MD of pediatrics
Cairo University Children Hospital
Assistant consultant at neurometabolic unit,CUCH
Cairo | Egypt
Main Specialties: Pediatrics
Additional Specialties: pediatric neurology &neurometabolic; disorders
Iman Gamal El Din Mahmoud (M.D) is an assistant consultant of pediatrics ,Cairo university . works at the inherited metabolic disorders unit (IMDU)since 2008 , in the centre of social and preventive medicine at Cairo university children hospital (CUCH) ,shared in projects aiming for extended newborn screening for metabolic diseases in Egypt e.g phenylketonuria (PKU) and aminoacidopathies , aminoacidurias , mitochondrial disorders,diagnosis of lysosomal storage diseases ,awareness and early diagnosis of Wolman disease and a multicenter natural history study of Farber disease led by (Enzyvant) as well as interest in research in many neurogenetic ,neuromuscular and neurometabolic disorders .
Participated in the biomarker project for diagnosis of lysosomal storage disorders in collaboration with Rostock University and Centogene lab in Germany and currently starting with the centometabolic panel project with Centogene lab in Germany.
Has more than 20 national and international publications through collaboration with prof. Dr. Joseph Gleeson(Neurology and neurogenetics) at California and Rockfeller universities in U.S.A, Egyptian national research center and our unit in Cairo university Children hospital of which ,some were published in high impact scientific journals as Science and Nature.
Publications and projects of our unit led to the establishment of a national screening program for phenylketonuria in Egypt in 11/2015. She is a member and secretary of the Egyptian metabolic patients friend association , a member of the Egyptian neuropediatric society(ENPS), European pediatric neurology society(EPNS),international child neurology association (ICNA) and middle east metabolic group , orphanet (MEMG), the society for the study of inborn errors of metabolism (SSIEM) , the AAAS(American association for the advancement of science) ,the National association of rare disorders and the Egyptian national society of human genetics . Received international publications awards with certificate of appreciation from Cairo University in the years 2014 , 2015, 2016,2017,2018 and 2019.
Primary Affiliation: Cairo University Children Hospital - Cairo , Egypt
150PubMed Central Citations
Orphanet J Rare Dis 2019 08 27;14(1):209. Epub 2019 Aug 27.
Centogene AG, Am Strande 7, 18057, Rostock, Germany.
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Eur J Hum Genet 2018 03 17;26(3):330-339. Epub 2018 Jan 17.
Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
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Eur J Paediatr Neurol 2016 Sep 30;20(5):714-22. Epub 2016 May 30.
Medical Molecular Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo 12311, Egypt.
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Nature Genetics VOLUME 48 | NUMBER 9 | SEPTEMBER 2016
Genet Med 2016 05 27;18(5):452-8. Epub 2015 Aug 27.
Synageva BioPharma Corp., Lexington, Massachusetts, USA.
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Journal of Medical Screening
Abstract 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, b-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.
THE INDIAN JOURNAL OF PEDIATRICS
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. Keywords Inborn errors of metabolism . Lysosomal storage disorders . Enzymatic diagnosis .Tandemmass spectrometry . Genetic testing . Egyptian children
Nat Genet 2015 May 6;47(5):528-34. Epub 2015 Apr 6.
1] Laboratory for Pediatric Brain Disease, The Rockefeller University, New York, New York, USA.  Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.  New York Genome Center, New York, New York, USA.
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Clin Biochem 2014 Jun 13;47(9):823-8. Epub 2014 Apr 13.
Inherited Metabolic Disease Unit, Cairo University Children Hospital, Cairo, Egypt; Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Egypt.
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Pediatr Neurol 2014 Feb 24;50(2):140-8. Epub 2013 Oct 24.
Stem Cell Research Laboratory, Centre for Advanced Sciences-National Research Centre, Cairo, Egypt; Neurogenetics Laboratory, Weill Cornell Medical College in Qatar, Doha, Qatar; Department of Neurology, Weill Cornell Medical College, New York, New York. Electronic address:
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Science 2014 Jan;343(6170):506-511
Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.
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Abstract: Background : Osteopetrosis type 3 is a rare autosomal recessive disorder characterized by osteopetrosis , renal tubular acidosis (RTA) and cerebral calcifications. prevalence is <1.000000 with Fewer than 100 cases reported worldwide .It is caused by mutations in the CA2 gene (8q22) encoding carbonic anhydrase II enzyme. Clinically, patients present with a triad of mild osteopetrosis,mixed proximal and distal RTA and intracerebral calcifications. Other manifestations include fractures, growth failure and short stature, developmental delay, intellectual deficit, dental anomalies, cranial nerve compression and hearing impairment. Aim : To increase awareness of osteopetrosis type 3 ,a rare disorder which could strongly mimick lysosomal storage disorders as Gaucher disease. Case Report: A female patient , 2 years old , the 3rd child of non consanguineous parents , was born as a full term by uncomplicated vaginal delivery following an uneventful prenatal period. She presented at the neurometabolic clinic at Cairo university children hospital , mainly by global developmental delay ,aneamia ,recurrent infections and heptosplenomegaly as well as recurrent fractures,bony pains, gastrointestinal symptoms and loss of weight . On clinical examination , her weight was on the 5th centile while both head circumference and height were above the 25th centiles . She had pallor , frontal bossing, gum hyperplasia, hepatosplenomegaly and neurological examination was unremarkable except for mild hypotonia in both lower limbs . Chest and cardiac examinations were free . Investigations : CBC revealed aneamia ,once associated with mild thrombocytopenia . Urinary glycosaminoglycans(GAGs) were elevated. Gaucher disease was excluded by negative biomarker,glucocerebrosidase enzyme assay and genetic analysis . Serum acid sphingomyelinase and chitotriosidase were also normal. Bone marrow aspirate examination was normal and bone marrow biopsy showed relatively hypocellular marrow free of abnormal cells . Result: Characteristic skeletal survey features, blood gases showing acidosis and calcifications in brain CT followed by carbonic anhydrase II(CA2) gene sequencing led to detection of a homozygous pathogenic variant c.232+1G>A,affecting the donor splice site of intron 2 and confirmed diagnosis of osteopetrosis type 3. Conclusion: We recommend performing Blood gases and skeletal survey to help in the differential diagnosis of Gaucher disease like phenotype.
Research Journal of Medicine and Medical Sciences, 4(2): 369-385, 2009
Research Journal of Medicine and Medical Sciences
Abs tract: Ba c kground: Organic acid disorders are a group of disorders characterized by the excretion of non-amino organic acids in urine. Expanded newborn s c re ening methods by tandem mas s spectrometry (MS/MS) can detect organic acidemias early in infancy with a better outcome when diagnosed in the first ten days of life. Aim: This study aims at rev iewing the clinical, biochemical and neuroradiological data of patients diagnosed as organic acidemias and to highlight the importance of including organic acidemias in Newborn screening programs using MS/MS. Methods: Eight hundred p a t ients attending the neurometabolic clinic at Cairo Un iv e rsity Children Hospital (CUCH) screened for inborn errors of metabolism (IEM) by MS/MS. Organic acid pro file in urine, by gas chromatography mas s spectrometry (GC-MS/MS), was performed for selected cases . Results : Nineteen patie n t s out the 800 cases were diagnosed as organic acidemias (1/42).Three cas e s (15.8%) were diagnosed as methyl malonic acidemias (MMA), 3 (15.8%) as â-ketothiolase deficiency (BKT), 2 (10.5%) as 3-me t h y lcrotonylglycinuria (MCG), 3 (15.8%%)as biotinidase deficiency , 2 (10.5%) as Canavan disease, one patient (5.3%)for each of the following: glutaric aciduria type I, D-2 hydroxyglutaric a c id u ria ,is o v a le ric a c id u ria (IVA), asargininosuccinic aciduria (ASA),3-methyl glutaconic aciduria and propionic ac id emia (PA ). Developmental delay was a dominant symptom being pres ent in 16/19 (84.2%) followed by metabolic acidos is in 15/19(78.9% ), vomit in g in 12(63.2%), encephalopathy with dis turbed conscious level in 11 (57.8%), seizures in 8 (42%), overwhelming illness [encephalopathy, re s p ira tory distress, seizures, septicemia, persistent vomitings] in 8 (42%) namely in MMA, PA and BKT and diarrhea in 6(31%)cases. Central nervous system abnormalit ie s in c luding cranial nerve affection in 8(42%) extrapyramidal man ifestations namely dystonia in 4 (21%), ataxia in 2(10.5%), long tract signs in 7(36.8%), h y p o to n ia in 11 (57.8%) patients and dysmorphism in 11 cas es ( 57.8%). Conclus ion: Screening for organic acidopathies by MS/MS using dried blood spot technique is a rapid and efficient method in detecting cases with suspected organic acidemias, requiring confirmatory tests by GC-MS. Including organic acidopathies in newborn sc re en in g wo u ld help in rapid and properly timed therapeutic intervention to prevent devas tating neurological outcomes . However, confirmatory tes ts by GC-MS are mandatory particularly for clinically suspected cas es with normal acyl carnitine profile Key words: Organic acidemia, methylmalonic acidemia, tandem mas s spectrometry
The Egyptian Journal of Medical Human Genetics (2012) 13, 351–357
The Egyptian Journal of Medical Human Genetics
Abstract The mitochondrial DNA depletion syndromes are autosomal recessive disorders characterized by decreased mitochondrial DNA copy number in affected tissues.Mutations in 2 genes involved in deoxyribonucleotide metabolism, the deoxyguanosine kinase gene and the thymidine kinase 2 gene, had been related to this syndrome. This study aims to describe the clinical, histochemical, biochemical and molecular diagnosis of one Egyptian pediatric patient with the myopathic form of mitochondrial depletion syndrome. The patient presented to Cairo University Pediatric Hospital with the clinical suspicion of mitochondrial encephalomyopathy.Histochemical and biochemical studies of the respiratory chain complexes were performed on the muscle biopsy specimen from the patient.Molecular diagnosis was done by quantitative radioactive Southern blot and sequencing analysis of the whole coding regions of the TK2 gene. Histochemical staining revealed cytochrome oxidase negative fibers and increased staining for succinate dehydrogenase. The activity of complex I was not detected and complex IV activity was about 46%of age matched controls. Southern blot analysis showed reduction of the mitochondrial/ nuclear DNA ratio, the degree of depletion was around 30% of aged-matched controls. Sequencing analysis of the TK2 gene revealed no sequence variation. Targeted molecular diagnosis based on the biochemical analysis of the respiratory chain enzymes makes the molecular evaluation of mitochondrial disorders much easier. Involvement of other nuclear genes rather than TK2 gene in the pathogenesis of the myopathic form of mitochondrial depletion syndrome should be considered. 2012 Ain Shams University. Production and hosting by Elsevier B.V. All rights reserved.
ANN NEUROL 2016;80:59–70
Objective: A study was undertaken to characterize the clinical features of the newly described hypomyelinating leu- kodystrophy type 10 with microcephaly. This is an autosomal recessive disorder mapped to chromosome 1q42.12 due to mutations in the PYCR2 gene, encoding an enzyme involved in proline synthesis in mitochondria. Methods: From several international clinics, 11 consanguineous families were identified with PYCR2 mutations by whole exome or targeted sequencing, with detailed clinical and radiological phenotyping. Selective mutations from patients were tested for effect on protein function. Results: The characteristic clinical presentation of patients with PYCR2 mutations included failure to thrive, microce- phaly, craniofacial dysmorphism, progressive psychomotor disability, hyperkinetic movements, and axial hypotonia with variable appendicular spasticity. Patients did not survive beyond the first decade of life. Brain magnetic reso- nance imaging showed global brain atrophy and white matter T2 hyperintensities. Routine serum metabolic profiles were unremarkable. Both nonsense and missense mutations were identified, which impaired protein multimerization. Interpretation: PYCR2-related syndrome represents a clinically recognizable condition in which PYCR2 mutations lead to protein dysfunction, not detectable on routine biochemical assessments. Mutations predict a poor outcome, probably as a result of impaired mitochondrial function.
Journal of Genetic Engineering and Biotechnology (2013) 11, 61–68
Journal of Genetic Engineering and Biotechnology
Abstract 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 2 years 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, 536–3563 U/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 a2 in Case 5 & partial deficiency of laminin a2 in Case 2.