Gallbladder polyposis in metachromatic leukodystrophy

Gallbladder polyposis is a rare entity that can be associated with conditions such as metachromatic leukodystrophy (MLD), but the literature is sparse. We present a child with gallbladder polyposis who was diagnosed with MLD 15 months later despite normal neuroimaging and clinical examination initially.     

Unusual gallbladder findings in two brothers with metachromatic leukodystrophy

Characteristic biliary tree abnormalities in metachromatic leukodystrophy (MLD) include gallbladder polyposis and haemobilia. We report two brothers with MLD, who presented with uncommon biliary complications. One presented with gastric outlet obstruction secondary to gallbladder enlargement, which was treated by percutaneous aspiration. He later developed gallbladder carcinoma with liver metastases. His brother demonstrated US findings consistent with gallstones. Received: 20 August 1997 Accepted: 23 February 1998     

Chronic hemorrhagic pancreatitis in gallbladder polyposis as an initial symptom of metachromatic leukodystrophy

A 4 1/2 year old boy without previous neurologic disorders developed chronic hemorrhagic pancreatitis and was shown to have polyposis of the gallbladder. Neurologic symptoms emerged at the age of 5 years. The sonographic pattern of an echogenic gallbladder was suspect of metachromatic leukodystrophy. The definitive diagnosis was made by the findings of very low arylsulfatase A activity in the white blood cells and deposits of sulfatides in the stroma of the polyps of the gallbladder.     

Papillomatous Transformation of the Gallbladder in Metachromatic Leukodystrophy

Papillomatous transformation of the gallbladder was found in a patient with metachromatic leukodystrophy who presented with an abdominal mass. Cholecystectomy was performed, and involvement of the gallbladder was confirmed by metachromatic stains and electron microscopy.     

Papillomatous transformation of the gallbladder in metachromatic leukodystrophy

Papillomatous transformation of the gallbladder was found in a patient with metachromatic leukodystrophy who presented with an abdominal mass. Cholecystectomy was performed, and involvement of the gallbladder was confirmed by metachromatic stains and electron microscopy.     

Papillomatosis of the gallbladder in metachromatic leukodystrophy

A 2-year-old boy who presented with a cystic gallbladder mass was found histologically to have metachromatic leukodystrophy. Diffuse hyperplasia of the gallbladder mucosa, multiple tendrillar fronds extending into the lumen, extensive papillomatosis, and the presence of large numbers of macrophages bearing metachromatic material confirmed the diagnosis. The child developed progressive degeneration of the central nervous system, refractory bronchopneumonia, and generalized muscular atrophy. A computed tomographic scan of the brain demonstrated hypodense areas of white matter suggestive of demyelination. This report describes the rare association of gallbladder papillomatosis with a storage disorder and reviews the relevant literature.     

Immunologic studies of arylsulfatase A in normal and metachromatic leukodystrophy liver.

Purified human liver arylsulfatase A on polyacrylamide gel electrophoresis at pH 4.0 is separated into two protein forms with enzymatic activity and two distinct inactive subunits. All of these components were immunologically distinguishable using different antisera preparations. In late infantile metachromatic leukodystrophy, only one of the two inactive subunits was immunologically detected, whereas in the juvenile form of metachromatic leukodystrophy, both inactive subunits were antigenically present.     

Siblings with the Austin variant of metachromatic leukodystrophy multiple sulfatidosis

Siblings with multiple sulfatase deficiency, a rare variant of metachromatic leukodystrophy are described. The diagnosis was based on clinical findings and confirmed by leukocyte enzymes estimation, tissue histopathology and histochemistry. The condition is briefly reviewed, and its hall-mark-the combination of features of metachromatic leukodystrophy (MLD) and mucopolysaccharidosis (MPS) are highlighted.     

Prenatal metachromatic leukodystrophy.

In a family with a metachromatic leukodystrophy patient, two further pregnancies at risk were monitored by amnion cell culture. In one case, a normal baby was predicted and born. In the other case, a prenatal deficiency of arylsulfatase A was found. The diagnosis of metachromatic leukodystrophy was confirmed biochemically in various organs of the fetus by the deficiency of arylsulfatase A. The residual enzyme activity was shown to have an abnormal pH optimum and an increased heat stability. Ultrastructural studies revealed lipid storage in the myelinating nervous system and in the liver. For the interpretation of morphological results, it was indispensable to analyze an age-matched control fetus.     

Arylsulfatase A pseudodeficiency incidence in Turkey

Pseudodeficiency (Pd) in arylsulfatase A (ASA) is a relatively frequent condition in healthy individuals. It produces a reduction in enzyme activity similar to that found in metachromatic leukodystrophy (MLD). A variable incidence of the Pd allele was found in different populations; it was 10-20 times higher than that of metachromatic leukodystrophy. Twelve of the 52 unrelated, healthy individuals were found to be heterozygous for the ASA Pd allele. In Turkey we estimated the incidence of the Pd allele as 11.5 percent. Out of 18 cases with MLD, one patient was found homozygous for the Pd allele and the other patient was found heterozygous.     

Proximal renal tubular acidosis in metachromatic leukodystrophy.

A 2-year-old girl affected with the late infantile form of metachromatic leukodystrophy had a persistent and moderate metabolic acidosis. Renal functional studies demonstrated the presence of decreased tubular reabsorption of sodium, bicarbonate and some amino acids. Other tubular functions, including distal urinary acidification and concentrating mechanism were normal. Glomerular filtration rate was moderately decreased. Metachromatic inclusions were demonstrated along the nephron by histochemistry and electron microscopy. Tubular dysfunction in metachromatic leukodystrophy could have been overlooked until now given the severity of the neurological picture.     

小儿脑白质营养不良的临床诊断问题———附38例临床分析

目的对３８例脑白质营养不良患儿进行分析，探讨其诊断问题。方法采用临床检查与生化检查综合分析，同时探讨影像学和实验室检查与临床的关系。结果６例诊断为异染性脑白质营养不良（ｍｅｔａｃｈｒｏｍａｔｉｃｌｅｕｋｏｄｙｓｔｒｏｐｈｙ，ＭＬＤ），１３例诊断为肾上腺脑白质营养不良（ａｄｒｅｎｏｌｅｕｋｏｄｙｓｔｒｏｐｈｙ，ＡＬＤ），２例为先天性皮质外轴索再生障碍症（Ｐｅｌｉｚａｅｕｓ－Ｍｅｒｚｂａｃｈｅｒｄｉｓｅａｓｅ，ＰＭＤ），余１７例病因未明确。文中对几种脑白质营养不良的早期诊断作出分析，同时分析了影像学诊断和实验室检查与临床间的关系，讨论了脑白质营养不良近年的研究进展。结论加强随访工作和遗传咨询，同时进一步做临床基因诊断，对脑白质营养不良的诊断和治疗具有重要作用     

Metachromatic leukodystrophy: consequences of sulphatide accumulation

Metachromatic leukodystrophy is a lysosomal lipid storage disorder. It is caused by mutations in the gene for arylsulphatase A, an enzyme involved in the degradation of the sphingolipid 3'-O-sulphogalactosylceramide (sulphatide). This membrane lipid can be found in various cell types, but in particularly high concentrations in the myelin of the nervous system. Patients suffer from progressive, finally lethal, demyelination due to accumulation of sulphatide. In the nervous system, lipid storage not only affects oligodendrocytes but also neurons and, in addition, leads to astrogliosis and activation of microglia. At the cellular level, lysosomal sulphatide storage also affects the lipid composition of myelin itself and has consequences for the amount and localization of particular myelin membrane-associated proteins. Here we review data, largely based on an arylsulphatase A knock-out mouse model of metachromatic leukodystrophy.
Conclusion : The knock-out mouse model of metachromatic leukodystrophy has provided insights into the histopathological and cellular consequences of sulphatide storage.     

Metachromatic leukodystrophy: consequences of sulphatide accumulation

Metachromatic leukodystrophy is a lysosomal lipid storage disorder. It is caused by mutations in the gene for arylsulphatase A, an enzyme involved in the degradation of the sphingolipid 3'-O-sulphogalactosylceramide (sulphatide). This membrane lipid can be found in various cell types, but in particularly high concentrations in the myelin of the nervous system. Patients suffer from progressive, finally lethal, demyelination due to accumulation of sulphatide. In the nervous system, lipid storage not only affects oligodendrocytes but also neurons and, in addition, leads to astrogliosis and activation of microglia. At the cellular level, lysosomal sulphatide storage also affects the lipid composition of myelin itself and has consequences for the amount and localization of particular myelin membrane-associated proteins. Here we review data, largely based on an arylsulphatase A knock-out mouse model of metachromatic leukodystrophy. CONCLUSION: The knock-out mouse model of metachromatic leukodystrophy has provided insights into the histopathological and cellular consequences of sulphatide storage.     

Ultrastructural study of peripheral lymphocytes and polymorphonuclear leukocytes in children with lysosomal enzymopathies and hyperlipoproteinemia

On the basis of electronmicroscopic examinations of the peripheral lymphocytes and polymorphonuclear leukocytes (PMNL) in mucopolysaccharidosis of types I and II in Gaucher and Nieman-Pick diseases, in metachromatic leukodystrophy and in hyperlipoproteinemia, the ultrastructural characteristics are described. Pathological findings with vacuoles formations were observed in Gaucher disease and in metachromatic leukodystrophy against the preliminary literature. The ultrastructural pathological changes are reported from the first ultrastructural PMNL examinations in hyperlipoproteinemias. Electronmicroscopic analysis of the leukocytes is considered to give information equivalent in value to that from liver biopsy studies, but is advantageous in view of its non-invasive nature.     

Bone marrow transplantation for late infantile metachromatic leukodystrophy: Pathogenic investigation for graft rejection

A Japanese boy aged 2 years 11 months with late infantile metachromatic leukodystrophy underwent bone marrow transplantation (BMT) from his human leukocyte antigen (HLA) identical but mixed lymphocyte culture reactive father. Chimerism and increased arylsulfatase A activities of leukocytes had been observed with retarded progression of neurological deterioration during the first 3 months post-BMT. Graft rejection gradually occurred and donor cells were almost completely eliminated from the patient at 1 year after BMT. The process of neurodegeneration progressed clinically and neuroradiologically. Three possible reasons for the pathogenesis of graft rejection are: (i) T cell depletion of donor marrow cells as graft-versus-host disease (GVHD) prophylaxis; (ii) a slightly weak conditioning regimen; and (iii) a small number of marrow cells transplanted. It is stressed that as BMT is still a preliminary therapy for metachromatic leukodystrophy indications, conditioning, and GVHD prophylaxis for BMT should be considered individually.     

Biliary disease in metachromatic leukodystrophy

Pediatric Radiology - This paper illustrates the previously unreported sonographic changes in the biliary tract in metachromatic leukodystrophy (MLD). Gallbladder wall thickening due to sulfatide...     

Diagnosis of pseudo-arylsulfatase A deficiency with electrophoretic techniques

Deficient arylsulfatase A activity in man has long been associated with the neurodegenerative disease, metachromatic leukodystrophy. However, similar deficiency has been noted in clinically normal individuals, and is referred to as the pseudoarylsulfatase A deficiency condition. Although direct quantitative analysis of arylsulfatase A activity failed to differentiate between these two conditions, analysis of residual arylsulfatase A activity with either Cellogel electrophoresis or isoelectric focusing in polyacrylamide gels now has been shown to distinguish between them unequivocally. With both techniques, cultured fibroblasts from patients with pseudo-arylsulfatase A deficiency showed faint but clear bands of arylsulfatase A activity. Under identical conditions, fibroblasts from patients with metachromatic leukodystrophy showed no trace of activity. These methods can be adapted easily for general laboratory analysis in cases when results from quantitative arylsulfatase A assays are noninformative.     

Spontaneous rupture of the diaphragm.

A 2.5 year old girl with metachromatic leukodystrophy presented with acute respiratory distress and was initially wrongly diagnosed with pneumothorax. Barium meal showed bowel loops in the left hemithorax, which prompted surgical intervention; spontaneous rupture of the diaphragm was diagnosed at surgery.     

Spontaneous rupture of the diaphragm

A 2.5 year old girl with metachromatic leukodystrophy presented with acute respiratory distress and was initially wrongly diagnosed with pneumothorax. Barium meal showed bowel loops in the left hemithorax, which prompted surgical intervention; spontaneous rupture of the diaphragm was diagnosed at surgery.