齋藤 和由

UNLABELLED: Propionic acidemia (PA) is a known cause of secondary dilated cardiomyopathy (DCM). However, little is known about how diet and heart failure treatment impact long-term cardiac outcomes in adult PA patients. We report the successful treatment of metabolic disease and secondary DCM-associated heart failure in a 20-year-old male patient with neonatal-onset PA and intellectual disability. At age 19 years, echocardiography had revealed DCM without impaired cardiac contractility. At age 20 years, he developed heart failure, presumably from a common cold infection, and was hospitalized. Acute heart failure treatment improved his symptoms, leading to discharge, but they worsened again, necessitating re-admission. He then was discharged only after successfully adding carvedilol and pimobendan to his medication. Six weeks later, however, he developed hyperammonemia with elevated serum propionyl carnitine and decreased free carnitine levels. He received acute phase treatment for this metabolic crisis and his diet therapy was readjusted, including by reducing natural protein. In the following 5 years, while continuing and slightly adapting heart failure medication and dietary regimens, the patient's cardiac function stably improved and his diuretic dose could be reduced. Our findings support that careful diet therapy and modulation of heart failure medication can improve cardiac function in PA patients with DCM. LEARNING OBJECTIVE: Neonatal-onset propionic acidemia (PA) tends to be the most severe form of PA and life-threatening metabolic disease. Even if the impact of the disease can be ameliorated by adapting the diet, later in life these patients often develop symptoms such as intellectual disability, metabolic crises, and dilated cardiomyopathy (DCM), as observed in this case. This case demonstrates that heart failure medication and dietary therapy can help protect against metabolic disease and DCM-associated heart failure in an adult patient with neonatal-onset PA.

BACKGROUND: Kawasaki disease (KD) onset has been suggested to be associated with infections and various environmental factors. However, research on whether the delivery type plays a role in KD development is limited. This study investigated whether cesarean section (CS) or vaginal delivery (VD) is associated with KD onset using a large administrative claims database in Japan. METHOD: We conducted a case-control study using the JMDC Claims Database from January 2005 to December 2021. Data on children born via CS or VD and their mothers were collected. KD patients were identified from the source population, and controls without KD were randomly selected based on sex, age and registration time, each matched to 4 controls using a risk-set sampling technique. We analyzed the association between delivery type and KD onset using multivariate conditional logistic regression, defining KD as the primary outcome based on specific criteria. RESULTS: Case-control matching created 3363 pairs of cases (n = 3363) and controls (n = 13,363). The proportions of CS, maternal age, Charlson Comorbidity Index, presence of older siblings and low birth weight infants were significantly different between the cases and controls. In the multivariate analysis, KD onset was associated with CS [odds ratio (OR): 1.12; 95% confidence interval (CI): 1.02-1.24], the presence of older siblings (OR: 1.11; 95% CI: 1.02-1.21), lower birth weight (1001-2500 g) (OR: 1.22; 95% CI: 1.04-1.43) and antibiotic use (OR: 1.12; 95% CI: 1.02-1.24). CONCLUSIONS: The risk of developing KD may be influenced by the delivery type (CS or VD), the presence of older siblings, low birth weight and antibiotic use.

UNLABELLED: Most cases of pulmonary arteriovenous malformation (PAVM) are associated with hereditary hemorrhagic telangiectasia (HHT). HHT is typically caused by loss-of-function gene mutations in the genes ENG, ACVRL1, or SMAD4, all participating in transforming growth factor β (TGF-β) family signaling pathways. We describe the case of an 11-year-old Japanese girl with PAVM, with no known family history of HHT or similar disease. She was found to carry a novel nonsense variant in SMAD9 (SMAD9-p. T267*), which we speculate contributed to her disease, because SMAD9 also participates in TGF-β family signaling pathways. SMAD9 mutations have been linked with pulmonary arterial hypertension (PAH), and, hence, mutations in SMAD9-as for ENG, ACVRL1, and SMAD4-may predispose to both PAH and HHT(-characteristic) disease features. The PAVM in our patient spread diffusely inside the lower lobe of the left lung, and coil embolization was considered difficult. Therefore, after feasibility assessment by performing a balloon occlusion test during cardiac catheterization, left lower lobectomy was performed. The patient's dyspnea recovered well postoperatively, and two years later an increase in left lung volume was observed and disease symptoms had not recurred. Thus, if PAVM spreads diffusely in a certain lung area, surgical treatment can be a viable option. LEARNING OBJECTIVE: SMAD9 gene mutations have been linked to pulmonary arterial hypertension (PAH). However, their associations with hereditary hemorrhagic telangiectasia (HHT) or pulmonary arteriovenous malformation (PAVM), which usually is HHT-associated, have not been reported previously. Our PAVM patient carrying a SMAD9 variant suggests that mutations in this gene, like in others participating in TGF-β family signaling pathways (like ENG, ACVRL1, and SMAD4), predispose to both PAH and HHT(-characteristic) disease features. Diffuse PAVM confined to a lung area may be treated by lobectomy.