ABCA3 deficiency dramatically improved by azithromycin administration

Nishida, Daisuke; Kawabe, Shinji; Iwata, Nakao; Cho, Kazutoshi

doi:10.1111/ped.14487

Cited by 7 publications

(3 citation statements)

References 5 publications

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“…Although the exact mechanism of this therapy remains unclear, improvements in respiratory function have been reported with azithromycin treatment. [ 12 ] In several cases, improvements in patients with interstitial lung disease have been reported by applying hydroxychloroquine. [ 13 , 14 ] However, it should be noted that no such therapeutic regimen was prescribed in this case.…”

Section: Discussionmentioning

confidence: 99%

ABCA3 mutation-induced congenital pulmonary surfactant deficiency: A case report

Lei,

Wan,

Liu

2024

Medicine

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Introduction: Congenital surfactant deficiency, often caused by mutations in genes involved in surfactant biosynthesis such as ABCA3, presents a significant challenge in neonatal care due to its severe respiratory manifestations. This study aims to analyze the clinical data of a newborn male diagnosed with pulmonary surfactant metabolism dysfunction type 3 resulting from ABCA3 gene mutations to provide insights into the management of this condition. Patient concerns: A newly born male child aged 1 day and 3 hours was referred to our department due to poor crying and shortness of breath. Diagnosis: Primary diagnoses by the duty physicians were: neonatal pneumonia, neonatal respiratory failure, persistent neonatal pulmonary hypertension, birth asphyxia, myocardial damage, and arteriovenous catheterization. Genetic test revealed a compound heterozygous variant in the ABCA3 gene. One allele may be exon variant c.4561C>T, the second allele may be intron variant c.1896 + 2_1896 + 17del. The associated disease included pulmonary surfactant metabolism dysfunction type 3. Interventions: He was initially treated with an antiinfective therapeutic regimen. Outcomes: The family was informed of this condition and signed off, and the child died. Conclusion: Hereditary pulmonary surfactant deficiency is a rare and untreatable disease. The case highlights the challenges in managing congenital surfactant deficiencies and emphasizes the need for heightened awareness of this rare cause of infant respiratory failure.

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Section: Discussionmentioning

confidence: 99%

ABCA3 mutation-induced congenital pulmonary surfactant deficiency: A case report

Lei,

Wan,

Liu

2024

Medicine

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“…Most neonates presenting acute respiratory distress would initially receive surfactant replacement therapy, which may lead to a clinical response initially but not maintained in the longer term. Other drug treatments include corticosteroids, hydroxychloroquine, and azithromycin have been reported to be effective in some cases with ABCA3 mutations ( Hayes et al, 2012 ; Thouvenin et al, 2013 ; Nishida et al, 2021 ; Shaaban et al, 2021 ). Immunosuppression with corticosteroids are the preferred choice, administered intravenous methylprednisolone or oral prednisolone.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Report of Two Cases of Interstitial Lung Disease Caused by Novel Compound Heterozygous Variants in the ABCA3 Gene

et al. 2022

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Interstitial lung disease (ILD) is a heterogeneous group of pulmonary disorders involving the lung interstitium and distal airways, also known as diffuse lung disease. The genetic defects resulting in alveolar surfactant protein dysfunction are a rare cause of ILD in pediatric patients. We report two unrelated pediatric patients with shortness of breath, dyspnea and hypoxemia, and the chest CT findings including patchy ground-glass opacity in both lung fields, suggestive of diffuse ILD. One patient was a full-term male infant who had shortness of breath a few hours after the birth, and then developed into severe respiratory distress syndrome (RDS). Whole exome sequencing revealed novel compound heterozygous variants in the ABCA3 gene (NM_001,089.3): paternally inherited c.4035+5G > A and c.668T > C (p.M223T), and maternally inherited c.1285+4A > C. The second patient was a 34-month-old boy with onset of chronic repeated cough and hypoxemia at 9 months of age. We unveiled novel compound heterozygous ABCA3 variants (c.704T > C, p.F235S; c.4037_4040del, p.T1346Nfs*15) in this patient. Surfactant protein dysfunction due to bi-allelic mutations in the ABCA3 gene was the cause of ILD in two patients. The novel mutations found in this study expanded the spectrum of known mutations in the ABCA3 gene.

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“…Reviewing the published literature, about two-thirds of the patients reported to date presented during the neonatal period, had a severe clinical course with global respiratory insufficiency and died in the first year of life 2 3. The literature search for children surviving beyond their first birthday retrieved very limited data from a total of 43 subjects from various case reports or miniseries 5–29. Patients surviving longer often carried a compound heterozygous genotype and had less oxygen supplementation during the neonatal period.…”

Section: Introductionmentioning

confidence: 99%

ABCA3-related interstitial lung disease beyond infancy

Seidl

Knoflach

et al. 2023

Thorax

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BackgroundThe majority of patients with childhood interstitial lung disease (chILD) caused by pathogenic variants in ATP binding cassette subfamily A member 3 (ABCA3) develop severe respiratory insufficiency within their first year of life and succumb to disease if not lung transplanted. This register-based cohort study reviews patients with ABCA3 lung disease who survived beyond the age of 1 year.MethodOver a 21-year period, patients diagnosed as chILD due to ABCA3 deficiency were identified from the Kids Lung Register database. 44 patients survived beyond the first year of life and their long-term clinical course, oxygen supplementation and pulmonary function were reviewed. Chest CT and histopathology were scored blindly.ResultsAt the end of the observation period, median age was 6.3 years (IQR: 2.8–11.7) and 36/44 (82%) were still alive without transplantation. Patients who had never received supplemental oxygen therapy survived longer than those persistently required oxygen supplementation (9.7 (95% CI 6.7 to 27.7) vs 3.0 years (95% CI 1.5 to 5.0), p=0.0126). Interstitial lung disease was clearly progressive over time based on lung function (forced vital capacity % predicted absolute loss −1.1% /year) and on chest CT (increasing cystic lesions in those with repetitive imaging). Lung histology pattern were variable (chronic pneumonitis of infancy, non-specific interstitial pneumonia, and desquamative interstitial pneumonia). In 37/44 subjects, theABCA3sequence variants were missense variants, small insertions or deletions with in-silico tools predicting some residual ABCA3 transporter function.ConclusionThe natural history of ABCA3-related interstitial lung disease progresses during childhood and adolescence. Disease-modifying treatments are desirable to delay such disease course.

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ABCA3 deficiency dramatically improved by azithromycin administration

Abstract: Fig. S1. The patient's left foot near the malleolus medialis when he entered the hospital.

Cited by 7 publications

References 5 publications

ABCA3 mutation-induced congenital pulmonary surfactant deficiency: A case report

ABCA3 mutation-induced congenital pulmonary surfactant deficiency: A case report

Case Report: Report of Two Cases of Interstitial Lung Disease Caused by Novel Compound Heterozygous Variants in the ABCA3 Gene

ABCA3-related interstitial lung disease beyond infancy

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