Mannose supplementation in PMM2-CDG.

In this response to the letter by Witters et al., we refer to the authors' arguments regarding spontaneous enhancement of glycosylation and the claim, that mannose has no place in the treatment of PMM2-CDG. Our paper "Dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG)" has shown that further investigation of mannose in PMM2-CDG is worthwhile alongside other treatment options and should not be dismissed off-hand without the willingness to prove or disprove it in controlled prospective clinical trials.

Dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG).

Background: PMM2-CDG (CDG-Ia) is the most frequent N-glycosylation disorder. While supplying mannose to PMM2-deficient fibroblasts corrects the altered N-glycosylation in vitro, short term therapeutic approaches with mannose supplementation in PMM2-CDG patients have been unsuccessful. Mannose found no further mention in the design of a potential therapy for PMM2-CDG in the past years, as it applies to be ineffective.

Limitations of galactose therapy in phosphoglucomutase 1 deficiency.

Introduction: Phosphoglucomutase 1 deficiency (PGM1 deficiency) has been identified as both, glycogenosis and congenital disorder of glycosylation (CDG). The phenotype includes hepatopathy, myopathy, oropharyngeal malformations, heart disease and growth retardation. Oral galactose supplementation at a dosage of 1 g per kg body weight per day is regarded as the therapy of choice.

Rapid Diagnosis of 83 Patients with Niemann Pick Type C Disease and Related Cholesterol Transport Disorders by Cholestantriol Screening.

Niemann Pick type C (NP-C) is a rare neurodegenerative disorder caused by an impairment of intracellular lipid transport. Due to the heterogeneous clinical phenotype and the lack of a reliable blood test, diagnosis and therapy are often delayed for years. In the cell, accumulating cholesterol leads to increased formation of oxysterols that can be used as a powerful screening parameter for NP-C.

SLC39A8 Deficiency: A Disorder of Manganese Transport and Glycosylation.

SLC39A8 is a membrane transporter responsible for manganese uptake into the cell. Via whole-exome sequencing, we studied a child that presented with cranial asymmetry, severe infantile spasms with hypsarrhythmia, and dysproportionate dwarfism. Analysis of transferrin glycosylation revealed severe dysglycosylation corresponding to a type II congenital disorder of glycosylation (CDG) and the blood manganese levels were below the detection limit.

It Is Not Always Alcohol Abuse--A Transferrin Variant Impairing the CDT Test.

Aims: Elevated Carbohydrate-deficient transferrin (CDT) levels are used as a biomarker in order to screen for chronic alcohol abuse. Transferrin (Tf) variants can impair methods to measure elevated CDT levels such as high-performance liquid chromatography (HPLC). We present a Tf variant affecting the second glycosylation site of Tf and the complications it causes in diagnosing alcoholism.

News on Clinical Details and Treatment in PGM1-CDG.

Phosphoglucomutase 1 deficiency has recently been reported as a novel disease that belongs to two different classes of metabolic disorders, congenital disorders of glycosylation (CDG) and glycogen storage diseases.This paper focuses on previously reported siblings with short stature, hypothyroidism, increased transaminases, and, in one of them, dilated cardiomyopathy (DCM). An intronic point mutation in the PGM1-gene (c.

Transferrin variants: pitfalls in the diagnostics of Congenital disorders of glycosylation.

Objectives: Transferrin variants can hinder the diagnostic process in cases of suspected Congenital disorders of glycosylation which affect N-Glycosylation. In addition they can impair the use of Carbohydrate deficient Transferrin as a biomarker for chronic alcohol abuse, in which Asialo-Transferrin and Disialo-Transferrin are increased. We present a novel transferrin variant as well as an overview of transferrin mutations found at our laboratory.

The novel transferrin E592A variant impairs the diagnostics of congenital disorders of glycosylation.

Background: The analysis of serum transferrin either by high-performance liquid chromatography (HPLC) or isoelectric focusing (IEF) is the standard diagnostic procedure in patients with the suspicion of a congenital disorder of glycosylation (CDG). Carbohydrate-deficient transferrin (CDT) is also analysed in monitoring programmes in cases of alcohol abuse. We report a novel transferrin variant that impairs the analysis using conventional methods and propose alternative forms of analysis.