An adult case of metachromatic leukodystrophy

The findings are described in an adult case of metachromatic leukodystrophy examined by light, polarization and electron microscopy. Symmetrical demyelination was found in the cerebral hemispheres, but was moderate in the cerebellum, brain stem and spinal cord. Early changes in myelin of peripheral nerves have been demonstrated by polarization microscopy. Various metachromatic structures have been described in glial cells and neurons by electron microscopy, indicating disturbances at different metabolic steps of lipid metabolism. There are minor but no essential ultrastructural differences in the disease of different ages.     

An adult onset metachromatic leukodystrophy with dominant inheritance and normal arylsulphatase A levels

A family with a variant of adult onset metachromatic leukodystrophy is presented. Clinical details from three affected members are given. The neurophysiological and neuroradiological data on the two brothers who have been recently studied are included. One of these died and the post-mortem findings are discussed along with those from a cousin who died some years ago. Arylsulphatase A levels were normal in both brothers yet the histological findings in the one who died are of a metachromatic leukodystrophy and thin-layer chromatography confirms an excess of sulphatides in the white matter of his brain. Disabling hypotension was a striking feature in both brothers but adrenal function was shown to be intact and autonomic neuropathy seemed the likely cause. Study of the family suggests a dominant mode of inheritance.     

Variable onset of metachromatic leukodystrophy in a Vietnamese family

We report two siblings with metachromatic leukodystrophy, one who presented at 7 years of age (juvenile onset) and his sister who presented at 22 years of age (adult onset). They are compound heterozygotes for two novel mutations in the arylsufatase A gene (ARSA). The responsible mutations in this Vietnamese family consist of a missense mutation with 5% enzyme activity (R143G) and a nonsense mutation (W318ter), from which no enzyme activity would be expected. These mutations in the ARSA gene have not been previously reported and may be useful when diagnosing metachromatic leukodystrophy in other affected Vietnamese individuals. The variability in presentation suggests that the genotype alone is not sufficient to determine the onset and course of the disease and modifying genetic and perhaps nongenetic factors likely contribute.     

Later onset metachromatic leukodystrophy diagnosed by nerve biopsy]

Three cases of later onset metachromatic leukodystrophy in one family were reported. The brother is 32 years old, younger sister is 35 years old and the elder sister is 39 years old, who were normal as child without any family history of neurological disease. The three cases began their illness at about the age of 30 years old with dysarthria, progressive dementia, motor disturbance and numbness in the extremities. CT scan showed low density in the white matter of frontal, parietal lobes and around the ventricle. The written reports of CT scan were lacunar infarction in brother, multiple lacunar infarction in younger sister and Binswanger's disease in elder sister. Nerve biopsy showed myelinated fibers were decreased in number. Metachromatical materials were seen in and around the Schwann cell cytoplasm. Metachromatical materials were lamillar inclusions in granular matrix by electromicroscopic examination. So nerve biopsy is easy, safe and effective method to diagnose the uncertain pathogenic leukoence-phalopathy.     

Neuropathological and enzymatic studies in a case of adult form of metachromatic leukodystrophy with very late onset of clinical symptoms

Metachromatic leukodystrophy is a genetical disorder due to a deficiency of arylsulphatase A activity. According to the age of onset of symptoms three different forms of the disease are described: late infantile, juvenile and adult types. We report the clinical, neuroimaging, biochemical and morphological features in a man in which the first symptoms ensued at the age of 39. In this patient, whose clinical manifestations were represented by "psychiatric" symptoms, the onset was particularly late in comparison with the large majority of the previously reported cases.     

Seizures as a presenting feature of late onset metachromatic leukodystrophy

OBJECTIVES: We describe 2 patients with epilepsy as an early manifestation of late onset metachromatic leukodystrophy (MLD). METHODS AND RESULTS: The first patient presented with epileptic seizures at the age of 34 years while neurological and cognitive abnormalities appeared later. MRI findings were compatible with leukodystrophy and low levels of arylsulphatase-A activity confirmed MLD. The second patient developed epileptic seizures and behavioral disturbances at the age of 19 years. She remained stable and seizure free for 8 years. Afterwards she developed uncontrolled epileptic seizures and status epilepticus as well as neurological and cognitive impairment. Leukodystrophy was diagnosed by MRI findings and low levels of arylsulphatase-A activity were compatible with MLD. CONCLUSION: Our 2 cases postulate that epileptic seizures may be an early and prominent manifestation of late onset MLD.     

Ultrastructural findings of peripheral nerve in a preclinical case of adult metachromatic leukodystrophy.

In a 13-year-old neurologically healthy boy from a family with adult-onset of metachromatic leukodystrophy (MLD) showing arylsulfatase A-deficiency in the adult, sural nerve biopsy probably was performed 2-3 decades before clinical manifestation of the disease could be expected. Ultrastructurally 4 basic types of inclusion bodies in Schwann cells could be demonstrated (pleo-morphic "zebra body"-like inclusions, double-lamellated inclusions, "tuff-stone"-like inclusions, granular osmiophilic inclusions). Additionally, endoplasmatic reticulum, mitochondria and lysosomes showed marked alterations. Advanced damage of myelin was only rarely seen, but initial segmental demyelination was a common finding. These early pathological changes in chronic MLD are thought to represent a subcellular metabolic insufficiency of Schwann cells in this disease.     

Congenital metachromatic leukodystrophy

Summary The pathologic findings of a case of congenital metachromatic leukoencephalopathy are described in a newborn infant who died 20 hours after birth. Metachromatic material was found particularly in cerebral white matter. No metachromatic material was demonstrated, however, in central nervous system neurones or in cells of kidneys, lymph nodes and liver where large, vacuolated cells were found, probably because of the easy solubility in formalin of the deposited substance.

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Zusammenfassung Es werden die pathologischen Befunde eines Falles von angeborener metachromatischer Leukoencephalopathie bei einem Neugeborenem, das 20 Std post partum starb, geschildert. Metachromatisches Material war vor allem im Großhirnmark vorhanden, nicht jedoch in Neuronen, in den Nieren, in Lymphknoten und in der Leber, wo sich große vacuolosierte Zellen fanden, vermutlich weil die Speichersubstanz durch Formalin herausgelöst wurde.

     

Adult metachromatic leukodystrophy

An adult case of metachromatic leukodystrophy confirmed by characteristic findings of the brain and superficial sural nerve biopsies, but with absence of deficiency of arylsulfatase A activity in the leucocytes, was reported. Ultrastructurally, typical membrane-bound inclusions were found in white matter and Schwann cells. The long course of thirty years and late onset of illness were discussed.     

The fatty acid composition of cerebrosides and sulfatides in a case of adult metachromatic leukodystrophy

Summary The fatty acid composition of cerebrosides and sulfatides in the white matter of a brain from a patient with adult MLD was analysed by gas-liquid chromatography and compared to the results obtained from a normal control of the same age. In adult MLD a relative increase of short chain fatty acids affecting mainly the cerebrosides and also a diminution of unsaturated fatty acids affecting mainly the sulfatides were found. The whole composition of the sulfatides was altered to a larger extent than of the cerebrosides and this result was in contrast to results obtained in infantile MLD. These findings were discussed on the basis of a similar enzymatic defect in both adult and infantile cases and with regard to a chronic demyelinating process.Dedicated with gratitude and affection to Prof. H. J. Bauer on the occasion of his 60th birthday.     

Infantile metachromatic leukodystrophy in twins

The authors report two cases of infantile metachromatic leucodystrophy in monozygotic female twins, born from a second cousin marriage (f = 1/32). The zygosity was determined by means of obstetrics and genetics marker findings.