SNPMiner Trials by Shray Alag


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Report for Mutation S567L

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There is one clinical trial.

Clinical Trials


1 Oral or Enteral Administration of Methionine in Patients With Pulmonary Alveolar Proteinosis by Mutation of the MARS Gene.

The purpose of this study is to determine the safety and tolerance of an oral administration of methionine in the treatment of pulmonary alveolar proteinosis due to the double mutation Ala393Thr / Ser567Leu in the MARS gene. This disease is very severe and especially leads to chronic respiratory insufficiency. There is no curative treatment for this disease. The MARS gene encodes the methionine tRNA synthetase (MetRS). Mutations in this gene leads to a defect in MetRS function. In cultured mutated yeast, addition of methionine in culture medium restores MetRS function. Therefore, we hypothesized that treatment of patients with methionine could have beneficial effects on the disease.

NCT03887169 Pulmonary Alveolar Proteinosis Mutation Ala393Thr of the MARS Gene mutationSer567Leu of the MARS Gene Drug: Methionine Drug: Vitamin B12, B9, B6, C supplementation Diagnostic Test: Methionine/homocysteine Dosage Diagnostic Test: Thoracic CT scan Diagnostic Test: Abdominal and liver ultrasound. Diagnostic Test: Brain MRI
MeSH: Pulmonary Alveolar Proteinosis
HPO: Alveolar proteinosis

The purpose of this study is to determine the safety and tolerance of an oral administration of methionine in the treatment of pulmonary alveolar proteinosis due to the double mutation Ala393Thr / Ser567Leu in the MARS gene. --- Ala393Thr --- --- Ser567Leu ---

Inclusion Criteria: - Minor Patient under the age of 10 with alveolar proteinosis by double mutation Ala393Thr and SER567LEU of the MARS gene, genetically proven. --- Ala393Thr --- --- SER567LEU ---

- Patient for which methionine can be administered orally or by enteral probe (Nasogastric or gastrostomy probe) - Signed Informed consent form by parents / legal guardian Exclusion Criteria: - Patient with alveolar proteinosis by other mutations of the MARS gene - Patient with alveolar proteinosis secondary to another etiology or without identified cause - Refusal to participate in the study - High blood pressure requiring drug treatment - Heart failure - Known hypersensitivity to one of the substances used or potentially used in the study: methionine, vitamins B6, B12, B9 and C - Pre-Hypermethioninemia (Methioninemia > + 2 DS of normal for age) whatever the cause Inclusion Criteria: - Minor Patient under the age of 10 with alveolar proteinosis by double mutation Ala393Thr and SER567LEU of the MARS gene, genetically proven. --- Ala393Thr --- --- SER567LEU ---

Primary Outcomes

Description: No adverse event from day 0 to day 75.

Measure: Tolerance Assessment

Time: From day 0 to day 75

Secondary Outcomes

Description: number of cycles per minute

Measure: Respiratory rate (cycles /min)

Time: At day 0, day 15, day 30, day 45, day 60, day 75

Description: Flow in L/min

Measure: Oxygen need (L/min)

Time: At day 0, day 15, day 30, day 45, day 60, day 75

Description: Presence or absence of signs

Measure: Respiratory signs of struggle

Time: At day 0, day 15, day 30, day 45, day 60, day 75

Description: Lesions appearance on thoracic CT scan, scored form 0 to 4

Measure: Lung lesions

Time: At Day 60

Description: Fluid examination

Measure: Lipo-proteinaceous material

Time: At each bronchial-alveolar washes during the 2,5 months

Description: To evaluate Nutritional status

Measure: Weight

Time: At Day 15, Day 30, Day 45, Day 60, Day 75

Description: To evaluate Nutritional status

Measure: mid upper arm circumference / head circumference rapport

Time: At Day 15, Day 30, Day 45, Day 60, Day 75

Description: liver damage evaluate by physician during clinical examination

Measure: Hepatomegaly

Time: At Day 0, Day 15, Day 30, Day 45, Day 60, Day 75

Description: liver damage evaluate by biological parameters : ASAT, ALAT, GGT, PAL, Bilirubin

Measure: cholestasis and hepatic cytolysis

Time: At Day 0, Day 15, Day 30, Day 60, Day 75

Description: liver damage evaluate by echography

Measure: Hepatomegaly

Time: At Day 0 and Day 60

Description: Biological parameters to evaluate Systemic inflammation

Measure: C reactive protein

Time: At Day 0, Day 30, Day 60

Description: Biological parameters to evaluate Systemic inflammation

Measure: sedimentation rate

Time: At Day 0, Day 30, Day 60

Description: Biological parameters to evaluate Systemic inflammation

Measure: Immunoglobulin G level

Time: At Day 0, Day 30, Day 60

Description: Biological parameters to evaluate inflammatory anaemia

Measure: Haemoglobin level

Time: At Day 0, Day 30, Day 60


HPO Nodes


Alveolar proteinosis
Genes 9
ABCA3 SFTPB CSF2RB SFTPC SLC7A7 MARS1 SFTPB SLC7A7 CSF2RA