[Connatal type of Pelizaeus-Merzbacher disease: a case report].

Pelizaeus-Merzbacher disease (PMD) is a hereditary disorder with myelin dysplasia in the central nervous system. The connatal type is a more severe form compared to the classical type and shows developmental arrest or deterioration, nystagmus, spasticity, and/or convulsions in the neonatal period. A 1 1/4-year-old Japanese boy diagnosed as connatal type PMD is reported here. Soon after his birth, he demonstrated horizontal and rotatory nystagmus and opisthotonic posture. At the age of 10 months, he had difficulty in feeding. At the age of 1 year, he presented more severe opisthotonic posture and frequent vomiting. He showed deterioration in gross motor development. His chromosome analysis showed a normal male karyotype. Electroencephalogram did not show a sleep spindle. Auditory evoked brainstem responses (ABR) showed only wave I on both sides. Visual evoked potentials (VEP) showed prolongation of latencies. These results were compatible with PMD. Nuclear magnetic resonance imaging (MRI) demonstrated in the white matter of cerebrum and brainstem no high intensities on T1-weighted images and diffuse high intensities on T2-weighted images. Such absence of myelination including the brainstem was characteristic to the connatal type PMD. The diffuse disturbance of myelination appeared to correlate with the severity of clinical symptoms.

Neurophysiologic studies and MRI in Pelizaeus-Merzbacher disease: comparison of classic and connatal forms.

Four patients with the classic form and 1 patient with the connatal form of Pelizaeus-Merzbacher disease were studied with magnetic resonance imaging, electroencephalography, and multimodal evoked potentials, including brainstem auditory evoked potentials, somatosensory evoked potentials, and visual evoked potentials. Comparisons between these findings were made. It was determined that the neurophysiologic studies, particularly brainstem auditory evoked potentials, are of value in early diagnosis of Pelizaeus-Merzbacher disease; brainstem auditory evoked potentials with only normal wave I may be a relatively reliable clue suggesting the classic form of Pelizaeus-Merzbacher disease in patients with nystagmus and chronic progressive encephalopathy. Magnetic resonance imaging allows an accurate assessment of the degree of hypomyelination; however, the clinical severity of various forms of Pelizaeus-Merzbacher disease seemed to be independent of the age of onset and the amount of residual myelin. The following may be distinguishing features between the connatal and classic forms of Pelizaeus-Merzbacher disease: hypoplasia of the cerebellum and brainstem, and diffuse brain atrophy on magnetic resonance imaging; optic atrophy with abnormal visual evoked potential; seizure disorder with abnormal electroencephalography, and/or auditory nerve impairment with abnormal wave I of brainstem auditory evoked potentials in the early stage of the disease.

[Neonatal adrenoleukodystrophy. Apropos of 3 cases in siblings]. / Adrénoleucodystrophie néonatale. A propos de trois cas d'une même fratrie.

Neonatal adrenoleukodystrophy is a recently individualized disease manifested by very early onset of neurologic deterioration. Progression of the disease is rapid and there is no effective therapy. Differences with X-linked adrenoleukodystrophy include genetic inheritance, which is autosomal recessive, a more severe prognosis, and presence of multiple peroxisome enzyme deficiencies that justify classification alongside the Zellweger syndrome among the peroxisome disorders. We report three cases in siblings and describe the main clinical and biochemical features.

Neonatal adrenoleukodystrophy: new cases, biochemical studies, and differentiation from Zellweger and related peroxisomal polydystrophy syndromes.

Eight new cases of autopsy-confirmed or suspected neonatal adrenoleukodystrophy (NALD) are presented together with new biochemical data on very-long-chain fatty acids (VLCFA) and plasmalogens and a review of all previously published cases. The clinical, biochemical, and histopathologic abnormalities characteristic of this newly recognized form of adrenoleukodystrophy are analyzed in detail and compared to the principal characteristics of the similar disorder, the cerebrohepatorenal syndrome of Zellweger (ZS). Using strict pathologic criteria for the diagnosis of NALD, we find that, despite many clinical resemblances, NALD and the ZS are distinguishable on the basis of histology and peroxisomal biochemistry. Patients with NALD demonstrate adrenal atrophy, systemic infiltration by abnormal lipid-laden macrophages, and elevations of saturated VLCFA. In contrast, patients with ZS have chondrodysplasia, glomerulocystic disease of the kidney, central nervous system dysmyelination, and elevations of unsaturated as well as saturated VLCFA, but they lack adrenal atrophy. We conclude that NALD and the ZS probably represent at least two different genetic defects.

Cerebro-hepato-renal (Zellweger) syndrome, adrenoleukodystrophy, and Refsum's disease: plasma changes and skin fibroblast phytanic acid oxidase.

Cerebro-hepato-renal (Zellweger) syndrome, adrenoleukodystrophy, and Refsum's disease patients can be divided into at least five distinct groups, according to the nature of their plasma changes and their fibroblast phytanic acid oxidase activities. The biochemical changes in the plasma vary from an increase in a single metabolite or group of structurally related metabolites, such as in X-linked adrenoleukodystrophy (ALD) and classical Refsum's disease, to an increase in a number of structurally distinct metabolites, as in neonatal ALD/Zellweger syndrome, and infantile Refsum's disease. All patients, with the exception of those with the X-linked form of adrenoleukodystrophy are deficient in phytanic acid oxidase activity. The great similarity observed in neonatal adrenoleukodystrophy/Zellweger syndrome and infantile Refsum's disease suggests that the basic biochemical lesion in each may be similar or at least closely related.

Connatal Pelizaeus-Merzbacher disease with congenital stridor in two maternal cousins.

Two maternal cousins are described with the connatal form of Pelizaeus-Merzbacher Disease (PMD) and congenital stridor. Study of brain biopsy material confirms the diagnosis of PMD. The neuropathological findings are suggestive for the transitional form of this disease. Quantitative morphology gives support to the hypothesis that PMD is a disturbance in maturation of neurons and in myelin formation rather than an active degenerative process. The hereditary transmission is most consistent with a sex-linked recessive pattern. Different X-linked signs seem combined in the presented cases.

Congenital Pelizaeus-Merzbacher disease (Seitelberger type), malformation and cystic degeneration of the central nervous system.

The present paper reports on the case of a neonate child with multiple malformations affecting osteogenesis and the central nervous system (microcephaly, pachygyria). Morphologically, myelin staining supplied evidence of the total lack of myelin sheaths (myelin aplasia). The cerebellar cortex was malformed and altered by cystic degeneration. Electron microscopy confirmed the aplasia of the myelin sheaths and revealed the presence of concentric multilamellar formations in the glial cells (myelination glia), and in areas of cystic degeneration. The morphologic aspects clearly showed the relationship of this congenital aplasia of the myelin sheaths with the congenital Pelizaeus-Merzbacher disease (Seitelberger type). The cystic degeneration differs from the spongy degeneration of the brain (van Bogaert-Bertrand disease) and should be considered a result of maldeveloped nervous tissue.

Seitelberger's connatal form of Pelizaeus-Merzbacher Disease. Case report, clinical, pathological and biochemical findings.

A case of Seitelberger's connatal form of Pelizaeus-Merzbacher disease is reported. He lived to the age of 13 and was able to recognize persons. Both is unusual in this disease. Some of the few myelin sheaths had two different periodicities (150 and 90 A). Intranuclear inclusions similar to Hirano's cytoplasmic eosinophilic rodlets were observed. The findings of connatal form of Pelizaeus-Merzbacher disease are compared with those of dysmyelinating mice (Jimpy and Quacking) and of manipulated myelinating tissue cultures. The possibility is considered, that the alterations in these dysmyelinating human and animal conditions are caused by extraneural circulating factors.