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Objective: Reducing body myopathy (RBM) is a rare progressive disorder of muscle characterized by intracytoplasmic inclusions, which stain strongly with menadione-NBT (nitroblue tetrazolium). We recently identified `the four and a half LIM domain gene FHLI located on chromosome Xq26 as the causative gene for RBM. So far eight familial cases and 21 sporadic patients with RBM have been reported in the literature. Methods: We ascertained a total of 8 members of a German family initially reported by Goebel et al. as a mixed myopathy with rigid spine myopathy and reducing as well as cytoplasmic bodies. Clinical findings in the original and additional family members have been reviewed. Mutation detection was performed by direct sequencing of FHLI exons. Results: We identified a novel mutation (p.C15OR) in the second LIM domain of FHLI in six family members (1 male, 5 females). The male index patient was the most affected member presenting with rigid spine, followed by rapidly progressive muscle weakness. He died from the consequences of respiratory insufficiency at the age of 29.5 years. His sister, mother, grandmother, aunt and female cousin all carried the mutation in the heterozygous state. The sister is clinically unaffected; their mother had myopathic changes in her muscle biopsy, while the grandmother showed first signs of weakness at 50 years of age. The 54-year-old aunt and her daughter are clinically asymptoniatic. Conclusion: We report a novel LIM2 domain mutation in FHLI in a previously reported family with RBM with cytoplasmic bodies and spinal rigidity. While the male index patient was significantly affected, female carriers show varying manifestations and may be asymptomatic, likely reflecting varying degrees ofX-inactivation. RBM continues to be associated with mutations in the LIM2 domain of FHL1. We also confirm our earlier observation that mutations at the N-terminal end of the LIM2 domain seem to be milder compared to mutations seen at the C-terminal part of the domain which cause severe disease even in female carriers. [ABSTRACT FROM AUTHOR]

The clinical, neurophysiological and neuroradiological work-up as well as the results of a specific treatment trial are presented of the first patient diagnosed with beta-ureidopropionase deficiency (E.C. 3.5.1.6, McKusick 606673). The patient presented with an early-onset dystonic movement disorder, severe developmental delay with marked impairment of visual responsiveness in combination with severely delayed myelination in magnetic resonance imaging studies. In addition, there were partial optic atrophy, pigmentary retinopathy and mild cerebellar hypoplasia. The enzyme defect was expected to lead to intracerebral deficiency of beta-alanine which seems to be a neuromodulator at inhibitory synapses. Therefore, a therapeutic trial with supplementation of beta-alanine was undertaken over 1.5 years with no convincing clinical improvement.

The merosin M-chain (or laminin-alpha 2) is one of three subunits of laminin-2 which is highly expressed in striated muscle and peripheral nerve. Complete lack of laminin-alpha 2 expression in skeletal muscle is the hallmark of one form of congenital muscular dystrophy which is characterized by dysmyelination of the central nervous system (CNS), links to chromosome 6q2 and is common among Caucasians. Laminin-alpha 2 expression was also found to be significantly reduced in Fukuyama congenital muscular dystrophy which links to chromosome 9q3. We report consistently preserved laminin-2 expression, including laminin-alpha 2, as detected by immunofluorescence in skeletal muscle from five patients with Walker-Warburg syndrome which is characterized by congenital muscular dystrophy and, in addition, type II lissencephaly or pachygyria, defective CNS myelination, and ocular dysgenesis. These findings show that in spite of partial phenotypic overlap between Fukuyama CMD and Walker-Warburg syndrome the two disorders are nosologically separate disease entities. They also exclude that Walker-Warburg syndrome is allelic to the common form of congenital muscular dystrophy with laminin-alpha 2 deficiency.

Using real-time ultrasound imaging normal values were obtained for quadriceps muscle thickness and subcutaneous tissue depth in the first year of life from 120 normal infants. These values were corrected for weight and height by introduction of a "correcting factor". In addition, a "modified muscle index" was calculated by multiplying the ratio of muscle to subcutaneous tissue thickness with the correcting factor and showed a steady increase from birth (mean 2.1) to the end of the first year (mean 4.8). The study of 12 patients with spinal muscular atrophy type I (SMA I) revealed that 9 out of 12 SMA I patients failed to reach the 3rd percentile for the muscle to subcutaneous tissue ratio and 10 out of 12 were well below the 3rd percentile for the modified muscle index due to their muscle atrophy. Only the two youngest SMA I patients aged 4 and 6 weeks reached values on the 3rd percentile. In contrast, 10 patients with myopathy and one patient with holoprosencephaly showed values within the normal percentiles even in the presence of severe clinical muscle weakness and signs of atrophy on muscle histology. In the differential diagnosis of early onset myopathy, atrophy of the quadriceps muscle during the first months of life in the absence of markedly increased echodensity seems to be a pathognomonic finding for SMA.

We report the neurological findings in two children with AIDS and one child with lesser AIDS. The first patient developed acute encephalopathy 37 months after having received a blood transfusion from a HTLV-III positive donor. CCT showed ring-enhancement and hypodense lesions with homogenous enhancement. Autopsy revealed CNS toxoplasmosis. The second child with AIDS, born to an iv drug-addicted mother, had one seizure at four months of age, but other neurologic signs were absent. She died of pneumonia due to Pneumocystis carinii at seven months of age. Postmortem examination of the brain revealed extensive nerve cell damage in the cerebral cortex and cerebellum, probably due to terminal hypoxemia and not AIDS-related. In both children clinical features of childhood AIDS like failure to thrive, lymphadenopathy, oral thrush and chronic pulmonary infiltrates were absent. The hallmark of the third child's clinical course was a progressive loss of psychomotor abilities with onset of the neurological symptoms nine months before other signs of AIDS occurred. AIDS should be suspected or excluded in children at increased risk for AIDS presenting with either acquired atypical CNS infection or unexplained developmental regression, even in the absence of other clinical symptoms of pediatric AIDS.