Mortality in patients with alpha-mannosidosis: A review of patients' data and the literature

Orphanet J Rare Dis. 2022 Jul 23;17(1):287. doi: 10.1186/s13023-022-02422-6.

PMID: 35871018

Julia B Hennermann, Eva M Raebel, Francesca Donà

Highlights: This study aimed to investigate the age at death and the causes of death of patients with alpha-mannosidosis who had not received disease-modifying treatment.

Abstract

Background: A rare autosomal recessive lysosomal storage disorder (LSD) known as alpha-mannosidosis is brought on by decreased alpha-mannosidase activity. Skeletal dysmorphism, mental disability, hearing loss, and recurrent infections are examples of clinical symptoms. Patients with the milder forms of the disease can live into adulthood, while those with the more severe forms cause early childhood death. There haven't been any research on mortality yet. In this study, patients with alpha-mannosidosis who had not received disease-modifying therapy were examined for age at death and causes of death.

Methods: Between April and May 2021, clinicians and LSD patient organizations (POs) from 33 countries were invited to respond to a questionnaire. For 15 cases, the cause of death and the age at death were known. A review of the literature revealed seven deceased patients who satisfied the requirements for inclusion.

Results: Patients reported by clinicians/POs had a median age at death of 45 years (mean 40.3 ± 13.2, range 18-56, n = 15); 53% of the patients were female. One death occurred in the patient's second decade, and 14 out of 15 deaths (93.3%) occurred in the third decade or later, including four (26.7%) in the patient's sixth decade. Patients discovered from the literature had a median age at death of 4.3 years (mean 15.7 ± 17.0, range 2.2-41, n = 7); two of the patients were female. Within the first ten years of life, four out of the seven patients (57.1%) passed away. Clinicians/POs reported 15 deaths; seven (46.7%) had pneumonia and three (20.0%) had malignancy. Acute renal failure brought on by sepsis following intestinal perforation, a drop in red blood cells of unknown origin, kidney failure brought on by systemic lupus erythematosus, an insufficient aortic valve resulting in heart failure, and dehydration brought on by catatonia were some of the other causes of death. Out of the seven reported causes of death, septicemia accounted for three (42.9%), respiratory failure for two (28.6%), and pneumonia following aspiration for one.

Conclusion: According to this study, pneumonia has been the leading cause of mortality among untreated patients with alpha-mannosidosis over the past few decades, followed by malignancy. Our knowledge of the natural history of alpha-mannosidosis must be further improved by identifying the reasons of mortality and life expectancy in these patients.

Keywords: Alpha-mannosidosis, MAN2B1, Mortality, Natural history