Clinical, biochemical and genetic characteristics of MOGS-CDG: a rare congenital disorder of glycosylation.

Purpose: To summarise the clinical, molecular and biochemical phenotype of mannosyl-oligosaccharide glucosidase-related congenital disorders of glycosylation (MOGS-CDG), which presents with variable clinical manifestations, and to analyse which clinical biochemical assay consistently supports diagnosis in individuals with bi-allelic variants in .

Methods: Phenotypic characterisation was performed through an international and multicentre collaboration. Genetic testing was done by exome sequencing and targeted arrays.

The critical role of psychosine in screening, diagnosis, and monitoring of Krabbe disease.

Purpose: Newborn screening (NBS) for Krabbe disease (KD) is performed by measurement of galactocerebrosidase (GALC) activity as the primary test. This revealed that GALC activity has poor specificity for KD. Psychosine (PSY) was proposed as a disease marker useful to reduce the false positive rate for NBS and for disease monitoring.

Urine oligosaccharide screening by MALDI-TOF for the identification of NGLY1 deficiency.

N-glycanase deficiency (NGLY1 deficiency, NGLY1-CDDG), the first autosomal recessive congenital disorder of N-linked deglycosylation (CDDG), is caused by pathogenic variants in NGLY1. The majority of affected individuals have been identified using exome or genome sequencing. To date, no reliable, clinically available biomarkers have been identified.

Prospective differentiation of multiple system atrophy from Parkinson disease, with and without autonomic failure.

Objective: To report preliminary results of a prospective ongoing study of multiple system atrophy (MSA) and Parkinson disease (PD), with a large subset of patients with PD with autonomic failure (25%), to evaluate autonomic indices that distinguish MSA from PD.

Methods: We used consensus criteria, detailed autonomic studies (Composite Autonomic Symptom Scale, Composite Autonomic Scoring Scale, thermoregulatory sweat test, and plasma catecholamines), and functional scales (Unified MSA Rating Scale [UMSARS] I-IV and Hoehn-Yahr grading) on a prospective, repeated, and ongoing basis.

Results: We report the results of a study on 52 patients with MSA (mean [SD], age, 61.

Acetylcholinesterase inhibition in patients with orthostatic intolerance.

The efficacy of current therapeutic measures in orthostatic intolerance (OI) varies among patients and is oftentimes unsatisfactory. New approaches to alleviate symptoms of OI are therefore clearly needed. Recent reports have demonstrated that acetylcholinesterase inhibition is effective in the treatment of orthostatic hypotension with the presumed mechanism of enhancing sympathetic ganglionic transmission.

Stability of acetylcholine chloride solution in autonomic testing.

Acetylcholine (ACh) is the neurotransmitter used as an agent to evoke a sudomotor axon reflex response in autonomic testing. Adequate stimulus of postganglionic axons requires ACh solutions to be stable, but its stability in the clinical laboratory is uncertain. We evaluated the stability of standard (0.

A screen of candidate genes and influence of beta2-adrenergic receptor genotypes in postural tachycardia syndrome.

Objective: To screen candidate genes, encoding beta2-adrenergic receptor (beta2AR), alpha2C-adrenergic receptor (alpha(2C)AR), norepinephrine transporter (NET), and mitochondrial complex I (COI), for common single nucleotide polymorphisms (SNPs) in patients with postural tachycardia syndrome (POTS); alterations could potentially cause or aggravate orthostatic tachycardia and to relate beta2AR SNPs, known to effect venomotor tone, to heart rate (HR) and blood pressure measurements during 10-min head-up tilt.

Methods: (a) DNA extraction from leukocytes of 29 patients with POTS; (b) Denaturing high performance liquid chromatography analysis to screen for the 12-bp deletion (Del322-325) in alpha(2C)AR and for the alanine to proline mutation at amino acid 457 (Ala457Pro) in NET; (c) Systematic direct sequence analysis to screen for SNPs in beta2AR, NET, and COI.

Results: Three common polymorphisms were abundant in at least one allele in beta2AR resulting in a cysteine to arginine in the 5' promoter region (72% of patients), an arginine to glycine at amino acid-16 (Gly16; 86%), and a glutamine to glutamic acid at amino acid-27 (Glu27; 66%), a frequency that was no different to the normal Caucasian population.

Assessment of the "common" 4.8-kb mitochondrial DNA deletion and identification of several closely related deletions in the dorsal root ganglion of aging and streptozotocin rats.

The identification of several mitochondrial DNA (mtDNA) deletions and the accumulation of the "common" 4.8-kb mitochondrial DNA deletion (mtDNA(4834)) with aging and experimental streptozotocin-induced diabetes (STZ) were studied in the rat dorsal root ganglion (DRG). Twenty-one mtDNA deletions, including mtDNA(4834), were identified in rat L4-L6 DRG mtDNA of 15-month-old Spraque-Dawley rats with 13 months of STZ and age-matched controls.