Author/Authors :
Hashemian, Somayyeh Department of Pediatric Endocrinology and Metabolism - Akbar Hospital - Mashhad University of Medical Sciences, Mashhad , Eshraghi, Peyman Department of Pediatric Endocrinology and Metabolism - Akbar Hospital - Mashhad University of Medical Sciences, Mashhad , Dilaver, Nafi Swansea University College of Medicine - Swansea University - Swansea, UK , Galehdari, Hamid Narges Medical Genetics and Prenatal Diagnosis Laboratory - East Mihan Ave - Kianpars, Ahvaz , Shalbafan, Bita Iran Social Security Organization - Labafinejad Hospital, Tehran , Vakili, Rahim Medical Genetic Research Center - Mashhad University of Medical Sciences, Mashhad - Department of Molecular Genetics - Hope Generation Genetic Polyclinic, Mashhad , Ghaemi, Nosrat Department of Pediatric Endocrinology and Metabolism - Akbar Hospital - Mashhad University of Medical Sciences, Mashhad , Ahangari, Najmeh Department of Molecular Genetics - Hope Generation Genetic Polyclinic, Mashhad , Rezazadeh, Jamileh Genetic counselling and Rehabilitation Unit - Welfare organization, South Khorasan , Varaghchi, Jamileh Rezazadeh Genetic counselling and Rehabilitation Unit - Welfare organization, South Khorasan , Zeighami, Jawaher Narges Medical Genetics and Prenatal Diagnosis Laboratory - East Mihan Ave - Kianpars, Ahvaz , Sedaghat, Alireza Department of Internal Medicine - Ahvaz Jundishapur University of Medical Sciences, Ahvaz , Aminzadeh, Majid Department of Pediatrics - Ahvaz Jundishapur University of Medical Sciences, Ahvaz , Hamid, Mohammad Department of Molecular Medicine - Biotechnology Research Center - Pasteur Institute of Iran, Tehran , Saberi, Alihossein Department of Medical Genetics - Ahvaz Jundishapur University of Medical Sciences, Ahvaz , Ashtari, Fereshteh Department of Neurology - School of Medicine - Isfahan University of Medical Science, Isfahan , Ghayoor Karimiani, Ehsan Razavi Cancer Research Center - Razavi Hospital - Imam Reza International University, Mashhad - Division of Evolution and Genomic Sciences - Medicine and Health Sciences - University of Manchester, UK , Shariati, Gholamreza Narges Medical Genetics and Prenatal Diagnosis Laboratory - East Mihan Ave - Kianpars, Ahvaz
Abstract :
Objectives: Niemann-Pick diseases (NPD) is an autosomal recessive
inherited lysosomal lipid storage disorder which occurs due to a defect
in cellular cholesterol trafficking, leading to excess lipid accumulation
in multiple organ systems such as the brain, lungs, spleen, and liver.
SPMD1-associated disease includes classic infantile and visceral
NPD type A and B respectively. Type C NPD is subacute or juvenile.
Materials & Methods
During 2012-2016, the patients who had the clinical and biochemical
signs and symptoms of different types of NPD, underwent genetic
analysis. All patients were collected from five provinces in Iran
(Razavi Khorasan, South Khorasan, Khozaestan, Isfahan and Tehran
province). Sanger sequencing of the candidate genes for NPD was
performed followed by bioinformatics analysis to confirm the types
of NPD and to identify novel mutations. All patients underwent full clinical assessment.
Results: We present two cases with NPD type A, six cases with NPD
type B, and 11 cases with type C with various enzymatic defects
identified in these cases. Within these 19 patients, we present 9
previously reported mutations and 10 novel mutations causing NPD.
Conclusion: This study is the largest Iranian study for NPD analysis
ever. Our report demonstrates that NPD has a variable age of onset
and can present early in life. We investigated the clinical and genetic
manifestations of a large Iranian cohort. Understanding the variable presentation of NPD will allow for clinicians to have a high
index of suspicion for the disease.
