What metabolic and hormonal disturbances are associated with Gaucher disease?

The clinical symptoms of Gaucher disease can be accompanied by metabolic and hormonal disturbances that may affect a patient’s quality of life and general health.1 The metabolic and hormonal disturbances reported in patients with Gaucher disease Type 1 are highlighted below.

Some patients with Gaucher disease may experience low appetite; the percentage of underweight adult patients with Gaucher disease has been reported as 3%.2,3 The malnutrition rate in paediatric patients with Gaucher disease has been reported as 26%, which increased to 48% at the end of a median 64-month observation period.4 Another study found that 29% of 108 patients (mean age [standard deviation], 44.8 [16.6] years) were either overweight or obese. Moreover, patients who had been splenectomised were more likely to be overweight or obese than non-splenectomised patients (36% [9/27] vs 27% [19/81]).3

Untreated patients with Gaucher disease (n=7) were reported in one study to have an elevation in basal hepatic glucose of approximately 30% compared with controls (n=7; p<0.01).5 A study of untreated patients with Gaucher disease (n=7) and those patients treated with enzyme replacement therapy (n=35) indicated that the 11-year cumulative incidence of Type 2 diabetes mellitus was 6.6%.6 Further studies are required to explain the mechanism and origin of insulin resistance in both treated and untreated patients with Gaucher disease; the diagnostics and treatment of insulin resistance and Type 2 diabetes mellitus may be associated with long-term complications of the disease.1

Lipoprotein concentrations are altered in patients with Gaucher disease, as serum concentrations of total cholesterol, and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, are often low in untreated patients.1,7 However, low levels of HDL cholesterol are not thought to lead to atherosclerosis in patients with Gaucher disease; likewise, no increased risk for cardiovascular disease has been documented.8

One cross-sectional study evaluated levels of ghrelin (a hormone that promotes hunger),9 leptin (a hormone that regulates appetite)10 and adiponectin (a hormone that regulates glucose and lipid metabolism)11 in 15 patients with Gaucher disease Type 1 who were receiving enzyme replacement therapy for a median of 5 years (range, 3‒15 years). Eight of these patients were of a normal weight but seven were considered overweight. Metabolic syndrome was identified in eight patients, five of whom were insulin resistant. In patients with Gaucher disease, median levels of ghrelin, leptin and adiponectin were not different from healthy individuals matched for age, body mass index (BMI) and gender. However, ghrelin and adiponectin levels were positively correlated with one another, and were inversely associated with BMI, waist circumference and levels of triglycerides. Ghrelin and adiponectin levels correlated with HDL cholesterol levels, whereas leptin levels were inversely correlated with LDL cholesterol levels. BMI, waist circumference, the dosage of enzyme replacement therapy, triglyceride levels, insulin levels and insulin resistance were positively associated with leptin levels. These data indicate that patients with Gaucher disease Type 1 receiving enzyme replacement therapy could develop metabolic syndrome. It has been suggested that because leptin levels were strongly associated with insulin levels and insulin resistance, leptin could be a biomarker to assess early evidence of insulin resistance in patients with Gaucher disease.12

Many children with Gaucher disease Type 1 experience delays in growth. One study that examined 887 paediatric patients (aged <18 years), indicated that 34% had delays in growth and puberty (growth <5th percentile).13 Other studies that have assessed alterations in growth and puberty in patients with Gaucher disease Type 1 are shown in Table 1.


Table 1.
Studies assessing alterations in growth delays and puberty in patients with Gaucher disease Type 1. Reproduced with permission from Kałużna M et al. Orphanet J Rare Dis 2019; 14: 275.13


C-ANPROM/INT//7566; Date of preparation: September 2020