Disease manifestations and burden of illness in patients with acid sphingomyelinase deficiency (ASMD)

Orphanet J Rare Dis 2017 Feb 23;12(1):41. doi: 10.1186/s13023-017-0572-x.

PMID: 28228103

Margaret M McGovern, Ruzan Avetisyan, Bernd-Jan Sanson, Olivier Lidove

Highlights: While knowledge about ASMD is evolving, more evidence about ASMD and the natural history across the disease spectrum is needed, to improve disease recognition, timely diagnosis and appropriate disease management.

Abstract:

Background: Acid sphingomyelinase deficiency (ASMD), a rare lysosomal storage disease caused by SMPD1 mutations, is an autosomal recessive genetic condition. ASMD had previously been categorized as Niemann-Pick disease (NPD) types A (NPD A) and B (NPD B) (NPD B). NPD A is linked with a consistently debilitating disease course, characterized by rapidly progressing psychomotor deterioration and mortality by the age of three years, most commonly due to respiratory failure. Patients with NPD B, on the other hand, may have a wide range of clinical phenotypes and life expectancies. Almost all of the patients have hepatosplenomegaly and an atherogenic lipid profile, and the majority of them have interstitial lung disease with increasing pulmonary function decline and hematologic abnormalities, including cytopenias. Liver problems, cardiac disease, skeletal abnormalities, and growth delays are all frequent clinical symptoms. Some ASMD patients who live into infancy have intermediate phenotypes (variant NPD B), which include a combination of non-neurologic and mild to severe neurologic symptoms. Patients with NPD B face a significant physical and psychosocial burden as a result of their condition. Shortness of breath, joint or limb pain, stomach pain, bleeding, and bruises are all common symptoms. Chronic fatigue, restricted physical or social engagement, and difficulty completing everyday activities or working are all common symptoms of the disease. Many individuals die before or during their adolescence, usually as a result of pneumonia, respiratory failure, or liver failure.

Conclusion: Symptom management and supportive care are the only therapies available. An enzyme replacement therapy, which is presently in clinical trials, is believed to be the first treatment to target the disease's underlying pathophysiology. Early detection and treatment are critical for lowering the risk of consequences. While our understanding of ASMD is growing, additional data regarding the disease and its natural history across the disease spectrum is needed to enhance disease identification, diagnosis, and treatment.

Keywords: ASMD, Acid sphingomyelinase deficiency, Burden of illness, Disease manifestations, Lysosomal storage disorder, Natural history, Niemann-Pick disease types A and B