Brain MRI and biological diagnosis in five Tunisians MLD patients

Diagnostic Pathology

Abdelhédi Miled³  Salima Ferchichi³  Mahbouba Frih-Ayed¹  Mohamed-Néji Gueddiche²  Hinda Chahed³  Rachida Ben Mansour³  Saber Chebel¹  Samir Hadded²  Ilhem Barboura³ 

[1]Neurological department of CHU Fattouma Bourguiba, Monastir, Tunisia

[2]Pediatric department of CHU Fattouma Bourguiba, Monastir, Tunisia

[3]Laboratory of Biochemistry of CHU Farhat Hached, Sousse, Tunisia

关键词: metachromatic leukodystrophy;    demylinisation;    sulfatide;    urinary sulfatide;    arylsulfatase A;   

Others  :  808159
DOI  :  10.1186/1746-1596-7-11

 received in 2011-09-25, accepted in 2012-01-28,  发布年份 2012

【 摘 要 】

Metachromatic leukodystrophy (MLD) is a recessive autosomal disease which is characterized by an accumulation of sulfatides in the central and peripheral nervous system. It is due to the enzyme deficiency of the sulfatide sulfatase i.e. arylsulfatase A (ASA). we studied 5/200 cases of MLD and clearly distinguished three clinical forms. One of them presented the juvenile form; two presented the late infantile form; and two other presented the adult form. The Magnetic Resonance Imaging (MRI) of these patients showed a diffuse, bilateral and symmetrical demyelination. The biochemical diagnosis of MLD patients evidencing the low activity of ASA and sulfatide accumulation.

Patients and methods

We studied 5/200 MLD patients addressed to us for behavioral abnormalities and progressive mental deterioration. All of them were diagnosed at first by brain MRI evidencing a bilateral demyelination, then the measurement of ASA activity using P-nitrocathecol sulfate as substrate, finally the sulfatiduria was performed using thin-layer chromatography using alpha-naphtol reagent.

Results

In this study, from 200 patients presenting behavioral abnormalities and a progressive mental deterioration, we reported just 2 patients were diagnosed as late-infantile form of MLD. Only1 case presented as the juvenile form; and 2 patients with the adult-type of MLD. The brain magnetic resonance imaging (MRI) of all patients showed characteristic lesions of MLD with extensive demyelination. Biochemical investigations of these patients detected a low level of ASA activity at 0°C and 37°C; the excess of sulfatide in sulfatiduria.

Conclusion

MRI is required to orient the diagnosis of MLD patients; the latter must be confirmed by the biochemical investigations which is based on the measurement of ASA activity and the excess of sulfatide showed in the sulfatiduria.

Virtual Slides

The virtual slide(s) for this article can be found here:

http://www.diagnosticpathology.diagnomx.eu/vs/1791578262610232 webcite

【 授权许可】

   
2012 Barboura et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Von Figura K, Gieselmann V, Jaeken J: Metachromatic leukodystrophy. In The Metabolic and Molecular Bases of Inherited Disease. Edited by Scriver CR, Beaudet AL, Sly WS, Valle D. New York:McGraw-Hill; 2001:3695-3724.
• [2]Önder E, Sinici I, Sönmez FM, Topçu M, Özkara HA: Identification of two novel arylsulfatase A mutation with a polymorphism as a cause of metachromatic leukodystrophy. Neurological Research 2009, 31:60-66.
• [3]Austin JH, Armstrong D, Sheara I, McAfee D: Metachromatic form of diffuse cerebral sclerosis VI. A rapid test for the sulfatase A deficiency in metachromatic leukodystrophy (MLD) urine. Arch Neurol 1966, 14:259.
• [4]Lowry OH, Rosebrough NJ, Farr AL, et al.: Protein measurement with folin phenol reagent. J Biol Chem 1951, 193:265-275.
• [5]Suzuki K: Enzymatic diagnosis of sphingolipidoses. Methods enzymol 1987, 138:727-763.
• [6]Dubois G, Turpin JC, Baumann N: Absence of ASA activity in the healthy father of a metchromatic leukodystrophy (MLD) patient. N Eng J Med 1975, 293:302.
• [7]Jauberteau MO, Ben Younes-Chennoufi A, Rigaud M, Baumann N: IgM gammopathy and polyneuropathy react with an antigenic glycolipid present in human central nervous system. Neurosci Lett 1989, 97:181-184.
• [8]Baumann N, Turpin JC, Lefevre M, Colsh B: Motor and psycho-cognitive clinical types in adult metachromatic leukodystrophy: genotype/phenotype relationship? Journal of physiology 2002, 96:301-306.
• [9]Diez-Roux G, Ballabio A: Sulfatases and human disease. Ann Rev Genomics Hum Genet 2005, 6:355-79.
• [10]Clouter-Mackie MB, Gagnier L: Spectrum of mutations in the arylsulfatase A gene in a Canadian collection including two novel frameshift mutations, a ion (C488R) and an MLD mutation (R84) in cis with a pseudodeficiency allele. Mol Genet Metab 2003, 79:91-8.
• [11]Maire I: Diagnostic prénatal (DPN) des maladies héréditaires du métabolisme (MHM). Biotribune 2004, 12:56-9.
• [12]Polten A, Fluharty AL, Fluharty CB, Kappler J, Von Figura K, Gieselmann V: Molecular basis of different forms of metachromatic leukodystrophy. N Engl J Med 1991, 324:18-22.
• [13]Dali C, Lund AM: thérapie enzymatique substitutive par intraveineuse pour la leukodystrophie metachromatique (MLD). Congrès "Annual Clinical Genetics Meeting", Tampa, Floride (USA), 25-29 mars 2009