Peer-reviewed article
Neurodevelopmental Profile of Children With MARS1 -Related Pulmonary Alveolar Proteinosis: A Cohort Study.
Catherine Grosmaitre, Mathis Le Bellego, Nathalie Boddaert, Pauline Chaste, Alice Hadchouel ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This study examined the intellectual and adaptive functioning of 16 children with MARS1-related pulmonary alveolar proteinosis (PAP), a rare genetic lung disease treated with methionine supplementation. Children showed borderline to mild intellectual disability with mean IQ of 72, and significant deficits in communication, daily living skills, socialization, and motor abilities. The neurodevelopmental impairments were consistent across the group despite methionine treatment, suggesting the disease affects cognitive development. The findings highlight the need for routine developmental monitoring and multidisciplinary care in these children.
Key points
- Mean Full-Scale IQ was 72.25 (SD = 16.85), indicating borderline to mild intellectual disability
- Adaptive behavior composite scores averaged 69.75 (SD = 23.58) with deficits across communication, daily living skills, socialization, and motor domains
- Neurodevelopmental impairments were relatively homogeneous across the 16-child cohort
- Impairments persisted despite methionine supplementation started at median age of 6 months
- Study population aged 14 months to 7.3 years, followed at Necker-Enfants Malades Hospital in Paris
Limitations
This is a descriptive cohort study of a rare disease in one hospital setting with a small sample size (16 children, only 8 assessed with IQ testing), so findings may not generalize to all children with MARS1-related PAP or other populations. The study does not include a comparison group, making it unclear whether the neurodevelopmental profile is specific to this disease or affected by other factors.
Abstract
ImportancePulmonary alveolar proteinosis (PAP) is a rare pulmonary disorder characterized by alveolar surfactant accumulation leading to respiratory impairment. MARS1 mutations lead to an early onset PAP associated in a setting of multi-organ involvement and respond to high-dose methionine supplementation. While pulmonary manifestations of MARS1-related PAP and their response to methionine are well documented, its potential impact on cognitive and adaptive functioning in pediatric patients remains poorly understood. Understanding the neurodevelopmental profile of children with MARS1-related PAP is essential for optimizing comprehensive care and long-term outcomes. ObjectiveTo characterize the neurodevelopmental profile of children with MARS1-related PAP by assessing intellectual functioning and adaptive behavior using standardized neuropsychological measures and parent-reported questionnaires. DesignObservational cohort study including 16 pediatric patients with MARS1-related PAP aged 14 months to 7.3 years, followed at the Necker-Enfants Malades Hospital (Paris, France) and treated with methionine. Intellectual functioning was assessed using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) when age-appropriate, and adaptive behavior was evaluated via the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) through parent interviews. ResultsSixteen children with MARS1-related PAP underwent the full evaluation. Methionine was started at a median age of 6 months (IQR [5, 15]). Eight of them were able to undergo the WPPSI-IV assessment. The mean Full-Scale IQ was 72.25 (SD = 16.85), indicating borderline to mild intellectual disability relative to normative data. Adaptive behavior composite scores on the VABS-II averaged 69.75 (SD = 23.58), reflecting significant deficits across communication, daily living skills, socialization, and motor domains. The neurodevelopmental impairments were relatively homogeneous across the cohort. ConclusionsChildren with MARS1-related pulmonary alveolar proteinosis exhibit marked impairments in intellectual and adaptive functioning, suggesting a consistent neurodevelopmental profile associated with the disease, and despite methionine supplementation. These findings highlight the need for routine cognitive and developmental monitoring in pediatric PAP patients and support the development of multidisciplinary interventions addressing both respiratory and neurodevelopmental outcomes.
Findings the Hub has extracted
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- Intervention
- High-dose methionine supplementation started at median age of 6 months
- Population
- 16 children aged 14 months to 7.3 years with MARS1-related PAP
Key finding
Mean Full-Scale IQ of 72.25 (SD = 16.85) indicating borderline to mild intellectual disability despite methionine treatment