Oral Pyridostigmine‐responsive Visceral Myopathy With ACTG2 Mutations

To the Editor: Chronic intestinal pseudo-obstruction (CIPO) is a rare intestinal motility disorder that can be fatal if not treated properly. CIPO diagnosis is basically clinical in the absence of mechanical obstruction, and therapy with intravenous neostigmine (anticholinergic inhibitor) is recommended in acute episodes. Recently, variants in the ACTG2 gene, encoding enteric smooth muscle actin, have been identified (1). Although the effectiveness of pyridostigmine (a longer-acting cholinesterase inhibitor) in adult CIPO has been reported (2,3), this is the first report of its effectiveness in 2 children with CIPO harboring ACTG2 variants (Fig. 1). The first ACTG2 deletion mutation (del exons 8–9) was identified in case 1, an 11-year-old girl with CIPO affecting the small intestine. To date, all disease-associated ACTG2 mutations reported have been missense mutations (4,5). A novel missense variant (p. Pro39Arg) was identified in case 2, a 5-year-old girl with CIPO affecting the colon with congenital megacystis but no microcolon. Neostigmine (0.5 mg in 50 mL normal saline) was administrated by intravenous infusion at 0.5 mg/h for an hour. The infusion was increased from 0.5 to 2.5 mg/day over 1 to 5 hours in case 1 (≥30 kg), and from 0.025 to 0.04 mg · kg−1 · day−1 in case 2 (<30 kg). After 10 days of full dosage, the therapy was changed to oral pyridostigmine, at a dosage of 180 mg/day (case 1) and 7 mg · kg−1 · day−1 (case 2) without side effects. In response to treatment with oral pyridostigmine, the length of hospital stay and dependency on parenteral nutrition were reduced in the patients.FIGURE 1: Histological analysis of small intestinal tissues from the case 1 proband (A–C) and of colon tissues from the case 2 proband (D–F). Detectable changes were observed in the structural organization and expression of smooth muscle actin in the proximal (A, D) and most-affected distal (B, E) intestines (×100). A, Muscularis propria, proximal small intestine. B, Decreased expression in the muscularis propria, distal intestine. D, Muscularis propria, proximal colon. E, Decreased expression and reduced muscle thickness of the muscularis propria, distal colon. C and F, Ganglion cells are indicated with circles (hematoxylin and eosin staining, ×200).