Yasuhiro Takeshima

Newborn screening (NBS) for spinal muscular atrophy (SMA) is necessary, as favorable outcomes can be achieved by treatment with disease-modifying drugs in early infancy. Although SMA-NBS has been initiated in Japan, its clinical results have not been fully reported. We report the findings of the initial 2.5 years of a pilot SMA-NBS of approximately 16,000 infants conducted from February 2021 in Hyogo Prefecture, Japan. Clinical data of 17 infants who tested positive were retrospectively obtained from the NBS follow-up centers participating in this multicenter cohort observational study. Genetic testing revealed 14 false positives, and three infants were diagnosed with SMA. Case 1 had two copies of survival motor neuron (SMN) 2 and showed SMA-related symptoms at diagnosis. Case 2 was asymptomatic, with two copies of SMN2. Asymptomatic case 3 had four copies of SMN2 exon 7, including the SMN1/2 hybrid gene. Cases 1 and 2 were treated within 1 month and case 3 at 8 months. All the patients showed improved motor function scores and did not require respiratory support. The identification of infants with SMA via NBS and early treatment improved their motor and respiratory outcomes. Thus, implementation of SMA-NBS at a nationwide scale should be considered.

Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous inherited disorder that is treatable. Although the disease usually develops at birth or during infancy, some patients develop the disease in the second to third decades of life. Collagen-like tail subunit of asymmetric acetylcholinesterase (COLQ)-related CMS is CMS with mutations in the COLQ, which results in end-plate acetylcholinesterase deficiency. Diagnostic delay is common in patients with later-onset CMS due to slow progression and fluctuating symptoms. Understanding CMS with atypical and unusual presentations is important to treat this condition effectively. Here, we report a case of COLQ-related CMS. A 10-year-old girl presented with only marked fatigue, which was provoked by exercise but improved after 30–60 min of rest. While motor nerve conduction velocity was normal, a compound muscle action potential (CMAP) with four peaks was recorded. Repetitive stimulation of the accessory nerve exhibited a decrease in CMAP amplitude. Genetic tests revealed compound heterozygous mutations in COLQ (c.1196-1_1197delinsTG and c.1354C>T). Treatment with salbutamol improved fatigue but not the electrophysiological markers. Thus, significant fatigue is a hallmark of COLQ-related CMS; early diagnosis is essential for ensuring appropriate treatment.