Profiles of very-long-chain fatty acids in plasma, fibroblasts, and blood cells in Zellweger syndrome, X-linked adrenoleukodystrophy, and rhizomelic chondrodysplasia punctata

1993 ◽  
Vol 39 (8) ◽  
pp. 1632-1637 ◽  
Author(s):  
R B Schutgens ◽  
I W Bouman ◽  
A A Nijenhuis ◽  
R J Wanders ◽  
M E Frumau
Keyword(s):  
Fatty Acids ◽  
Blood Cells ◽  
Zellweger Syndrome ◽  
Syndrome X ◽  
Chondrodysplasia Punctata ◽  
Long Chain Fatty Acids ◽  
Rhizomelic Chondrodysplasia Punctata ◽  
Peroxisomal Disorders ◽  
Long Chain ◽  
Chain Fatty Acids

Abstract Profiles of saturated very-long-chain (> C22) fatty acids were studied in plasma, fibroblasts, erythrocytes, platelets, and leukocytes of patients affected by peroxisomal disorders such as Zellweger syndrome, X-linked adrenoleukodystrophy (X-ALD), and classic rhizomelic chondrodysplasia punctata (RCDP) and in controls. In Zellweger patients, the concentration of hexacosanoic acid (C26:0) and the C26:0/C22:0 ratio are greatly increased in plasma and fibroblasts. However, the plasma concentration of docosanoic acid (C22:0) is greatly decreased. Also in platelets, leukocytes, and to a lesser extent erythrocytes, the C26:0 concentrations and both the C26:0/C22:0 and C24:0/C22:0 ratios are greatly increased. The C24:0/C22:0 ratio is significantly increased in plasma, platelets, and leukocytes, but not in erythrocytes. In X-ALD, the C26:0 concentration and the C26:0/C22:0 and C24:0/C22:0 ratios are significantly increased in plasma, fibroblasts, platelets, and leukocytes, but the erythrocytes show substantial overlap in the 5-90% ranges between controls and patients. In RCDP, slightly increased C26:0 and C26:0/C22:0 ratios are found in erythrocytes, platelets, and leukocytes, but not in plasma and fibroblasts. We conclude that plasma and fibroblasts are the specimens of choice for biochemical diagnosis of Zellweger syndrome and X-ALD, respectively. The slight increase in C26:0 in blood cells of RCDP patients suggests a decreased flux of very-long-chain fatty acids through the peroxisomal beta-oxidation pathway in liver in this genetic disorder.

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.

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.

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