Defective biosynthesis of proteolipid protein in Pelizaeus-Merzbacher disease.

The brain of an 18-year-old patient with Pelizaeus-Merzbacher disease was examined by standard neuropathological and biochemical methods and by immunocytochemical and immunochemical techniques. Analysis revealed a lack of myelin-specific lipids, but showed a residual immunoreactivity for myelin basic protein, myelin-associated glycoprotein, and 2',3'-cyclic nucleotide-3'-phosphodiesterase. Examination by immunocytochemistry and enzyme-linked immunosorbent assay showed an absence of proteolipid apoprotein (lipophilin). The peripheral nervous system was normal. Pelizaeus-Merzbacher disease in humans shares many neuropathological and biochemical features with X-linked mutations in animals, e.g., the jimpy mouse and myelin-deficient rat. The specificity of this protein deficiency in Pelizaeus-Merzbacher disease gains additional support from the recent mapping of the lipophilin gene to the human X chromosome.

Olivopontocerebellar atrophy: immunocytochemical and Golgi observations.

Brain tissue was obtained promptly after death from a patient with autosomal dominant olivopontocerebellar atrophy and studied by immunocytochemistry and a Golgi technique. Antiglutamic acid decarboxylase showed severe loss of Purkinje cells and their terminals in the dentate nucleus. Stains for neuron-specific enolase (NSE) and microtubule-associated proteins (MAP) confirmed the integrity of the dentate nucleus. Basket and stellate cells revealed secondary changes, but Golgi neurons were intact. Methods for NSE and MAP disclosed dendritic alterations and loss of neurons in the basis pontis and inferior olivary nuclei. Golgi impregnation of Purkinje cells showed loss of major dendrites, paucity of spiny branchlets, and axonal expansions.

Infantile facioscapulohumeral muscular dystrophy: new observations.

Clinical, electrodiagnostic, and biopsy findings in a family with infantile facioscapulohumeral muscular dystrophy are reported. Four of eight family members having the disorder, all with onset in infancy, developed severe weakness leading to death in adolescence. The clinical course and prognosis of infantile facioscapulohumeral muscular dystrophy may, therefore, be as devastating as that of Duchenne muscular dystrophy. The unusual infantile presentation and high mortality in our affected family members suggest that the gene coding for this disorder may be different from that responsible for conventional facioscapulohumeral muscular dystrophy.

Benign muscular dystrophy with contractures: a new syndrome?

Three patients are described with muscular dystrophy and contractures. Although this disorder bears similarities to Emery-Dreifuss disease and variants previously described, absence of cardiomyopathy is a distinguishing feature. Electrodiagnostic testing and muscle biopsy are consistent with a myopathy. An autosomal dominant pattern of inheritance is suspected, but the possibility of a Y-to-Y transmission cannot be completely excluded.

Familial amyloid polyneuropathy.

Amyloid fibrils were isolated from the myocardium of two patients with familial amyloid polyneuropathy. The solubilized amyloid fibril whole protein shared immunologic determinants with normal human serum prealbumin (transthyretin), but revealed subtle differences on immunoelectrophoresis and radial immunodiffusion. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, amyloid fibril whole protein was resolved into numerous bands that reacted with antitransthyretin on immunoblots. The whole protein also contained peptide fragments of fibronectin, but was devoid of amyloid P protein. An antiserum raised against the whole protein was suitable for immunocytochemistry of amyloid in paraffin sections. In contrast, commercial antitransthyretin, raised against the intact tetrameric protein failed to react with tissue amyloid. Immunochemical and immunocytochemical results support the concept that familial amyloid polyneuropathy with cardiomyopathy is due to infiltration of susceptible tissues by an anomalous transthyretin.

Huntington's chorea. Its impact on the spouse.

Huntington's chorea imposes a direct imprint on the life of the spouse of the affected patient. Interviews with 15 wives of patients with Huntington's chorea revealed that none of them knew prior to marriage of the presence of a heritable disease within the husband's family. When informed of the diagnosis, the wife reacted with disbelief and denial. As she became aware of the steady progression of the disease and the threat of transmission to her children, her response changed to resentment and hostility. The disease permeated the entire life of the unaffected spouse: her life style, family responsibility, goals, and marital relationship. In essence, the wife became inextricably involved in the disease and suffered continuous trauma from it.

Adult-onset hereditary ataxia in Scotland.

A systematic search for cases of adult-onset hereditary ataxia was conducted on location in Scotland. The investigation resulted in the discovery of eight pedigrees with 42 patients of whom 16 were alive in 1975. Nine patients were examined by the authors and recent hospital records were available on the remaining seven. The clinical features were quite variable. In declining order of frequency, findings were gait and limb ataxia, dysarthria, hyperreflexia, extrapyramidal motor disturbances, impaired vibratory sense, spasticity, defects of extraocular movements and nystagmus, reflex depression, Babinski signs, impaired joint position sense, muscle weakness, optic atrophy, and mental abnormalities. Foot deformity occurred only once. Inheritance was compatible with autosomal dominant transmission, but complicated by consanguinity in two families. The minimum prevalence was calculated as 0.31/100,000. Autopsy in two members in one family revealed olivopontocerebellar degeneration.

Supranuclear ophthalmoplegia in olivopontocerebellar degeneration.

Autosomal dominant olivopontocerebellar degeneration was diagnosed in a family of Scottish ancestry by clinical examination and autopsy. In addition to having progressive cerebellar ataxia, head titubation, and severe dysarthria, the patients are unable to initiate saccadic eye movements. Slow pursuit movements are normal. Reflex movements of the eyes caused by passive rotation or caloric labyrinthine stimulation are not impaired but are not associated with nystagmus. The phenomenon can be classified as supranuclear pseudo-ophthalmoplegia. It differs from congenital ocular motor apraxia in age at onset and the absence of random eye movements. The anatomic lesion responsible for the defect of saccadic eye movements remains to be established.