delay, myoclonic seizures, and abnormal mitochondrial function. Currently, only 13 patients have been reported. We reviewed the genetic, clinical, and metabolic aspects of the disease in all known patients, including two novel, unrelated TRIT1 cases with abnormalities in oxidative phosphorylation complexes I and IV in fibroblasts.

Nutrition interventions in congenital disorders of glycosylation.

Congenital disorders of glycosylation (CDG) are a group of more than 160 inborn errors of metabolism affecting multiple pathways of protein and lipid glycosylation. Patients present with a wide range of symptoms and therapies are only available for very few subtypes. Specific nutritional treatment options for certain CDG types include oral supplementation of monosaccharide sugars, manganese, uridine, or pyridoxine.

Sorbitol Is a Severity Biomarker for PMM2-CDG with Therapeutic Implications.

Objective: Epalrestat, an aldose reductase inhibitor increases phosphomannomutase (PMM) enzyme activity in a PMM2-congenital disorders of glycosylation (CDG) worm model. Epalrestat also decreases sorbitol level in diabetic neuropathy. We evaluated the genetic, biochemical, and clinical characteristics, including the Nijmegen Progression CDG Rating Scale (NPCRS), urine polyol levels and fibroblast glycoproteomics in patients with PMM2-CDG.

Spontaneous improvement of carbohydrate-deficient transferrin in PMM2-CDG without mannose observed in CDG natural history study.

A recent report on long-term dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG) claimed improved glycosylation and called for double-blind randomized study of the dietary supplement in PMM2-CDG patients. A lack of efficacy of short-term mannose supplementation in multiple prior reports challenge this study's conclusions. Additionally, some CDG types have previously been reported to demonstrate spontaneous improvement in glycosylated biomarkers, including transferrin.

Canines (Canis lupus familiaris) as biodetectors for conservation work: Can they discriminate the rock ptarmigan (Lagopus muta) from the willow grouse (L. lagopus) in a yes/no task?

Alpine and arctic bird populations have shown an unmistakable decrease over the last three decades, and the need for conservation is highly necessary. We investigated the use of five privately-owned dogs (Canis lupus familiaris) as a non-invasive tool to determine the presence of rock ptarmigan (Lagopus muta), through sniffing out faecal pellets, using a yes/no training regime. We carried out 36 double-blind experimental trials per dog and hypothesised that dogs could discriminate the rock ptarmigan from similar species, such as black grouse (Tetrao tetrix), western capercaillie (T.

Scent-sniffing dogs can discriminate between native Eurasian and invasive North American beavers.

The invasion of a species can cause population reduction or extinction of a similar native species due to replacement competition. There is a potential risk that the native Eurasian beaver (Castor fiber) may eventually be competitively excluded by the invasive North American beaver (C. canadensis) from areas where they overlap in Eurasia.

Anatomical variations of the right coronary artery may be a source of difficult block and conduction recurrence in catheter ablation of common-type atrial flutter.

Aims: Although Eustachian valves and recesses have been related to resistance to block, the effect of convective cooling by the right coronary artery (RCA) has not been evaluated in the clinical setting.

Methods And Results: The distance and course of the RCA in relation to the cavotricuspid isthmus (CTI) in addition to variants of CTI anatomy and the presence of Eustachian valves were analysed from computed tomography scans of 54 patients. Ablation power was titrated using a step-up protocol.

Introduction of an expert system for the discrimination of local pulmonary vein and atrial far field signals.

Background: Discrimination of local and far field potentials during sinus rhythm and atrial fibrillation (AF) is essential for successful pulmonary vein (PV) isolation. We sought to introduce an expert system for the classification of electrophysiologic PV signals.

Methods: For the expert system database, we analyzed ablation procedures of 50 patients with paroxysmal and persistent AF.

Slow wall motion rather than electrical conduction delay underlies mechanical dyssynchrony in postinfarction patients with narrow QRS complex.

Introduction: The mechanism of mechanical dyssynchrony in postinfarction patients with a narrow QRS complex is not defined but essential for cardiac resynchronization therapy (CRT).

Methods And Results: Left ventricular electrical activation and subsequent wall motion were recorded for 16 patients with ischemic cardiomyopathy during intrinsic rhythm using a modified NOGA electromechanical mapping system. Ten patients presented mechanical dyssynchrony on tissue Doppler imaging, while 6 patients served as control subjects.

Catheter ablation of multiple ventricular tachycardias after myocardial infarction guided by combined contact and noncontact mapping.

Background: Insights gained from noncontact mapping of ventricular tachycardia (VT) have not been systematically applied to contact maps. This study sought to unify both techniques for an individualized approach to the patient with multiple ischemic VTs irrespective of cycle length.

Methods And Results: For 12 consecutive patients with chronic myocardial infarction and recurrent VT, bipolar contact maps were acquired during sinus or paced rhythm.

Catheter motion during atrial ablation due to the beating heart and respiration: impact on accuracy and spatial referencing in three-dimensional mapping.

Background: The accuracy of three-dimensional mapping systems is affected by cardiac contraction and respiration.

Objective: The study sought to determine relative motion of cardiac and thoracic structures to assess positional errors and guide the choice of an optimized spatial reference.

Methods: Motion of catheters placed at the coronary sinus (CS), pulmonary vein (PV) ostia, left atrial (LA) isthmus and roof, cavotricuspid isthmus (CTI), and right atrial appendage (RAA) were recorded for 30 patients using Ensite-NavX.