Inborn errors of metabolism detectable by tandem mass spectrometry in Egypt: The first newborn screening pilot study.

OBJECTIVES: To estimate the burden of metabolic disorders detectable by tandem mass spectrometry in Egypt, through a pilot expanded newborn screening programme at Cairo University Children's Hospital in 2008, and examining the results of 3,900 clinically at-risk children, investigated at Cairo University Children's Hospital for the same disorders over the past 7 years using the same technology. METHODS: Dried blood spots of 25,276 healthy newborns from three governorates in Upper, Middle, and Lower Egypt were screened, to give a representative sample of the Egyptian newborn population. Based on the pilot study outcomes and the results of clinically suspected children, we estimated the total birth prevalence of tandem mass spectrometry detectable metabolic disorders, and the relative frequency of several individual disorders. RESULTS: Among the healthy newborns, 13 metabolic disorder cases (five phenylketonuria [1:5,000], two methylmalonic acidemia, and isovaleric acidemia [1:12,500], one each of maple syrup urine disease, propionic acidemia, ß-ketothiolase deficiency, and primary carnitine deficiency [1:25,000]) were confirmed, giving a total birth prevalence of 1:1944 live births. Among the clinically suspected children, 235 cases were diagnosed, representing a much wider disease spectrum. CONCLUSIONS: Egypt has one of the highest reported birth prevalence rates for metabolic disorders detectable by tandem mass spectrometry. Early diagnosis and management are crucial for the survival and well-being of affected children. A nationwide NBS programme by tandem mass spectrometry is recommended.

Lysosomal Storage Disorders in Egyptian Children.

OBJECTIVE: To describe the spectrum, relative prevalence and molecular background of lysosomal storage disorders in Egypt. METHODS: The authors evaluated the selective screening program for the diagnosis of lysosomal storage disorders in Egyptian children presenting to the inherited metabolic disease unit at Cairo University Children's Hospital, the largest tertiary care pediatric hospital in Egypt, over a six-year period (April 2008 through April 2014). During this period, 1,065 suspected children were assessed clinically, biochemically and some genetically. RESULTS: Two hundred and eleven children (aged 44 ± 32 mo; 56 % boys, 82 % with consanguineous parents) were confirmed with 21 different lysosomal disorders. The diagnostic gap ranged between 2 mo and 14 y (average 25 mo). Mucopolysaccharidoses were the most common group of diseases diagnosed (44.5 %), while Maroteaux-Lamy, Gaucher and nephropathic cystinosis were the most commonly detected syndromes (17.1, 14.7 and 13.7 %, respectively). Eighty mutant alleles and 17 pathogenic mutations were detected in 48 genetically assessed confirmed patients (30 Gaucher, 16 cystinosis and two Niemann-Pick type C patients). CONCLUSIONS: This report is the first to describe relative frequency and spectrum of clinical and molecular data in a large cohort of Egyptian lysosomal patients. The crude estimate denotes that over 80 % of Egyptian lysosomal patients do not have access to optimal diagnosis. Upgrading diagnostic and genetic services for lysosomal storage disorders in Egypt is absolutely necessary.

Selective screening for inborn errors of metabolism by tandem mass spectrometry in Egyptian children: a 5 year report.

OBJECTIVE: In order to enhance awareness and promote registry for inborn errors of metabolism (IEMs) in Egypt, we aimed to evaluate the prevalence and main clinical findings of IEMs detectable by tandem mass spectrometry (MS/MS) among high risk pediatric patients presenting to our tertiary care facility at Cairo University Children's Hospital over a period of 5 years and to compare the disease burden in Egypt in the absence of a national screening program for inherited metabolic disorders with other populations. METHODS: During this period 3380 Egyptian children were suspected of having IEMs based on clinical/laboratory presentation and were analyzed by MS/MS. Confirmatory testing was performed according to flagged analyte by MS/MS using a different sample type such as plasma or urine or by a different technique such as GC/MS. RESULTS: A relatively high number of patients (203/3380 (6%)) were confirmed with 17 different types of IEMs. Averages for age at diagnosis for different disorders ranged from 2.5 months to 6.6 years with general developmental delay and irreversible neurological damage being the most common presenting features (75.9% and 65.5%, respectively). Amino acid disorders (127/203 (62.6%)), mainly phenylketonuria (100/203 (49.3%)), were the most encountered, followed by organic acidemias (69/203 (34%)), while fatty acid oxidation defects (7/203 (3.4%)) were relatively rare. 88% of patients were born to consanguineous parents. CONCLUSIONS: The development of a nationwide screening program for IEMs is mandatory for early detection of these potentially treatable disorders, prompt and properly timed therapeutic intervention and prevention of the devastating neurological outcomes.

Evidence of oxidative stress in peroxisomal disorders.

INTRODUCTION: Peroxisomal disorders are subdivided into peroxisome biogenesis disorders (PBDs) and single peroxisomal enzyme deficiency. Many peroxisomal diseases exhibit excessive oxidative stress, leading to neurological alterations and dysfunction. Peroxisomes use oxygen in oxidative reactions that generate hydrogen peroxide. This study aimed to investigate various oxidative stress parameters in patients suffering from peroxisomal disorders. METHODS: A total of 20 patients with peroxisomal disorders, aged six months to 13 years (mean age 5.9 ± 3.2 years), were compared to 14 healthy controls. All individuals were subjected to full history-taking, including a three-generation pedigree analysis concerning parental consanguinity and similarly affected members in the family, with meticulous clinical examination to detect any malformation or anomaly. Estimation of very-long-chain fatty acids and phytanic acid was done to verify the diagnosis. Brain magnetic resonance imaging, electroencephalogram, visual evoked potential, auditory potential and plain radiography were conducted to assess the pathological condition of the patients. Oxidative stress parameters, including nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD), were estimated in both the patients and controls. RESULTS: Significant increases in both MDA and NO were found in patients with PBDs. It was also demonstrated that SOD was significantly lower in patients with PDB than the controls. CONCLUSION: This study sheds more light on the link between oxidative stress and peroxisomal disorders, as oxidative stress may be a hallmark of peroxisomal disorders. Consequently, one of the useful neuronal rescue strategies could be treatment with antioxidant agents in addition to other lines of treatments.

A scoring system for the assessment of clinical severity in osteogenesis imperfecta.

INTRODUCTION: Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility and fractures. Patients with OI have clinical features that may range from mild symptoms to severe bone deformities and neonatal lethality. Numerous approaches for the classification of OI have been published. The Sillence classification is the most commonly used. In this study, we aimed at developing a more refined sub-classification by applying a proposed scoring system for the quantitative assessment of clinical severity in different types of OI. SUBJECTS AND METHODS: This study included 43 patients with OI. Clinical examination and radiological studies were conducted for all patients. Cases were classified according to the Sillence classification into types I-IV. The proposed scoring system included five major criteria of high clinical value: number of fractures per year, motor milestones, long bone deformities, length/height standard deviation score (SDS), and bone mineral density (BMD). Each criterion was assigned a score from 1 to 4, and each patient was marked on a scale from 1 to 20 according to these five criteria. RESULTS: Applying the proposed clinical scoring system showed that all 11 patients with Sillence type I (100%) had a score between 6 and 10, denoting mild affection. The only patient with Sillence type II had a score of 19, denoting severe affection. In Sillence type III, 7 patients (31.8%) were moderately affected and 15 patients (68.2%) were severely affected. Almost all patients with Sillence type IV (88.9%) were moderately affected. CONCLUSIONS: Applying the proposed scoring system can quantitatively reflect the degree of clinical severity in OI patients and can be used in complement with the Sillence classification and molecular studies.