Metachromatism

Mastocytosis is recognized in most patients because of the presence of characteristic cutaneous lesions [10]. A positive Darier s sign and/or histological examination of the skin using metachromatic stains, or by immunohistochemistry using antibodies to mast cell tryptase, helps confirm the diagnosis of cutaneous disease. 

Metachromatic ieukodystrophy Aryisuifatase A Cgp—Gsl—j-OS03 3-Sulfogalactosylceramide Mental retardation and psychologic disturbances in adults demyelination. 

The property of polyanions to give metachromatic reactions with basic dyes80 (see Section XI) has been widely exploited for the titration of glycosaminoglycans. Because of its high charge-density, heparin displays large shifts in the visible spectrum of the dye upon complex-formation, and can conveniently be titrated (most commonly, with Methylene Blue or Azure A), even in the presence of minor proportions of other glycosaminoglycans. It should be realized that quantitative responses with metachromatic dyes are different for different pure heparin... 

On the other hand, Widra found metachromatic granules to contain protein-bound lipide, RNA, and polyphosphates. 

Using specific fluorescent transport substrates, inhibitors and kinetic analysis Using fluorescent xenobiotics or fluorescent analogue of xenobiotics Using special fluorescent xenobiotics or fluorescent analogues of xenobiotics Vital tests with acridine orange or neutral red Metachromatic fluorescence of intercalated or bound acridine orange, 590/530 nm microfluorometry... 

Neuropathies can result from mutations that alter the structure or level of expression of PNS myelin proteins (e.g. overexpression of PMP22 in Charcot-Marie-Tooth syndrome (CMT) type 1A), the metabolism of myelin lipids (e.g. metachromatic leukodystrophy), or the capacity of PNS neurons to support their axons in patients with CMT caused by mutations of KIF1B [4] or NF-L [5, 6]. Both acquired and inherited amyloid neuropathies can result from the deposition of poorly soluble proteins, for example cryoglobulins or mutant transthyretins, in and around endoneurial bloodvessels [7-9]. 

Familial demyelinative/dysmyelinative and axonal neuropathies may also be caused by impaired lysosomal lipid metabolism. Metachromatic leukodystrophy (sulfatide lipidosis) results from mutations of the arylsulfatase A gene, which encodes a lysosomal enzyme required for sulfatide turnover. Myelin is affected in both CNS and PNS, though dysfunction is restricted to the PNS in some patients, and the onset of symptoms can occur at any time between infancy and adulthood. Bone marrow transplantation can slow disease progression and improve nerve conduction velocities [57]. (See in Ch. 41.)... 

Gieselmann, V., Matzner, U., Hess, B. et al. Metachromatic leukodystrophy molecular genetics and an animal model. /. Inherit. Metab. Dis. 21 564-574,1998. 

Metachromatic leukodystrophy AR Aryl sulfatase A Accumulation of sulfatide in brain see text 1,2, Ch. 40... 

Metachromatic leukodystrophy is due to a defect in arylsulfatase A (ASA). There are three major forms late infantile, juvenile and adult. The overall incidence is 1 40,000. In the late infantile and early juvenile forms, which comprise about 80% of patients, the initial symptoms involve the motor system, with falls, loss of ability to walk, flaccid paralysis, difficulty in swallowing, loss of speech, vision, seizures, decerebrate state and death 1-7 years after onset of symptoms. In the adolescent and... 

Globoid leukodystrophy Metachromatic leukodystrophy X-linked adrenoleukodystrophy Refsum s disease Cystinosis... 

Otsuka H, Mezawa A, Ohnishi M, Okubo K, Seld H, Okuda M Changes in nasal metachromatic cells during allergen immunotherapy. Clin Exp Allergy 1991 21 115-119. 

Very rare disorders include juvenile metachromatic leukodystrophy, adrenoleucodystrophy, Wilson s disease These conditions are associated with movement disorders, particularly gait disturbance. It is important to attempt to distinguish between primary and secondary (antipsychotic related) movement disorders These conditions are characterized by a progressive loss of cognitive skills (in contrast to the more relative decline seen in schizophrenia and other developmental disorders, where a loss of previously learned skill is unusual)... 

Iversen SD 5-HT and anxiety. Neuropharmacology 23 156-164, 1984 Iwamori M, Moser HW, Kishimoto Y Steroid sulfatase in brain comparison of sulfohydrolase activities for various steroid sulfates in normal and pathological brains, including various forms of metachromatic leukodystrophy. J Neurochem 27 1389-1395, 1976... 

In case of a deficiency of arylsulfatase A, at least one other sulfatase should be measured to exclude multiple sulfatase deficiency (see Chap. 4.1 for the assays of arylsulfatase and other sulfatases). Sulfatide excretion in urine should be measured (see assay below) and/or mutation analysis should to performed to confirm the diagnosis, especially if the clinical symptoms are atypical and in order to exclude a pseudodeficiency of arylsulfatase A. The enzyme should always be measured in the parents to check for the presence of compound heterozygosity of a metachromatic leukodystrophy and a pseudodeficiency allele. This is very important for the interpretation of the results of arylsulfatase A assays, especially when performed in asymptomatic or presymptomatic siblings or in the context of a prenatal diagnosis. Sulfatide should also be measured in case a normal arylsulfatase A activity is found in a patient with symptoms characteristic of (juvenile) metachromatic leukodystrophy. Increased urinary sulfatide excretion is indicative of an activator protein/saposin deficiency (Fig. 4.4.1). 

Natowicz MR, Prence EM, Chaturvedi P, Newburg DS (1996) Urinary sulfatides and the diagnosis of metachromatic leukodystrophy. Clin Chem 42 232-238... 

Rafi MA, Coppola S, Liu SL, Rao HZ, Wenger DA (2003) Disease-causing mutations in cis with the common arylsulfatase A pseudodeficiency allele compound the difficulties in accurately identifying patients and carriers of metachromatic leukodystrophy. Mol Genet Metab 79 83-90... 

Whitfield PD, Sharp PC, Johnson DW, Nelson P, Meikle PJ (2001) Characterization of urinary sulfatides in metachromatic leukodystrophy using electrospray ionization-tandem mass spectrometry. Mol Genet Metab 73 30-37... 

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