Acid ceramidase deficiency is an orphan lysosomal disorder caused by ASAH1 pathogenic variants and presenting with either Farber disease or spinal muscle atrophy with progressive myoclonic epilepsy ...(SMA‐PME). Phenotypic and genotypic features are rarely explored beyond the scope of case reports. Furthermore, the new biomarker C26‐Ceramide requires validation in a clinical setting. We evaluated the clinical, biomarker and genetic spectrum of 15 Egyptian children from 14 unrelated families with biallelic pathogenic variants in ASAH1 (12 Farber and 3 SMA‐PME). Recruited children were nine females/six males ranging in age at diagnosis from 13 to 118 months. We detected ASAH1 pathogenic variants in all 30 alleles including three novel variants (c.1126A>G (p.Thr376Ala), c.1205G>A (p.Arg402Gln), exon‐5‐deletion). Both total C26‐Ceramide and its trans‐ isomer showed 100% sensitivity for the detection of ASAH1‐related disorders in tested patients. A 10‐year‐old girl with the novel variant c.1205G>A (p.Arg402Gln) presented with a new peculiar phenotype of PME without muscle atrophy. We expanded the phenotypic spectrum of ASAH1‐related disorders and validated the biomarker C26‐Ceramide for supporting diagnosis in symptomatic patients.
Pycnodysostosis is a rare autosomal recessive disorder with characteristic diagnostic manifestations. This study aims to phenotype and provide molecular characterization of Egyptian patients, with ...emphasis on identifying unusual phenotypes and raising awareness about pycnodysostosis with different presentations to avoid a mis- or under-diagnosis and consequent mismanagement. We report on 22 Egyptian pycnodysostosis patients, including 9 new participants, all descending from consanguineous families and their ages ranging from 6 to 15 years. In addition, prenatal diagnosis was performed in one family with affected siblings. They all presented with short stature, except for one patient who presented with pancytopenia as her primary complaint. Moreover, 41.2% of patients had sleep apnea, 14% presented with craniosynostosis, and 44.4% had failure of tooth development. Molecular analysis via direct exome sequencing of the cathepsin K gene revealed three novel mutations ((NM_000396.3) c.761_763delCCT, c.864_865delAA, and c.509G>T) as well as two previously reported mutations among nine new cases. The following is our conclusion: This study expands the molecular spectrum of pycnodysostosis by identifying three novel mutations and adds to the clinical and orodental aspects of the disease. The link between the
gene mutations and the failure of tooth development has not been established, and further studies could help to improve our understanding of the molecular pathology.
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 5years and to compare the disease burden in Egypt in the absence of a national screening program for inherited metabolic disorders with other populations.
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.
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 2.5months to 6.6years 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.
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.
•Tandem mass spectrometry is an essential tool for diagnosing IEMs in Egypt.•Metabolic disorders are relatively common in Egyptian children due to consanguinity.•203 children were diagnosed with 17 different IEMs out of 3380 high risk patients.•Aminoacidopathies especially PKU were the most encountered.•Nationwide expanded NBS by MS/MS is highly recommended for application in Egypt.
Purpose: To assess the pattern and frequency of occurrence of ocular anomalies among other genetic disorders in Egypt. Methods: This is a cross-sectional study of 2500 cases presenting with genetic ...disorders. Cases were recruited from the clinical genetics department of the National Research Centre (NRC) over a four-year period between January 2011 and December 2014. Ophthalmological examination of the cases was performed in the pediatric ophthalmology department of Cairo University Hospitals. Results: Out of 2500 cases with congenital disorders, 2.4% suffered one or more ocular anomalies with a male to female ratio of 1.7:1. Consanguinity was reported in 76.7% and family history was positive in 35% of ocular cases. The most common ocular anomalies were congenital cataract, retinal dystrophies, glaucoma, and retinoblastoma in order of frequency. Chromosomal aberrations were detected in two retinoblastoma cases and in one case of charge association with cataract and iris coloboma. A truncating mutation in exon 8 of OCRL1 was reported in a case of Lowe syndrome with cataract. A total of 51.7% of ocular cases were non-isolated (associated with other genetic disorders). Conclusion: In Egypt, ocular genetic disorders are not uncommon among other genetic disorders. Consanguinity is high, suggesting high incidence of autosomal recessive inheritance of genetic disorders with an ocular component. Proper systemic assessment of all cases with ocular anomalies is a necessity due to the high percentage of non-isolated ocular anomalies. Genetic counseling of parents would help in reducing recurrence rates through prenatal diagnosis whenever possible.
The congenital abnormalities of eyes are a major cause of visual impairment throughout the world. Prevention of visual impairment due to congenital and infantile abnormalities of eyes is very ...important. The aim of this study is to evaluate the frequency and types of congenital ocular anomalies among patients with genetic disorders.
This is a retrospective study that was conducted in the National Research Center, Egypt at the Clinical Genetics Department over a 4-year period. Out of 2500 patients attending the outpatient clinics, a total of 61 patients with congenital ocular malformations (2.44%) were included in this study. They underwent clinical and genetic assessments.
Isolated ocular malformations were found in 70.5% while complex ocular anomalies were found in 29.5%. A total of 37.7% of the patients had a known recognizable syndrome, 24.6% of the patients were classified as having metabolic disorders and 37.7% of the patients were classified as having isolated disorders. Chromosomal abnormalities were found in 4.9% of the patients. Congenital cataract was the most frequent feature in syndromic, metabolic, and isolated disorders. Our study elucidates the significance of the early detection of ocular anomalies for appropriate diagnosis of genetic disorders.
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.
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.
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.
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.
Congenital muscular dystrophies (CMD) are a group of heterogeneous inherited autosomal recessive disorders characterized by muscular weakness, hypotonia and contractures. The Merosin Negative CMD ...(MNCMD) is considered to be the most severe form and is usually associated with white matter abnormalities as seen with brain imaging. Merosin is also expressed in the nervous system and its deficiency could affect its development. This article describes the clinical picture, muscle biopsy findings and neuroimaging abnormalities of eight Egyptian Pediatric patients with the clinical presentation of merosin negative congenital muscular dystrophy. The leading clinical presentation in almost all patients was severe hypotonia, muscular weakness and failure to achieve motor developmental milestones, only Case 2 walked at 2years of age. Mentality was normal in most patients with exception of Case 2 in whom scholastic achievement was poor and was associated with behavior abnormality. Serum Creatine kinase ranged from moderate to severe elevation, 536–3563U/L, Electromyography demonstrated a myopathic pattern in all patients. Brain MRI showed extensive demyelination of the cerebral white matter in 6/8 patients with extension to cerebellar demyelination in Case 5. 5/8 patients underwent muscle biopsy for which immunofluorescence staining for merosin demonstrated complete deficiency of laminin α2 in Case 5 & partial deficiency of laminin α2 in Case 2.
This report demonstrates the utility of Immunofluorescence staining as a guide to confirm the diagnosis of MDCMD especially when molecular diagnosis is not available.
Background: The congenital abnormalities of eyes are a major cause of visual impairment throughout the world. Prevention of visual impairment due to congenital and infantile abnormalities of eyes is ...very important. The aim of this study is to evaluate the frequency and types of congenital ocular anomalies among patients with genetic disorders.
Patients and methods: This is a retrospective study that was conducted in the National Research Center, Egypt at the Clinical Genetics Department over a 4-year period. Out of 2500 patients attending the outpatient clinics, a total of 61 patients with congenital ocular malformations (2.44%) were included in this study. They underwent clinical and genetic assessments.
Results and conclusions: Isolated ocular malformations were found in 70.5% while complex ocular anomalies were found in 29.5%. A total of 37.7% of the patients had a known recognizable syndrome, 24.6% of the patients were classified as having metabolic disorders and 37.7% of the patients were classified as having isolated disorders. Chromosomal abnormalities were found in 4.9% of the patients. Congenital cataract was the most frequent feature in syndromic, metabolic, and isolated disorders. Our study elucidates the significance of the early detection of ocular anomalies for appropriate diagnosis of genetic disorders.
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