Novel gene-specific Bayesian Gaussian mixture model to predict the missense variants pathogenicity of Sanfilippo syndrome.

MPS III is an autosomal recessive lysosomal storage disease caused mainly by missense variants in the NAGLU, GNS, HGSNAT, and SGSH genes. The pathogenicity interpretation of missense variants is still challenging. We aimed to develop unsupervised clustering-based pathogenicity predictor scores using extracted features from eight in silico predictors to predict the impact of novel missense variants of Sanfilippo syndrome.

Biochemical diagnosis of Sanfilippo disorder types A and B.

Background: One of the 11 recognized mucopolysaccharidosis (MPS) diseases is Sanfilippo. It is autosomal recessive in its mode of transmission. There are four subtypes of Sanfilippo (A, B, C, and D).

Profile of plasma free amino acids, carnitine and acylcarnitines, and JAK2 mutation as potential metabolic markers in children with type 1 diabetic nephropathy.

Fifty diabetic nephropathy (DN) children with type 1 diabetes mellitus (T1DM) and 50 healthy matched controls were included. Chromatographic assays of 14 amino acids, free carnitine and 27 carnitine esters using high-performance liquid chromatography/electrospray ionization-mass spectroscopy, and genetic testing for JAK2 mutation using real-time PCR were performed. Patients had significantly lower levels of tyrosine, branched-chain amino acids (BCAAs), and BCAA/AAA (aromatic chain amino acids) ratios, glycine, arginine, ornithine, free carnitine and some carnitine esters (C5, 6, 12 and 16) and higher phenylalanine, phenylalanine/tyrosine ratio and C18 compared with the controls and in the macro-albuminuria vs.

Biochemical and mutational analyses of HEXA in a cohort of Egyptian patients with infantile Tay-Sachs disease. Expansion of the mutation spectrum.

Background: Tay-Sachs disease (TSD), an autosomal recessively inherited neurodegenerative lysosomal storage disease, reported worldwide with a high incidence among population of Eastern European and Ashkenazi Jewish descent. Mutations in the alpha subunit of HEXA that encodes for the β-hexosaminidase-A lead to deficient enzyme activity and TSD phenotype. This study is the first to highlight the HEXA sequence variations spectrum in a cohort of Egyptian patients with infantile TSD.

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.

Quaternary diagnostics scheme for mucolipidosis II and detection of novel mutation in GNPTAB gene.

Background: Mucolipidosis II (ML II α/β) is an inherited lysosomal storage disorder caused by deficiency of GlcNAc-phosphotransferase enzyme and results in mis-targeting of multiple lysosomal enzymes. Affected patients are characterized by skeletal deformities and developmental delay. Homozygous or compound heterozygous mutations in GNPTAB gene are associated with the clinical presentation.

Clinical, Biochemical, and Molecular Characterization of Metachromatic Leukodystrophy Among Egyptian Pediatric Patients: Expansion of the ARSA Mutational Spectrum.

Metachromatic leukodystrophy (MLD) is a neurodegenerative disorder characterized by progressive demyelination due to deficiency of the enzyme arylsulfatase A (ARSA) in leukocytes, and consequently leads to impaired degradation and accumulation of cerebroside-3-sulfate (sulfatide). This study aimed to sequence the ARSA gene in a total of 43 patients with metachromatic leukodystrophy descendant from 40 Egyptian families. In addition, four carrier parents from two families with children who had died from MLD came to the clinic for genetic analysis.

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 β-glucosidase activity, with consequent accumulation of glucocerebroside. Less than 15% of mean normal acid β-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.

A multicenter, open-label, phase III study of Abcertin in Gaucher disease.

Background: Gaucher disease (GD) is caused by a deficiency in the lysosomal enzyme glucocerebrosidase. Enzyme replacement therapy (ERT) is recommended for clinical improvement.

Methods: The efficacy and safety of a new imiglucerase, Abcertin, were assessed in 7 Egyptian patients with treatment-naïve type 1 GD.

Four novel mutations in the N-acetylgalactosamine-6-sulfate sulfatase gene among Egyptian patients with Morquio A disease.

Morquio A disease (Mucopolysaccharidosis IVA, MPS IVA) is an autosomal recessive lysosomal storage disorder caused by deficient activity of the enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS) encoded by the GALNS gene. This deficiency leads to a decreased ability to degrade the glycosaminoglycans (GAGs) keratan sulfate and chondroitin 6-sulfate, thereby causing their accumulation within the lysosomes and consequently prominent skeletal and visceral abnormalities. Clinical evaluation and biochemical GALNS enzyme activity determination were carried out for the patients from four unrelated Egyptian families.

PEX6 is Expressed in Photoreceptor Cilia and Mutated in Deafblindness with Enamel Dysplasia and Microcephaly.

Deafblindness is part of several genetic disorders. We investigated a consanguineous Egyptian family with two siblings affected by congenital hearing loss and retinal degeneration, initially diagnosed as Usher syndrome type 1. At teenage, severe enamel dysplasia, developmental delay, and microcephaly became apparent.

Glycogen storage disease type III in Egyptian children: a single centre clinico-laboratory study.

Background And Study Aims: Glycogen storage disease type III (GSD III) is an autosomal recessive disorder caused by deficiency of glycogen debrancher enzyme and is characterised by clinical variability.

Patients And Methods: We herein describe the clinical and laboratory findings in 31 Egyptian patients with GSD III presenting to the Paediatric Hepatology Unit, Cairo University, Egypt.

Results: Eighteen patients (58%) were males.

Mutational Analysis of the alpha-L-iduronidase gene in three Egyptian families: identification of three novel mutations and five novel polymorphisms.

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disorder that results from a deficiency in alpha-L-iduronidase (IDUA), which is involved in the degradation of dermatan and heparan sulfates. MPS I has three clinical phenotypes, ranging from the severe Hurler form to the milder Scheie phenotype. In this study, mutational analysis of the IDUA gene in three unrelated Egyptian families with Hurler phenotype was performed by sequencing the IDUA exons and exon-intron boundaries.

Dyggve-Melchior-Clausen syndrome: clinical, genetic, and radiological study of 15 Egyptian patients from nine unrelated families.

Introduction: Dyggve-Melchior-Clausen (DMC) syndrome is a rare autosomal recessive type of skeletal dysplasia. It is characterized by the association of progressive spondyloepimetaphyseal dysplasia (SEMD), microcephaly, mental retardation (MR), and coarse facies. The radiographic appearance of generalized platyspondyly with double-humped end plates and the lace-like appearance of iliac crests are pathognomonic and distinctive of DMC syndrome.

Egyptian glycogen storage disease type III - identification of six novel AGL mutations, including a large 1.5 kb deletion and a missense mutation p.L620P with subtype IIId.

Background: Glycogen storage disease type III (GSD III) is caused by mutations in AGL which encodes for a single protein with two enzyme activities: oligo-1, 4-1, 4-glucantransferase (transferase) and amylo-1, 6-glucosidase. Activity of both enzymes is lost in most patients with GSD III, but in the very rare subtype IIId, transferase activity is deficient. Since the spectrum of AGL mutations is dependent on the ethnic group, we investigated the clinical and molecular characteristics in Egyptian patients with GSD III.

Prenatal diagnosis of perplexing cases of lipidoses.

Objective: To present and discuss the technical, ethical and counseling difficulties that were encountered in the prenatal diagnosis of some perplexing cases of lipidoses.

Patients: Four pregnant women were referred to us for prenatal diagnosis with the diagnosis of lipidosis in an affected sibling.

Discussion: (1) It is recommended to do the enzyme assays as the first choice in all cases suspected clinically to have lipidoses in order to establish the diagnosis instead of doing invasive procedures as liver and bone marrow biopsies.

Clinical spectrum associated with some structural cerebellar abnormalities.

Objective: To review the clinical, neuroimaging, cytogenetic, and biochemical studies obtained in 20 patients with different cerebellar structural abnormalities presenting at variable ages of onset with variable signs and symptoms.

Methods: These patients visited the Clinical Genetics Department, National Research Center, Cairo, Egypt during the period from September 2002 to September 2003. All patients were subjected to complete personal and family history taking 3 generation family pedigree construction and full clinical examination, including complete eye evaluation.

Molecular characterization of Egyptian patients with glycogen storage disease type IIIa.

Glycogen storage disease type IIIa (GSD IIIa) is an autosomal recessive disorder characterized by excessive accumulation of abnormal glycogen in the liver and muscles and caused by a deficiency in the glycogen debranching enzyme. The spectrum of AGL mutations in GSD IIIa patients depends on ethnic group-prevalent mutations have been reported in the North African Jewish population and in an isolate such as the Faroe islands, because of the founder effect, whereas heterogeneous mutations are responsible for the pathogenesis in Japanese patients. To shed light on molecular characteristics in Egypt, where high rate of consanguinity and large family size increase the frequency of recessive genetic diseases, we have examined three unrelated patients from the same area in Egypt.