Peroxisomal disorders diagnosis

The diagnosis of lysosomal disorders is usually based on enzymatic assays in white blood cells or cultured skin fibroblasts [ 1 ]. Molecular studies required for identification of carriers. Initial diagnosis of peroxisomal disorders... 

Mass spectrometry has become an indispensable method for the analysis of bile acids by virtue of its power to identify, assign structure and quantify free or conjugated bile acids, either pure or in mixtures. It is useful not only to study the metabolism of bile acids but also for the detection and diagnosis of metabolic diseases. Indeed, numerous metabolic diseases resulting from an alteration of the conversion of cholesterol to bile acids have been described, including peroxisomal disorders resulting in a block of (3-oxidation of the lateral chain and other enzyme deficiencies interfering with the biochemistry of the side chain or the steroid nucleus. 

Moser, H., attd Moser, A. (1996). V ry-long-chain fatty acids in diagnosis, pathogenesis, and therapy of peroxisomal disorders. Lipids 31, Si41-Si45. 

D.W. Johnson, M.-U. Trinh, T. Oe, Measurement of plasma pristanic, phytanic and very long chain fatty acids by LC-ESI-MS-MS for the diagnosis of peroxisomal disorders, J. Chromatogr. B, 798 (2003) 159. 

Pineda M, Giros M, Roels F, Espeel M, Ruiz M. Moser A, et al. Diagnosis and follow-up of a case of peroxisomal disorder with peroxisomal mosaicism. J Child Neurol 1999 14(7) 434—439. 

Bile acid CoA esters are the intermediates in the oxidative shortening of the side chain of the C27-bile acids ((3-oxidation) in the biosynthesis of bile acids. Therefore, the blood levels of the bile acid CoA esters and C27-bile acids are good markers for the diagnosis of peroxisomal disorders, such as Zellweger syndrome. The development and clinical applications of the LC-ESl-MS methods for bile acid CoA esters and Cav-bile acids have been reported. 

The primary diagnosis of peroxisomal disorders is made by the GC analysis of very long-chain fatty acids in plasma. Lipids have to be extracted and the analytes have to be derivatized by transesterification [9]. Historically the methyl ester formation was preferred, but alternative derivatives may be more suited for GC/MS analysis [14]. 

Diagnosis of the 4 inborn errors of bile acid synthesis discussed in this chapter is important because three are treatable by oral bile acid supplementation (such treatment was not successful in the single reported case of oxysterol 7a-hydroxylase deficiency). Liquid secondary ion mass spectrometry (LSI-MS) is a simple and rapid method which can be used to screen urine samples for abnormal cholanoids (bile acids and bile alchohols). It should be applied to neonates with unexplained cholestatic liver disease, particularly if familial and associated with steatorrhoea and fat-soluble vitamin malabsorption, to infants and children with developmental delay whether or not this is associated with specific features suggestive of a peroxisomal disorder (e.g. hypotonia, seizures, dysmorphic features, ocular and auditory abnormalities and hepatic dysfunction) or CTX (e.g. juvenile cataracts). 

Johnson, D.W., A rapid screening procedure for the diagnosis of peroxisomal disorders Quantification of very long-chain fatty acids, as dimethylaminoethyl esters, in plasma and blood spots, by electrospray tandem mass spectrometry. J. Inherit. Metab. Dis., 23, 475-486 (2000). 

Fig. 25.6. Flow chart for the differential diagnosis of patients suffering from a peroxisome biogenesis disorder (PBD) or a peroxisomal -oxidation disorder (POD)...

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