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Review
. 2022 Jul 23;17(1):287.
doi: 10.1186/s13023-022-02422-6.

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

Julia B Hennermann  1 , Eva M Raebel  2 , Francesca Donà  3 , Marie-Line Jacquemont  4 , Graziella Cefalo  5 , Andrea Ballabeni  3 , Dag Malm  6
Affiliations
Review

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

Julia B Hennermann et al. Orphanet J Rare Dis. .

Abstract

Background: Alpha-mannosidosis is a rare autosomal recessive lysosomal storage disorder (LSD) caused by reduced activity of alpha-mannosidase. Clinical manifestations include skeletal dysmorphism, mental impairment, hearing loss and recurrent infections. The severe type of the disease leads to early childhood death, while patients with milder forms can live into adulthood. There are no mortality studies to date. 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.

Methods: Clinicians and LSD patient organisations (POs) from 33 countries were invited to complete a questionnaire between April-May 2021. Cause of death and age at death was available for 15 patients. A literature review identified seven deceased patients that met the inclusion criteria.

Results: Median age at death for patients reported by clinicians/POs was 45 years (mean 40.3 ± 13.2, range 18-56, n = 15); 53% were female. One death occurred during the patient's second decade of life, and 14 out of 15 deaths (93.3%) during or after the patients' third decade, including four (26.7%) during their sixth decade. Median age at death for patients identified from the literature was 4.3 years (mean 15.7 ± 17.0, range 2.2-41, n = 7); two were female. Four of the seven patients (57.1%) died within the first decade of life. Seven of 15 deaths (46.7%) reported by clinicians/POs were recorded as pneumonia and three (20.0%) as cancer. Other causes of death included acute renal failure due to sepsis after intestinal perforation, decrease of red blood cells of unknown origin, kidney failure with systemic lupus erythematosus, aortic valve insufficiency leading to heart failure, and dehydration due to catatonia. Three out of seven causes of death (42.9%) reported in the literature were associated with septicaemia, two (28.6%) with respiratory failure and one to pneumonia following aspiration.

Conclusions: This study suggests that pneumonia has been the primary cause of death during recent decades in untreated patients with alpha-mannosidosis, followed by cancer. Determining the causes of mortality and life expectancy in these patients is crucial to further improve our understanding of the natural history of alpha-mannosidosis.

Keywords: Alpha-mannosidosis; Cause of death; MAN2B1; Mortality; Natural history.

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Conflict of interest statement

JBH has received consulting fees and/or travelling expenses by Amicus, Chiesi Farmaceutici S.p.A and Takeda; EMR is employed by the Rare Disease Research Partners, which supplies various professional services to Chiesi Farmaceutici S.p.A.; FD and AB are employees of Chiesi Farmaceutici S.p.A; GC has received advisory board fees from Chiesi Farmaceutici S.p.A.; M-LJ and DM have no competing interests to declare.

Figures

Fig. 1
Fig. 1
Flow diagram of responses from clinicians and patient organisations. N refers to the number of clinicians or patient organisations
Fig. 2
Fig. 2
Year of death and age at death (years) of patients from clinicians/POs (blue) and the literature (orange) by (a) data source and sex and (b) data source and cause of death
See this image and copyright information in PMC

References

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