Study of the Prevalence of Acid Sphingomyelinase Deficiency/Niemann Pick AB and B Disease in Patients With Diffuse Interstitial Lung Disease

With the prevalence of ASMD estimated to be between 0.4 and 0.6/100,000 births, is probably under-diagnosed because it is not well known. Based on the current literature, no prevalence studies have been carried out, particularly in patients with interstitial lung disease (ILD). Similarly, no decision-making algorithm has been established for screening for ASMD in this participant population. Therefore, we aim to conduct this multicenter clinical trial to assess the relevance of implementing a decision algorithm to optimise screening for ASMD. Validation of this algorithm could provide clinicians with an additional diagnostic tool to improve the management of this disease and prevent its progression. Olipudase-alfa, a specific treatment for ASMD available from 2022, could thus benefit a greater number of people with disease who have been under-diagnosed.

The literature reports an association between chronic visceral ASMD (type B) and the presence of ILD, usually accompanied by splenomegaly or splenectomy (whatever the medical reason or cause), low HDL cholesterol, thrombocytopenia, with a higher frequency in cases of parental consanguinity.

ILD is common in the general population, therefore, in order to limit the number of differential diagnoses, the population to be studied will consist of participants aged between 15 years and 3 months and 60 years, with diffuse interstitial lung disease with ground-glass opacities on chest CT scan certified by a pulmonologist/radiologist or internist. We will propose acid sphingomyelinase activity testing in this population in case of splenomegaly (palpable spleen or craniocaudal length ≥ 13 cm) or splenectomy and/or thrombocytopenia (platelets < 150 G/L) and/or low HDL cholesterol (<0.4 g/l or 1. 03 mmol/l) and/or parental consanguinity increase the sensitivity of ASMD screening.

Considering that detection of ASMD after the age of 60 would not lead to a modification in current management, it was decided to limit the population to 60 years of age. Screening for ASMD, a very rare disease, can only be reasonably performed in a limited and selected population.

Description of actions and procedures added by the research :

• Venous blood collection (4ml EDTA tube) for the determination of :

• acid sphingomyelinase enzyme activity in all participants included in the study. The determination of acid sphigomyelinase enzyme activity will be performed using a multiplex blotting assay that allows simultaneous determination of acid sphigomyelinase activity (ASMD) by tandem MS/MS mass spectrometry, but also Beta-glucocerebrosidase (Gaucher disease), alpha-galactosidase (Fabry disease), Maltase Acid (Pompe disease), Galactocerebrosidase (Krabbe disease), Alpha-L iduronidase (control enzyme) (MPSI)).
• if acid sphingomyelinase activity < 1.82 μmol/h/l (decreased) is detected, the concentration of lysoSM should be determined on the same sample.
• Appropriate participant management in the event of a positive ASMD screening.

Inclusion criteria

• Interstitial lung disease with ground-glass lesions on a chest CT scan certified by a pneumologist/radiologist or internist.
• At least one of the following criteria :

• Splenomegaly (palpable spleen or craniocaudal length ≥ 13 cm)
• Splenectomy
• Thrombocytopenia (platelets < 150 G/L)
• Low HDL-cholesterol (<0.4 g/l or 1.03 mmol/l)
• Notion of parental consanguinity
• Have given their written informed consent, in accordance with regulations.
• Affiliated to the social security system or entitled beneficiary (excluding AME).

Exclusion criteria

• Inability to understand the information provided.
• Under guardianship, curatorship or legal protection.
• Under restraint or deprived of liberty by judicial or administrative decision.