Autosomal recessive familial amyotrophic lateral sclerosis (RFALS) is a rare form of ALS that usually presents at an early age with slow progression of symptoms. RFALS is clinically and genetically heterogeneous and the locus of RFALS type 3 was mapped to 2q33 (ALS2) in a single family. We now report linkage of a more-common form of RFALS to chromosome 15q15-q22 markers (ALS5) and show further genetic locus heterogeneity in RFALS. ALS5 is the locus for most families with RFALS and appears to be present in both North African and European populations.
Reverse transcriptase-polymerase chain reaction (RT-PCR) on 24 cerebrospinal fluid (CSF) specimens collected between February and August 1992 detected genome sequence of West Nile (WN) virus in 8 specimens and Japanese encephalitis (JE) virus in a single specimen. The results, combined with the data by IgM-ELISA on CSF indicated that a significant proportion of acute encephalitis cases in Karachi, Pakistan, were caused by WN virus infection, while JE virus caused a small fraction.
Neurological diseases, especially subacute sclerosing panencephalitis (SSPE), were surveyed in Karachi, Pakistan disclosing following major results. (1) Indirectly estimated prevalence rates of selected neurological disease entities were comparable with the rates from western countries and Japan in heredodegenerative diseases, but grossly elevated in infectious diseases. (2) Estimated mortality statistics for the Karachi community revealed highly elevated rates for infectious, parasitic and perinatal causes of death. (3) SSPE represented about 10% of inflammatory afflictions of the cerebral parenchyma, its incidence rate being about 100% times more than that observed in developed countries. A case-control study preliminarily showed that infants who later contract SSPE have unhealthy mothers, are born small, and have various occurrences of ill health from birth to the onset of SSPE. (4) Age at the onset of measles was very young in the cases as well as in controls, unlike the average young age at onset of cases only in developed countries. Measles contracted at young age is a well known risk factor to SSPE. Whereas few children in developed countries acquire measles at such an early age, many Karachi children do. Elevated occurrence of SSPE is probably conditioned by such age patterns of measles infection, together with other risk factors more common in Karachi due to poorer health standards. A proper immunization programme is urgently needed to control measles and SSPE.
The prevalence of West Nile (WN) virus infection in Karachi, Pakistan, was unknown until 1982. It had been noticed that there were more than a few patients with encephalitides in Karachi, and it was supposed that Japanese encephalitis (JE) cases would be found among them. Therefore, a seroepidemiological study was conducted to define the prevalence of WN virus infection and the possible occurrence of JE virus infection in the Karachi area. Prevalences of haemagglutination inhibition (HI) and neutralization (NT) antibodies against WN virus were studied among 81 serum samples (in July, 33 samples; in September, 48) during 1983, and among 156 paired serum samples that were collected twice, in July and October of 1985. Nearly the same antibody-positive rates were obtained in July of both years (1983: HI 55%; 1985: HI 53%; NT 50%); the rates increased slightly during September/October (1983: HI 65%; 1985: HI 59%, NT 54%). Among 156 paired samples in 1985, 20 (13%) and 12 (8%) showed positive- or negative-antibody conversion between July and October. Two serum samples from each of 156 residents obtained in July had a significantly higher NT antibody titre against JE virus than against WN virus (in case 1, JE 1:80, WN less than 1:10; in case 2, JE 1:40, WN less than 1:10). This is the first report to show the prevalence of WN virus infection in Karachi, Pakistan.
Subacute sclerosing panencephalitis (SSPE) in Western countries and Japan is found more often in early- than in late-measles sufferers. Recent SSPE findings in Karachi, however, present a different picture. Age at measles contraction was obtained and analyzed for 44 SSPE patients identified in Karachi between 1983 and 1988. The ratios of early- (< 2 years of age) and late- (> 2 years of age) measles sufferers among 36 of these patients who had experienced only one attack of measles were 0.33 and 0.67, respectively. This is in striking contrast to the predominance of early measles in the SSPE histories reported in Japan and an number of Western countries.
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