Difficulties in the Diagnosis of Gaucher Disease in a Low-Income Country: A Case Report from Mozambique

Abstract Introduction: Gaucher disease (GD) is one of the common lysosomal storage disorder (LSD) with an estimated frequency of one in 40,000 newborns globally. GD is an autosomal recessive condition, which results from mutations in the GBA1 gene, causing partial or complete deficiency of β-glucocerebrosidase enzyme activity, which leads to the widespread accumulation of the substrate glucosylceramide. Aims: This report presents different challenges of clinical management and communication between medical specialties to reach diagnose of any rare disease in Mozambique, a low-income country, which health system has limited infrastructure, trained personnel, and budget for diagnosis and to provide treatment for rare genetic disorders such as GD. Case Presentation: The patient was a 15-year old black female patient of Mozambican nationality born from non-consanguineous parents. Three of the four patient's siblings were healthy; one sister had died of a disease with a similar clinical features. Our patient presented with abdominal distention and hepatosplenomegaly. Blood tests revealed pancytopenia and a high level of ferritin. Liver biopsy and histologic examination revealed infiltration of the splenic parenchyma and portal area of the liver as well as enlarged histiocytic cells with granular cytoplasm. Magnetic resonance imaging showed liver enlargement, changes in the femoral heads without osteonecrosis, a pathological fracture of the third thoracic vertebrae (T3), with absence of brain and spinal cord neurological abnormalities. The biochemical investigation disclosed low levels of β-glucocerebrosidase (0.223 nmol/h/ml; normal: above 0.98) and increased levels of lyso-Gb1 (0.43 µg/ml; normal: up to 0.003). Genotyping of the GBA1 gene indicated the presence of the pathogenic variant p.Arg87Trp (R48W) in homozygosis. Discussion and Conclusion: To the best of our knowledge, this report describes the first case of GD type 1 confirmed via biochemical and molecular genetic testing in Mozambique. As awareness of the GD and rare genetic diseases among Mozambican health professionals is very limited, and resources for diagnosis are scarce in the national health system, it is possible that other cases remain undiagnosed in this low-income country.

Acetylcholinesterase Levels in Farmers Exposed to Pesticides in Malaysia.

Agriculture is an important component of the Malaysian economy. Pesticides are widely used by farmers to increase crop production. Acetylcholinesterase (AChE) is known to play an important role in the degradation of acetylcholine (ACh) at the neuromuscular junction of the nervous system. The purpose of this study was to determine the effect of pesticide exposure on serum levels of AChE of farmers. A cross-sectional study was conducted. A total of 95 farmers from Kelantan (n = 49) and Selangor (n = 46) aged between 23 and 71 years were recruited. AChE concentration was measured by spectrophotometry. The results of this study showed that the mean AChE concentrations in farmers from Kelantan and Selangor were 2,715 and 2,660 U/L, respectively, significantly different (p < 0.05) from normal reference value (3500 U/l). Pearson correlation test showed a moderate correlation between AChE level and age (r = - 0.551) and a strong correlation between AChE level and working period (r = -0.872) in farmers in Kelantan. AChE levels in Selangor were also moderately correlated with age (r = -0.353) and working period (r = -0.515). In conclusion, increasing age and long-term pesticide exposure reduce AChE levels in farmers.

Candidate genes prediction in pakistani families with hearing impairment by using bioinformatic approach / Predição de genes candidatos em famílias paquistanesas com deficiência auditiva utilizando uma abordagem de bioinformática

Multiple factors such as genetic and environmental, are involved in causing hearing impairment (HI). Severe or profound hearing loss affects approximately one in 1000 children worldwide and half of these cases are due to genetic factors. In case of hereditary nonsyndromic HI, approximately 75­80% of cases are involved in autosomal recessive inheritance and 15% of cases involve autosomal dominant inheritance. HI represents extreme genetic heterogeneity. In nonsyndromic deafness, 135 loci have been mapped till now including 77 autosomal recessive genes of which only 29 corresponding nuclear genes have been cloned. This study was designed to apply bioinformatic approach for reducing large number of candidate genes responsible for deafness to a handy number for their mutation analysis. Databases of expressed mouse inner ear genes and the expressed human cochlear genes were used to cross-reference all genes present in particular locus predicting candidate genes for phenotypes of nonsyndromic hereditary HI. These candidate genes are a source of starting point for mutation analysis along with genetic linkage to refine the loci. After characterization, it was observed that KIAA119 and EDN3 are candidate genes for deafness. In present study, there were total 14 loci and two genes KIAA119 and EDN3 were identified as candidate genes in locus 48 and locus 65 respectively. If mutation analysis of the two characterized genes is done, it will not be a comparatively time taking and labor-intensive process as these genes are only two in number.

Diversos fatores, tais como genéticos e ambientais, estão envolvidos na causa da deficiência auditiva (HI). A perda auditiva severa ou profunda afeta aproximadamente uma em cada 1000 crianças em todo o mundo e metade destes casos são devidos a fatores genéticos. Em relação a HI não-sindrômica hereditária, cerca de 75-80% dos casos estão envolvidos na herança autossômica recessiva e 15% dos casos envolvem herança autossômica dominante. HI representa extrema heterogeneidade genética. Em casos de surdez, 135 loci foram mapeados até agora, incluindo 77 genes autossômicos recessivos das quais apenas 29 genes correspondentes nucleares foram clonados. Este estudo foi desenhado para aplicar abordagem de bioinformática a fim de reduzir o grande número de genes candidatos responsáveis pela surdez a um número útil para a análise de mutação. Bases de dados de genes expressos do ouvido interno em camundongos e de genes expressos na cóclea em humanos foram usados para cruzar todos os genes presentes no locus específico prevendo genes candidatos para os fenótipos de HI não sindrômica hereditária. Estes genes candidatos são uma fonte de ponto de partida para a análise de mutação, juntamente com a ligação gênica para refinar os locos. Após a caracterização, verificouse que KIAA119 e EDN3 são genes candidatos para a surdez. No presente estudo, houve um total de 14 locos e dois genes KIAA119 e EDN3 foram identificados como genes candidatos no locus 48 e locus 65, respectivamente. Se a análise de mutação dos dois genes caracterizados for feita, não será um processo comparativamente longo e trabalhoso uma vez que são apenas dois genes.