The First Report of Iranian Registry of Patients with Spinal Muscular Atrophy

Article type: Research Article

Authors: Mansouri, Vahid^{a; †; 1} | Heidari, Morteza^{b; †; 2} | Bemanalizadeh, Maryam^{b; c; 3} | Azizimalamiri, Reza^d | Nafissi, Shahriar^e | Akbari, Masood Ghahvechi^f | Barzegar, Mohammad^g | Moayedi, Ali Reza^h | Badv, Reza Shervin^b | Mohamadi, Mahmood^b | Tavasoli, Ali Reza^b | Amirsalari, Susanⁱ | Khajeh, Ali^j | Inaloo, Soroor^k | Fatehi, Farzad^e | Hosseinpour, Sareh^l | Babaei, Meisam^m | Hosseini, Seyed Ahmadⁿ | Mahdi Hosseiny, Seyyed Mohammad^o | Fayyazi, Afshin^o | Hosseini, Firoozeh^o | Toosi, Mehran Beiraghi^p | Khosroshahi, Nahid^q | Ghabeli, Homa^b | Biglari, Habibeh Nejad^r | Kakhki, Simin Khayatzadeh^q | Mirlohi, Seyed Hossein^s | Bidabadi, Elham^t | Mohammadi, Bahram^u | Omrani, Abdolmajid^v | Sedighi, Mostafa^w | Vafaee-Shahi, Mohammad^x | Rasulinezhad, Maryam^x | Hoseini, Seyyed Mohamad^y | Movahedinia, Mojtaba^z | Rezaei, Zahra^b | Karimi, Parviz^aa | Farshadmoghadam, Hossein^ab | Anvari, Saeed^ac | Yaghini, Omid^c | Nasiri, Jafar^c | Zamani, Gholamreza^{b; *} | Ashrafi, Mahmoud Reza^{b; ad; *}

Affiliations: [a] Gene Therapy Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran | [b] Department of Pediatrics, Division of Pediatric Neurology, Children’s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran | [c] Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran | [d] Department of Pediatric Neurology, Golestan, Medical, Educational, and Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran | [e] Neurology Department, Shariati Hospital, Iranian Neuromuscular Research Center (INMRC), Tehran University of Medical Sciences, Tehran, Iran | [f] Physical Medicine and Rehabilitation Department, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran | [g] Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran | [h] Department of Pediatric Neurology, Children’s Hospital, Hormozgan University of Medical Sciences, Bandar Abbas, Iran | [i] New Hearing Technologies Research Center, Baqiatallah University of Medical Sciences, Tehran, Iran | [j] Department of Pediatrics, Children and Adolescent Health Research Center, Zahedan University of Medical Sciences, Zahedan, Iran | [k] Neonatal Research Center, Shiraz University of Medical Sciences, Shiraz, Iran | [l] Department of Pediatrics, Division of Pediatric Neurology, Vali-e-Asr Hospital, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran | [m] Department of Pediatrics, North Khorasan University of Medical Sciences, Bojnurd, Iran | [n] Department of Pediatrics, Taleghani Children’s Hospital, Golestan University of Medical Sciences, Gorgan, Iran | [o] Department of Pediatric Neurology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran | [p] Department of Pediatric Neurology, Mashhad University of Medical Sciences, Mashhad, Iran | [q] Department of Pediatrics, Division of Pediatric Neurology, Bahrami Hospital, Tehran University of Medical Sciences, Tehran, Iran | [r] Department of Pediatrics, School of Medicine, Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran | [s] Pediatric respiratory and sleep medicine research center, children’s medical center, Tehran University of Medical sciences, Tehran, Iran | [t] Guilan University of Medical Sciences, Rasht, Iran | [u] Department of Pediatrics, Yasuj University of Medical Sciences, Yasuj, Iran | [v] Department of Pediatrics, Faculty of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran | [w] Department of Neurology, Kermanshah University of Medical Sciences, Kermanshah, Iran | [x] Pediatric Neurology Department, Iran University of Medical Sciences, Tehran, Iran | [y] Department of Pediatrics, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran | [z] Department of Pediatrics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran | [aa] Department of Pediatric Diseases, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran | [ab] Department of Pediatrics, Children Growth Research Centre, Research Institute for Prevention of Non-Communicable Disease, Qazvin University of Medical Science, Qazvin, Iran | [ac] Department of Pediatrics, Division of Pediatric Neurology, Milad Hospital, Social Security Organisation, Tehran, Iran | [ad] Pediatric Cell and Gene Therapy Research Center (PCGTRC), Tehran University of Medical Sciences, Tehran, Iran

Correspondence: [*] Correspondence to: Mahmoud Reza Ashrafi, Department of Pediatrics, Division of Pediatric Neurology, Children’s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran. Tel.: +98 1411713135; E-mails: [email protected], [email protected] and Gholamreza Zamani, Department of Pediatrics, Division of Pediatric Neurology, Children’s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran. E-mail: [email protected].

Note: [†] These authors contributed equally to this work.

Note: [1] ORCID: 0000-0002-3726-1496.

Note: [2] ORCID: 0000-0002-7487-569X.

Note: [3] ORCID: 0000-0002-6055-8917.

Abstract: Background:Insufficient amounts of survival motor neuron protein is leading to one of the most disabling neuromuscular diseases, spinal muscular atrophy (SMA). Before the current study, the detailed characteristics of Iranian patients with SMA had not been determined. Objective:To describe the key demographic, clinical, and genetic characteristics of patients with SMA registered in the Iranian Registry of SMA (IRSMA). Methods:IRSMA has been established since 2018, and the demographic, clinical, and genetic characteristics of patients with SMA were recorded according to the methods of treat neuromuscular disease (TREAT-NMD) project. Results:By October 1, 2022, 781 patients with 5q SMA were registered. Of them, 164 patients died, the majority of them had SMA type 1 and died during the first 20 months of life. The median survival of patients with type 1 SMA was 23 months. The consanguinity rate in 617 alive patients was 52.4%, while merely 24.8% of them had a positive family history. The most common type of SMA in live patients was type 3. Morbidities were defined as having scoliosis (44.1%), wheelchair dependency (36.8%), tube feeding (8.1%), and requiring mechanical ventilation (9.9%). Most of the registered patients had a homozygous deletion of SMN1, while the frequency of patients with higher copy numbers of SMN2, was less in more severe types of the disease. Earlier onset of the disease was significantly seen in patients with lower copy numbers of SMN2. The neuronal apoptosis inhibitory protein (NAIP) gene deletion was associated with a higher incidence of more severe types of SMA, higher dependency on ventilators, tube feeding, and earlier onset of the disease. Conclusions:The IRSMA is the first established Iranian nationwide registry of patients with SMA. Using this registry, decision-makers, researchers, and practitioners can precisely understand the epidemiology, characteristics, and genetics of patients with SMA in Iran.

Keywords: Registry, Iran, Spinal muscular atrophy, Neuronal apoptosis inhibitory protein

DOI: 10.3233/JND-221614

Journal: Journal of Neuromuscular Diseases, vol. 10, no. 2, pp. 211-225, 2023