Abstract
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by the deletion or mutation of the survival motor neuron 1 (SMN1) gene. The establishment of effective newborn screening (NBS) for SMA is important for early diagnosis so that treatment can be administered in the pre-symptomatic or early disease stages. Polymerase chain reaction (PCR)-based genetic testing with dried blood spots has been used in NBS to detect the homozygous deletion of exon 7 in SMN1, however, this methodology is not able to detect newborn infants with heterozygous deletions and/or point mutations in SMN1. We report the case of a male infant who was diagnosed with SMA despite the NBS being negative for all conditions including SMA. The patient presented with severe hypotonia and muscle weakness from around 14 days of age. SMA was suspected and sequence analysis of SMN1 and SMN2 was conducted using the multiplex ligation-dependent probe amplification (MLPA) method, which revealed compound heterozygous mutations of SMN1. The patient was diagnosed with SMA and started on modulating agents including gene therapy. His motor function improved slightly with treatment, however, his motor development remained prominently retarded by 5 months of age. This case highlights the importance of investigating SMA as a potential diagnosis even when the NBS result is negative.