Neurofilament light chain and glial fibrillary acidic protein levels in metachromatic leukodystrophy.

Metachromatic leukodystrophy is a lethal metabolic leukodystrophy, with emerging treatments for early disease stages. Biomarkers to measure disease activity are required for clinical assessment and treatment follow-up. This retrospective study compared neurofilament light chain and glial fibrillary acidic protein (GFAP) levels in CSF (n = 11) and blood (n = 92) samples of 40 patients with metachromatic leukodystrophy (aged 0-42 years) with 38 neurologically healthy children (aged 0-17 years) and 38 healthy adults (aged 18-45 years), and analysed the associations between these levels with clinical phenotype and disease evolution in untreated and transplanted patients.

Functional analysis of thirty-four suspected pathogenic missense variants in ALDH5A1 gene associated with succinic semialdehyde dehydrogenase deficiency.

Deficiency of succinate semialdehyde dehydrogenase (SSADH; aldehyde dehydrogenase 5a1 (ALDH5A1), OMIM 271980, 610045), the second enzyme of GABA degradation, represents a rare autosomal-recessively inherited disorder which manifests metabolically as gamma-hydroxybutyric aciduria. The neurological phenotype includes intellectual disability, autism spectrum, epilepsy and sleep and behavior disturbances. Approximately 70 variants have been reported in the ALDH5A1 gene, half of them being missense variants.

Guanidinoacetate Methyltransferase Activity in Lymphocytes, for a Fast Diagnosis.

Introduction: Guanidinoacetate methyltransferase (GAMT) deficiency is an inborn error of metabolism (IEM), clinically characterized by intellectual disability, developmental delay, seizures, and movement disorders. Biochemical diagnosis of GAMT deficiency is based on the measurement of creatine and guanidinoacetate in urine, plasma, or CSF and is confirmed genetically by DNA analysis or by enzyme assay in lymphoblasts or fibroblasts. To obtain enough cells, these cells need to be cultured for at least 1 month.

Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects.

Whole-exome sequencing (WES) is increasingly being utilized to diagnose individuals with undiagnosed disorders. Developmental delay and short stature are common clinical indications for WES. We performed WES in three families, using proband-parent trios and two additional affected siblings.

N-acetylaspartate and neurofilaments as biomarkers of axonal damage in patients with progressive forms of multiple sclerosis.

Primary and secondary progressive forms of multiple sclerosis (PPMS and SPMS) have different pathological characteristics. However, it is unknown whether neurodegenerative mechanisms are shared. We measured cerebrospinal fluid (CSF) levels of neurofilament (Nf) light and heavy isoforms and N-acetylaspartic acid (NAA) in 21 PP, 10 SPMS patients and 15 non-inflammatory neurological disease controls (NINDC).

Familial 6p22.2 duplication associates with mild developmental delay and increased SSADH activity.

We present a family with mild developmental delay and a duplication (6)(p22.2). Array CGH analyses revealed this 0.

Quantification of sugar phosphate intermediates of the pentose phosphate pathway by LC-MS/MS: application to two new inherited defects of metabolism.

We describe a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to quantify pentose phosphate pathway intermediates (triose-3-phosphates, tetrose-4-phosphate, pentose-5-phosphate, pentulose-5-phosphates, hexose-6-phosphates and sedoheptulose-7-phosphate (sed-7P)) in bloodspots, fibroblasts and lymphoblasts. Liquid chromatography was performed using an ion pair loaded C(18) HPLC column and detection of the sugar phosphates was carried out by tandem mass spectrometry using an electron ion spray source operating in the negative mode and multiple reaction monitoring. Reference values for the pentose phosphate pathway intermediates in blood spots, fibroblasts and lymphoblasts were established.

Evaluation of pentitol metabolism in mammalian tissues provides new insight into disorders of human sugar metabolism.

To more completely elucidate the pathways of sugar metabolism in human, we have evaluated the formation and degradation of pentitols in human fibroblasts and erythrocytes. Cultured human fibroblasts were incubated with d-arabinose, d-ribose, d-ribulose, and d-xylulose. Formation of arabitol and ribitol was analyzed by gas chromatography of the incubation medium and cell homogenate.

Creatine and guanidinoacetate: diagnostic markers for inborn errors in creatine biosynthesis and transport.

In this study, measurements of guanidinoacetate (GAA) and creatine (Cr) in urine, plasma, and cerebrospinal fluid (CSF) were performed using stable isotope dilution gas chromatography-mass spectrometry. Both compounds were analyzed in a single analysis. Reference values were established for GAA and Cr.

Disease-related metabolites in culture medium of fibroblasts from patients with D-2-hydroxyglutaric aciduria, L-2-hydroxyglutaric aciduria, and combined D/L-2-hydroxyglutaric aciduria.

Background: D-2-Hydroxyglutaric aciduria (D-2-HGA), L-2-hydroxyglutaric aciduria (L-2-HGA), and the combined D/L-2-hydroxyglutaric aciduria (D/L-2-HGA) are poorly understood organic acidurias. To investigate the usefulness of cultured human skin fibroblasts for both diagnostic and research purposes, we measured disease-related metabolites in the cell culture medium.

Methods: We measured D-2-hydroxyglutarate (D-2-HG), L-2-hydroxyglutarate (L-2-HG), succinate, 2-ketoglutarate, and citrate in fibroblast cell medium by stable-isotope-dilution gas chromatography-mass spectrometry and glutamine, glutamic acid, and lysine with an amino acid analyzer.