EC Paediatrics

Introduction: Spinal muscular atrophy (SMA) is a genetic disease with homozygous deletion or mutation of the SMN1 motor neuron survival gene. Incidence is 1 in 10,000 births. Clinical manifestations include variable progressive muscle weakness, respiratory and bulbar muscle involvement, respiratory failure, dependence on noninvasive ventilation (NIV) or tracheostomy tubes (TQ) with normal cognitive development; about 50% are SMA type 1. In 2017, specific molecules emerged that increase SMN protein through messenger RNA splicing modifications or gene therapy, improving motor function. Data on respiratory outcomes are limited, the main cause of premature death or morbidity.

Objective: To describe the ongoing respiratory status of children with SMA1 treated with specific therapies at a national referral center in Chile.

Method: Prospective cohort of SMA1 patients treated at the neuromuscular disease program at Clinica Las Condes, Santiago, Chile 2017 to 2022. A respiratory care guideline for ventilatory failure prevention was developed, with early noninvasive ventilatory support (NIVS), high IPAPs (14 to 18) and low EPAPs (3-4), differential 10-15, nasal interface, plus pulmonary recruitment with cough assistance equipment and/or ambu bag. Approved by Institution Ethics Committee 2017. Respiratory support and complications were recorded until 2024.

Results: Thirty-three SMA1 patients receiving treatment were recruited: nursinersen 28, risdiplam 4, gene therapy 8, and combination therapy 7. The median age at diagnosis was 2 months (0-10), and the median current age is 36 months (4-94); 48% (16/33) were admitted with TQ for follow-up and are still on it, one patient died. 18 patients were admitted without TQ, started with early NIVS; one on presymptomatic treatment never used NIVS: 50% (9/18) with NIVS achieved sitting position and 2 were able to walk. Four patients were intubated, one of them was successfully extubated on 3 occasions. Children without TQ use NIV at night and during respiratory infections. Twenty-seven hospitalizations were recorded in 11 patients; 2 patients have chronic atelectasis at start of protocol. None develop chronic atelectasis during protocol follow up.

Conclusion: Despite specific therapies improved motor function, patients with TQ at the beginning of the study are still on it. Patients without TQ at baseline have been unable to discontinue NIVS, but they require same o less support, with shorter hospitalizations and complications. Starting specific therapies presymptomatic o very early in the course of the diseases have better motor and respiratory outcomes, however NIVS is crucial to have less respiratory complications and medical resource utilization.

 Keywords. Spinal Muscular Atrophy; Respiratory Care; Non-Invasive Ventilation; Non-Invasive Ventilatory Support; Nursinersen; Risdiplam; Gene Therapy; Onasemnogene Abeparvovec

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