Success of methionine supplementation for treatment of alveolar proteinosis with confirmed MARS-1 mutation: a case report

Introduction: Alveolar proteinosis is a very rare disease characterized by the accumulation of surfactant phospholipids and lipoproteins in the alveoli. The disease can be caused by mutations in various genes. This includes a mutation in the MARS-1 gene. In addition to pulmonary symptoms, liver disease, developmental delay, muscular hypotonia, dystrophy and anemia have been described in association with the mutation. Some studies have shown a positive effect of methionine supplementation on the course of the disease. When we diagnosed a patient with alveolar proteinosis in the context of a MARS-1 mutation at our center in the summer of 2024, we decided, with the parent’s consent, to initiate and evaluate methionine supplementation.

Patient: Our patient had frequent recurrent sever lower respiratory tract infections since the age of a few months, which required several hospitalizations. Additionally, he suffered from severe diffuse lung disease and increasing respiratory insufficiency, only responsive to high doses of prednisolone. In addition to pulmonary deterioration, our patient showed psychomotor developmental delay, hepatomegaly, fever attacks and increased inflammation parameters in the first year of life.

Radiological and bronchoscopic findings revealed characteristics of pulmonary alveolar proteinosis (PAP). A therapy with prednisolone and mycophenolate mofetil (MFF) was initiated to treat the autoinflammation, and a whole-lung lavage was considered.

Genetic testing revealed two class 3 mutations in the MARS-1 gene, which led to the diagnosis of alveolar proteinosis in the context of a MARS1 mutation at the age of 21 months.

In addition to a tapering prednisolone and MMF, we started methionine supplementation, which was level-controlled managed (target level 45–500 μM).

Results: Just a few weeks after starting methionine supplementation and after cessation of prednisolone, and mycophenolate mofetil, the patient no longer required oxygen therapy. Even a confirmed COVID-19 infection did not result in significant impairment, in contrast to previous viral infections. Consistent with the clinical improvements, a follow-up CT scan after two months revealed a significant reduction in the previously observed diffuse opacity. Similarly, a follow-up bronchoalveolar lavage showed much less milky appearance. Additionally, there was noticeable improvement in gross motor skills, oral motor function, and food intake.

Conclusion: The introduction of methionine supplementation in the second year of life in a child with alveolar proteinosis and a confirmed MARS-1 mutation resulted in significant clinical and radiological improvement within two months.

Publication History

Article published online:
28 February 2025