Steven M. Leber

Periaxin mutations cause recessive Dejerine-Sottas neuropathy.

The periaxin gene (PRX) encodes two PDZ-domain proteins, L- and S-periaxin, that are required for maintenance of peripheral nerve myelin. Prx(-/-) mice develop a severe demyelinating peripheral neuropathy, despite apparently normal initial formation of myelin sheaths. We hypothesized that mutations in PRX could cause human peripheral myelinopathies. In accordance with this, we identified three unrelated Dejerine-Sottas neuropathy patients with recessive PRX mutations-two with compound heterozygous nonsense and frameshift mutations, and one with a homozygous frameshift mutation. We mapped PRX to 19q13.13-13.2, a region recently associated with a severe autosomal recessive demyelinating neuropathy in a Lebanese family (Delague et al. 2000) and syntenic to the location of Prx on murine chromosome 7 (Gillespie et al. 1997).

GENE TRANSFER USING REPLICATION-DEFECTIVE RETROVIRAL AND ADENOVIRAL VECTORS

Publisher Summary This chapter discusses gene transfer using replication-defective retroviral and adenoviral vectors. Viruses are obligate intracellular parasites that live by invading a host cell and then using that cells machinery to replicate their genetic material. As the understanding of viral genomes and their lifestyle has increased, it has been natural to envision harnessing their skills for the transfer of exogenous genes to vertebrate cells in vivo, both for experimental purposes and for gene therapy. Numerous viral vectors have been studied in these contexts, including retrovirus, adenovirus, herpes virus, sindbis virus, vaccinia virus, and adeno-associated virus. Retroviruses consist of an RNA genome encased in a protein core, which in turn is coated by a proteolipid envelope. The RNA encodes three classes of proteins called “pol” (for polymerase), “gag” (for group-associated antigens), and “env” (for envelope). The pol proteins are tightly associated with the RNA, gag proteins form the core, and env proteins are embedded in the lipid membrane.

Leigh Syndrome in a Girl With a Novel DLD Mutation Causing E3 Deficiency

We present the biochemical and molecular diagnosis of dihydrolipoamide dehydrogenase deficiency (also known as E3 deficiency) and Leigh syndrome in a 14-year-old girl with learning disability and episodic encephalopathy and ketoacidosis. The diagnosis was based on values of plasma amino acids and urine organic acids, obtained during acute encephalopathy, lactic ketoacidosis, and liver failure, precipitated by infectious mononucleosis. Enzymatic and molecular analyses confirmed dihydrolipoamide dehydrogenase deficiency. E3 activity from cultured skin fibroblasts ranged from 9-29% of the mean. Molecular analysis revealed compound heterozygosity for novel and known pathogenic mutations (p.I353T and p.G136del, respectively). The patient received dietary augmentation and continuous renal replacement therapy, given her severe, persistent lactic acidosis. Acute decompensation resulted in magnetic resonance imaging changes involving the posterior aspect of the putamen, lateral, and medial thalami, substantia nigra, lateral geniculate bodies, and splenium of the corpus callosum. The cortex and subcortical white matter of the right and left occipital lobes and perirolandic region were also affected. In our review of molecularly confirmed patients with dihydrolipoamide dehydrogenase deficiency, Leigh syndrome was common. Our patient, whose most severe decompensation occurred at a more advanced age than previously reported, provides further evidence of the heterogeneous presentations of dihydrolipoamide dehydrogenase deficiency.

Infarction of basal ganglia associated with California encephalitis virus

A child developed acute hemiparesis due to infarction of basal ganglia and internal capsule. Pleocytosis of cerebrospinal fluid and elevated immunoglobulin M antibodies suggest that California encephalitis virus infection caused the stroke.

The Internet and clinical practice of child neurology.

The Internet has great potential for aiding patient care. Concerns regarding patient confidentiality, provider liability, and efficient and fair use of these new resources have triggered specific recommendations for integration of the Internet into our practices.

Pediatric Somatic Symptom and Related Disorders: Primary Care Provider Perspectives:

Somatization, or physical symptoms that are inconsistent with a physiological cause that may or may not involve an identified stressor, is common in outpatient pediatrics. When these symptoms persist, they can impair function and progress to a somatic symptom and related disorder (SSRD), resulting in increased health care use and increased demands on primary care providers (PCPs). We performed a needs assessment among PCPs to better understand how best to support providers caring for children with SSRDs. Pediatric PCPs (n = 77) were surveyed to better understand their training, experience, perceptions, and practices of SSRD care. Findings indicate that PCPs have limited training in SSRD care but express interest in learning more. Many barriers to effective care were reported. We hope to use these findings to develop training materials and support services for pediatric PCPs managing SSRDs.

The Webster’s dictionary Neurologists on the Internet

The Web . . . is a mingled yarn, good and ill together. (Shakespeare, All’s Well that Ends Well, Act 4, Scene 3) Neurology is making a slow and gradual appearance on the Internet. An informal survey of neurologists indicated that the most widely used Internet activity was e-mail. The article by Dr. Rivner1 in this issue of Neurology documents the activity of a neurologists’ listserver. A listserver is not a concept familiar to all. In essence, it facilitates dissemination of messages to a group of people with similar interests: the “list.” The difference between this and a newsletter is that any message sent to the list by an individual member is then instantly sent to all the members on the list. For some years, Dr. Rivner has supervised such a listserver—the Neurolist—and he has summarized his experience here. It is obvious from the activity on Neurolist that this is a resource which neurologists use and appreciate. Certain aspects are noteworthy. First, the international participation is substantial, making this truly a worldwide resource. Second, 70% of the messages are either case discussions or neurologic discussions, implying that this may influence how neurologists manage individual cases. In this context, Dr. Rivner asserts that Neurolist has improved medical care. This may be so, but …