The impact of interstitial lung disease in patients with acid sphingomyelinase deficiency (ASMD) - A case series

Background

Lysosomal storage diseases (LSD) are inherited diseases caused by mutations affecting genes encoding the function of lysosomal enzymes. Acid sphingomyelinase deficiency (ASMD) is an ultra-rare, progressive, and often fatal LSD with an estimated prevalence of 1-in-50,000–250,000 individuals. The PrevASMD study established the ASMD prevalence in Spain at 35 patients. Almost all present asymptomatic interstitial lung disease (ILD), since >90 % patients with chronic visceral ASMD have radiographic evidence of ILD.

Objective

This case series aims to emphasize the importance of ASMD in adult and pediatric patients with ILD, and to underline the consideration of pulmonary involvement as a key feature of the multisystemic manifestation of ASMD.

Methods

This case series describes seven adult and pediatric cases of ASMD in Spain. All presented with pulmonary function impairment. Data were collected on clinical presentation, diagnostic workup, pulmonary function tests, imaging studies, and patient outcomes during follow up.

Results

Sphingomyelin accumulation in ASMD leads to multi-systemic disease involving spleen, liver, lungs, bone marrow, and lymph nodes. Almost all patients presented with asymptomatic ILD, but not all of them exhibited respiratory symptoms and not all were referred to pulmonologists. Periodic assessments included pulmonary function testing (forced vital capacity and diffusing capacity for carbon monoxide), O2 saturation, and exercise tolerance testing.

Conclusion

ASMD patients presented with different target organ involvement, with lung involvement contributing significantly to patient morbi-mortality. ASMD diagnostic suspicion among pulmonologists treating ILD is thus crucial, as multidisciplinary monitoring of ILD as a feature of ASMD can ensure its correct management and follow-up.