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).
ABSTRACT. The Food and Drug Administration licensed a live-virus varicella vaccine (Varivax In March 1995, the Food and Drug Administration approved a live-attenuated varicella vaccine for use in healthy individuals 12 months of age and older. The vaccine has been shown to be safe and effective in healthy children and adults, 1,2 as well as in children with leukemia. [3][4][5] The American Academy of Pediatrics does not recommend routine screening of children for human immunodeficiency virus (HIV) infection before vaccination. In addition, routine administration of varicella vaccine is not recommended for all HIV-infected children. 6 Significant morbidity and mortality is caused by varicella-zoster virus (VZV) in immunocompromised individuals, including those infected with HIV. 7-9 Postexposure varicella-zoster immune globulin prophylaxis decreases the likelihood and severity of varicella in high-risk individuals, but the breakthrough rate can be as high as 26%. 4,5 Exposures to varicella are often not recognized, further limiting the utility of postexposure prophylaxis. Immunization, on the other hand, has the potential of establishing permanent immunity. After primary infection in HIV-infected adults, the risk of reactivation remains low well into the progression of acquired immunodeficiency syndrome. These individuals are at risk of developing zoster, but have a relatively low risk of dissemination. 8 This suggests that the immunization of HIV-infected children could prevent primary (wild-type) infection, thereby eliminating viral entry into dorsal root ganglia 3 and subsequent reactivation.Immunization of immunocompromised patients has been limited to children with leukemia and solid tumors following strict guidelines to limit the potential for serious adverse events. 5 Routine immunization of all healthy children carries the potential risk that unrecognized immunocompromised children could be inadvertently vaccinated. Reported here is a 16-month-old, previously undiagnosed, HIV-infected boy who developed dissemination of the vaccine strain of varicella zoster virus after routine immunization. CASE REPORTA previously healthy 16-month-old boy who was admitted to the University of Michigan Mott Children's Hospital with a 5-day history of increasing respiratory distress, fever (101°F), cough, emesis, and lower extremity weakness. In addition, he had a 1-month history of a progressive erythematous papular rash, which began in the groin and upper right thigh progressing to involve the trunk, axilla, and right knee and foot. The rash was associated with a low-grade fever and the patient had recently been refusing to walk for several days. On admission, he had a pulse of 173 beats/min, and a respiratory rate of 24 breaths/min. Weight (9 kg), height (74 cm), and head circumference (45 cm) were all below the fifth percentile. Physical examination was remarkable for oral thrush, diffuse rhonchi, and scattered wheezes, and a confluent macular rash over the trunk and arms. There was also an erythematous zosteriform patc...
We present the biochemical and molecular diagnosis of dihydrolipoamide dehydrogenase (DLD) deficiency (also known as E3 deficiency) and Leigh syndrome in a 14 year-old girl with previous history of learning disability and episodic encephalopathy and ketoacidosis. The diagnosis was suggested by biochemical laboratory values from plasma amino acids and urine organic acids, which were obtained during an acute episode of encephalopathy, lactic ketoacidosis and liver failure all precipitated by infectious mononucleosis. DLD deficiency was confirmed via enzymatic and molecular analyses. E3 activity from cultured skin fibroblasts ranged between 9% and 29% of the mean. Molecular analysis showed compound heterozygosity for novel and previously reported pathogenic mutations; p.I353T and p.G136del, respectively. The patient was managed using a combination of dietary augmentation as well as continuous renal replacement therapy given her severe and persistent lactic acidosis. Her acute decompensation resulted in brain MRI changes involving the posterior aspect of the putamina, lateral and medial thalami, substantia nigra, lateral geniculate bodies and splenium of the corpus callosum. Additional affected regions included the cortex and subcortical white matter of the right and left occipital lobes and the peri-rolandic region. We review the literature of molecularly confirmed patients with DLD deficiency and note that Leigh syndrome is common in reported patients. This case provides further evidence of the heterogeneous presentation of DLD deficiency as our patient presented with her most severe decompensation at an age much more advanced than in previously reported patients.
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