The authors reviewed the incidence of cancer, repetitive nerve stimulation findings, and response to treatment in 73 patients with Lambert-Eaton myasthenic syndrome. Thirty-one patients (42%) had lung cancer, 29 small cell. Doubling of the compound motor action potential amplitude in three tested distal muscles was seen in only 41% of patients. Treatment with 3, 4-diaminopyridine produced moderate to marked self-reported functional improvement in 79% of the 53 treated patients.

Familial vitamin E deficiency (AVED) causes ataxia and peripheral neuropathy that resembles Friedreich's ataxia. AVED is thought to be caused by a defect in the transport of vitamin E in liver cells, which is the probable function of alpha-tocopherol transfer protein (alphaTTP). We have cloned the cDNA and several genomic phage clones covering the entire human alphaTTP gene and determined the junctions between the five exons and four introns that composed the gene for human alphaTTP. Three mutations in three unrelated North American families with AVED were identified. Two mutations, 485delT and 513insTT, cause a frame shift and a premature stop codon and the third mutation 574G-->A would substitute Arg192 to His in alphaTTP. The 2 patients with a severe form of AVED were homozygous with 485delT and 513insTT, respectively, while the patient with a mild form of the disease was compound heterozygous with 513insTT and 574G-->A. These findings have identified the underlying genetic defect in AVED and have confirmed the role of alphaTTP in AVED.

We report the identification of a new locus for autosomal dominant limb-girdle muscular dystrophy (LGMD1) on 7q. Two of five families (1047 and 1701) demonstrate evidence in favor of linkage to this region. The maximum two-point LOD score for family 1047 was 3.76 for D7S427, and that for family 1701 was 2.63 for D7S3058. Flanking markers place the LGMD1 locus between D7S2423 and D7S427, with multipoint analysis slightly favoring the 9-cM interval spanned by D7S2546 and D7S2423. Three of five families appear to be unlinked to this new locus on chromosome 7, thus establishing further heterogeneity within the LGMD1 diagnostic classification.

No abstract