Mucopolysaccharidoses diagnosis in the era of enzyme replacement therapy in Egypt.

BACKGROUND: Undegraded glycosaminoglycans (GAGs) induced by deficiency of enzymes are the primary cause of mucopolyscchardoses. Mucopolysacchardoses (MPS) are a group of rare lysosomal storage diseases (LSD). The quantification of a specific enzymatic activity is needed for accurate diagnosis. The objectives of this work were: first, to continue the study of mucopolysacchardoses disease in Egypt after the start of using the enzyme replacement therapy (ERT). Second, to define the commonest types among our population after 18 years experience with the disease. Third, to compare the different MPS types' distribution, diagnosed after the start of the ERT, to identify the impact of using ERT on the number and type of diagnosed patients. METHOD: Urinary GAGs were measured for all referred cases followed by two-dimensional electrophoretic separation for cases with high levels of GAGs; the specific enzyme activity was assayed for each type depending on the abnormal electrophoretic pattern obtained. Clinically suspected cases of Morquio syndrome were directly subjected to measuring the specific enzyme. RESULTS: Out of 1448 suspected cases, 622 (42.9%) MPS patients were diagnosed revealing the following distribution: MPS I (172, 27.7%), MPS II (57, 9.1%), MPS III [(177, 28.5%: 134 type B and 43 types A, C or D)], MPS IVA (124, 19.9%), MPS VI (90, 14.5%) and MPS VII (2, 0.3%). MPS III was the most commonly diagnosed type followed by MPS I and MPS IVA. MPS IVA represented the most common type receiving treatment, followed by MPS I, MPS II and MPS VI. CONCLUSION: The presence of treatment encouraged the affected families and physicians to seek diagnosis. MPS III was the commonest type among our studied group after 7 years of diagnosis, while MPS IVA was the commonest type receiving treatment.

The potential impact of COMT gene variants on dopamine regulation and phenotypic traits of ASD patients.

Catechol-O-methyltransferase (COMT) enzyme has a major role in the adjustment of catechol-dependent functions, for example, cognition, cardiac function, and pain processing. The pathogenesis of autism may be related to dysfunction in the midbrain dopaminergic system. Therefore, we aimed to clarify how COMT gene variants affect dopamine level, and its potential impact on phenotype traits of autistic patients. 52 autistic patients were subjected to comprehensive clinical investigation, sequencing of exon 4 of the COMT gene by direct Sanger Sequencing, and measuring of dopamine levels. The clinical presentations of autistic subjects were correlated with detected COMT variants and dopamine level. Our molecular results revealed that three COMT variants were found: rs8192488 [C > T], rs4680 (Val158Met) and rs4818 [C > G]. Within autistic subjects, Val158Met rs4680 carriers were significantly distributed (71.2% P = 0.014) accompanied with abnormal dopamine, abnormal Electroencephalogram (EEG) and increasing the severity of autistic behaviour. As regards the haplotypes, CC/VM/CG block was significantly distributed among the autistic subjects (30.8%) presented with low mean dopamine level (15.8 ±â€¯4.7 pg/ml, p = 0.05), while CC/MM/CC were presented with high mean level (77.8 ±â€¯8.6 pg/ml, p = 0.05). Evidence is currently limited and preliminary, further studies are necessary in order to set up a coherent dopaminergic model of Autism Spectrum Disorder (ASD), which would further pave the way for an adequate treatment.

Twenty- five years of biochemical diagnosis of Gaucher disease: the Egyptian experience.

BACKGROUND: Gaucher disease is a rare multi-systemic metabolic disorder resulting from the deficiency of acid ß-glucosidase activity, with consequent accumulation of glucocerebroside. Less than 15% of mean normal acid ß-glucosidase activity in leukocytes is the gold standard for the diagnosis of Gaucher disease, and is generally supplemented by a massive elevation in chitotriosidase activity. We report here our experience in the biochemical diagnosis of Gaucher disease by showing the heterogeneity of the activity of enzymes over 25 years from 1993-2017, through the analysis of 5128 clinically suspected Gaucher disease cases referred to the Biochemical Genetics Department, National Research Centre, as the main reference lab in Egypt for the diagnosis of Inherited Metabolic Disorders. METHODS: Acid ß-glucosidase and chitotriosidase activities were measured in all referred cases. Sphinogmylinase activity was estimated for all cases with normal ß-glucosidase activity and moderate elevation of chitotriosidase. RESULTS: Out of the 5128 suspected cases, 882 (17%) showed a deficiency in acid ß-glucosidase activity, accompanied by a raised chitotriosidase activity, ranges (213-66700 umol/l/h) and mean (7255 umol/l/h). Deficient chitotriosidase activity was found in 9 patients (1%) with low ß-glucosidase. 451 cases were diagnosed with acid sphingomyelinase deficiency patients (8.8%). CONCLUSION: Other biochemical markers are needed in addition to chitotriosidase for the diagnosis and follow up. Molecular testing was done to a relatively small number but needs to be done to all diagnosed patients as many mutations are known to predict the course of the disease.

Effect of natural PAL-enzyme on the quality of egg white and mushroom flour and study its impact on the expression of PKU related genes and phenylalanine reduction in mice fed on.

PKU patients react to therapy with a low phenylalanine diet, but adherence to this diet is troublesome, subsequently the expansion of alternative ways is demand. Phenylalanine ammonia lyase (PAL) is one of this ways, which converts phenylalanine to harmless metabolites; trans-cinnamic acid and ammonia. In the current study, the extraction of PAL enzyme was used to investigate the efficiency for production of functional PKU egg white and mushroom flour with good quality by evaluation of colour characteristics, determination of phenylalanine concentrations and genetic materials expression of PKU related genes and DNA damage. Results indicated that the PAL enzyme treated of egg white and mushroom flour was stable colour and the calculated reduction per cent in phenylalanine concentration from female mice fed on untreated and PAL-treated samples was 22.77% in egg white and 31.37% in mushroom flour. Also, the results revealed that female mice fed on diet contained treated egg white exhibited low expression levels of PKU exons (3, 6, 7, 11, and 12) and low DNA damage which were similar to those in control mice.