scholarly journals Advanced Diagnostic System and Introduction of Newborn Screening of Adrenoleukodystrophy and Peroxisomal Disorders in Japan

2021 ◽  
Vol 7 (3) ◽  
pp. 58
Author(s):  
Nobuyuki Shimozawa ◽  
Shigeo Takashima ◽  
Hiroki Kawai ◽  
Kazuo Kubota ◽  
Hideo Sasai ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Early Stage ◽  
Diagnostic System ◽  
Rapid Diagnosis ◽  
Long Chain Fatty Acids ◽  
Peroxisomal Disorders ◽  
Hematopoietic Stem ◽  
Molecular Analyses ◽  
Long Chain ◽  
Screening Approaches

We established a diagnostic system for adrenoleukodystrophy (ALD) and peroxisomal disorders (PD) over 35 years ago in Japan, and have diagnosed 237 families with ALD and more than 100 cases of PD other than ALD using biochemical and molecular analyses. In particular, since the only treatment for the cerebral form of ALD is hematopoietic stem cell transplantation at an early stage of onset, we have developed a protocol for the rapid diagnosis of ALD that can provide the measurements of the levels of very-long-chain fatty acids in the serum and genetic analysis within a few days. In addition, to improve the prognosis of patients with ALD, we are working on the detection of pre-symptomatic patients by familial analysis from the proband, and the introduction of newborn screening. In this review, we introduce the diagnostic and newborn screening approaches for ALD and PD in Japan.

Fit-for-purpose biomarker LC–MS/MS qualification for the quantitation of very long chain fatty acids in human cerebrospinal fluid

Bioanalysis ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 143-158
Author(s):  
John Williams ◽  
Kan Zhu ◽  
Eric Crampon ◽  
André Iffland
Keyword(s):  
Fatty Acids ◽  
Cerebrospinal Fluid ◽  
Specific Binding ◽  
Long Chain Fatty Acids ◽  
Absolute Quantitation ◽  
Peroxisomal Disorders ◽  
Healthy Human ◽  
Fit For Purpose ◽  
Long Chain ◽  
Chain Fatty Acids

Aim: Very long chain fatty acids (VLCFAs) have been identified as biomarkers for several peroxisomal disorders necessitating the need for reliable biomarker assays in particular C20, C22, C24, C26 in cerebrospinal fluid (CSF). Until now no absolute quantitation assay for total VLCFAs in CSF has been successfully developed and qualified for clinical use. Methodology: A quantitative LC–MS/MS assay for total VLCFA in human CSF was developed. Derivatization tag and coupling chemistry were optimized for sensitivity. CSF contamination by blood, non-specific binding of VLCFA to surfaces and exogenous VLCFA contamination was minimized. Discussion/conclusion: This fit for purpose biomarker assay was used to measure baseline healthy human VLCFA levels across multiple subjects to establish an understanding of concentration ranges and feasibility.

Ratios for very-long-chain fatty acids in plasma of subjects with peroxisomal disorders, as determined by HPLC and validated by gas chromatography-mass spectrometry.

1988 ◽  
Vol 34 (6) ◽  
pp. 1041-1045 ◽  
Author(s):  
N A Hall ◽  
G W Lynes ◽  
N M Hjelm
Keyword(s):  
Fatty Acids ◽  
Zellweger Syndrome ◽  
Hplc Method ◽  
Gas Chromatography Mass Spectrometry ◽  
Long Chain Fatty Acids ◽  
Peroxisomal Disorders ◽  
One Year ◽  
Derivatives Of ◽  
Long Chain ◽  
Chain Fatty Acids

Abstract We describe an HPLC method for measurement of ratios of concentrations of very-long-chain fatty acids (VLCFA) in plasma. The method, which involves ultraviolet detection of p-bromophenacyl derivatives of fatty acids, is validated by comparison with a gas chromatographic-mass spectrometric (GC-MS) method. The correlation between the ratios of 24-carbon fatty acids to 22-carbon fatty acids (C24/C22) estimated by the two methods was close (r = 0.976) as was the correlation for the C26/C22 ratios (r = 0.947). Increased VLCFA ratios could be demonstrated by either technique in patients with adrenoleukodystrophy, Zellweger syndrome, and infantile Refsum's disease. The HPLC method also measures phytanate concentrations in plasma. Control VLCFA ratios (for subjects without peroxisomal disorders) obtained by the two methods agree well with those reported by Moser et al. (Ann Neurol 1984; 16:628-41). For subjects younger than one year, ratios for C24/C22 and C26/C22 fatty acids were significantly greater than in older subjects.

Peroxisomal Disorders: Experience from a Genetic Center in North India

2018 ◽  
Vol 17 (02) ◽  
pp. 065-070
Author(s):  
Suresh Kumar Angurana ◽  
Renu Suthar ◽  
Inusha Panigrahi
Keyword(s):  
Fatty Acids ◽  
North India ◽  
Chondrodysplasia Punctata ◽  
Long Chain Fatty Acids ◽  
Rhizomelic Chondrodysplasia Punctata ◽  
Peroxisomal Disorders ◽  
Clinical Profiles ◽  
Characteristic Features ◽  
Biochemical Features ◽  
Long Chain

AbstractDiagnosis of peroxisomal disorders (PDs) is often delayed because of unfamiliarity with the characteristic features of PDs and their genetic heterogeneity. Aim of this study was to describe clinical profiles of six children with PDs. This is a retrospective study involving six children with PDs. The patients included three males, one female, and a fetus. Three patients were diagnosed with Zellweger's syndrome, two with rhizomelic chondrodysplasia punctata, and one with X-linked adrenoleukodystrophy. These diagnoses were established based on clinical, radiological, and biochemical features (elevated very long chain fatty acids levels). Parents of all cases have been provided genetic counseling and advised of prenatal diagnosis. Diagnosis of PDs requires knowledge of characteristic clinicoradiological features, and clinical confirmation is possible with simple imaging and biochemical investigations. Molecular diagnosis is possible for selected cases.

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