Causes of death in 184 patients with type 1 Gaucher disease from the United States who were never treated with enzyme replacement therapy.
Treatment for type 1 Gaucher disease (GD1) decreases morbidity from hematological cytopenias, hepatosplenomegaly and bone complications. Consequently, untreated symptomatic patients for study of late outcomes are hard to find. We identified 184 untreated GD1 patients (67.4% Ashkenazi; splenectomy 51.1%) who died between 1950 and 2010. Here, we report confirmed causes of death for these patients compared with the overall US population. Median age of death 66years (2-97years); causes of death (COD) with a high proportional mortality rate (PMR) included malignancies (PMR 1.57), suicide/drug overdose (PMR 3.86), liver disease (PMR 4.76) and septicemia (PMR 9.22). PMRs for CNS/gastrointestinal bleeding, pulmonary hypertension, post-splenectomy complications and Parkinsonism were also increased. PMR for heart disease (0.33) was significantly decreased. Average age at death was normal for heart disease, septicemia, suicide, and malignancies but younger for liver disease and Parkinsonism. COD more prevalent in splenectomy patients included liver disease, septicemia, pulmonary hypertension and GI bleeding. With timely diagnosis, improved risk assessment and obsolescence of splenectomy, GD1-associated malignancies, liver disease, septicemia, pulmonary hypertension, suicide and drug dependency may decrease with early institution of appropriate treatment. Our population of untreated patients is a valuable historical control for studies of the effect of GD1 treatment on premature mortality.
The Dr John T Macdonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, 1601 12th Avenue, Miami, FL 33136, USA; University Research Foundation for Lysosomal Storage Diseases, 7367 Wexford Terrace, Boca Raton, FL 33433, USA. Electronic address: N.weinreb@med.miami.edu.
Neal J
NJ
Weinreb
The Dr John T Macdonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, 1601 12th Avenue, Miami, FL 33136, USA. Electronic address: DBarbouth@med.miami.edu.
Deborah S
DS
Barbouth
Department of Pathology, University of Pittsburgh, PA 15261, USA. Electronic address: Leere@msx.upmc.edu.
Robert E
RE
Lee
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D056947:Enzyme Replacement Therapy; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013156:Splenectomy; D014481:United States / Q000453:epidemiology; D055815:Young Adult
Causes of death; Gaucher disease; Proportional mortality; Splenectomy; Untreated patients