Zandbergen, A.A.M.

Low bone mass in Pompe disease. Muscular strength as a predictor of bone mineral density (Article)

2010-09-01T00:00:00Z

Pompe disease is an inherited metabolic myopathy caused by deficiency of acid alpha-glucosidase. The introduction of enzyme replacement therapy as treatment for the disease may change prospects for patients and may require that more attention be paid to co-morbidities such as osteoporosis. Methods: Bone mineral status was assessed in children and adults with Pompe disease and compared with reference values by means of dual energy X-ray absorptiometry (DXA) technology (GE Lunar DPX, GE Health Care). Bone mineral density (BMD) of the total body and the lumbar spine (L2-L4) was measured in adults and children; BMD of the femoral neck was measured in adults only. Exclusion criteria were: age < 4 years, severe contractures, and inability to transfer the patient. Results: 46 patients were enrolled in the study; 36 adults and 10 children. The BMD was significantly lower in Pompe patients than in healthy individuals. Sixty-seven percent of patients had a BMD Z-score below -1, 26% were classified as osteoporosis/low bone mass for chronological age (T-score < -2.5 in adults or Z-score < -2 in children), 66% had a BMD Z-score below -1 of the femoral neck, and 34% had a BMD Z-score below -1 for the lumbar spine. Osteoporosis/low bone mass for chronological age was more frequent in patients who were wheelchair-bound, but was also observed in ambulant patients. We found a significant correlation between proximal muscle strength and total body BMD. Of the 10 children, 8 (all four patients with the classic infantile form) had a low BMD. Conclusion: Low BMD is a frequent finding in patients with Pompe disease and may be causally related to decreased proximal muscle strength. BMD should be monitored at regular intervals. Children deserve specific attention.

Reply to the letter to the editor by Papadimas et al.: "Bone mineral density in adult patients with Pompe disease" (Article)

2010-01-01T00:00:00Z

Using heparin therapy to reverse protein-losing enteropathy in a patient with CDG-Ib (Article)

2008-04-01T00:00:00Z

Background: A 22-year-old female presented with edema, diarrhea, hypoalbuminemia and pancytopenia. She had previously been diagnosed with congenital disorder of glycosylation type Ib, and had a history of congenital hepatic fibrosis, portal hypertension and esophageal varices. In the past she had refused mannose therapy because of associated diarrhea and abdominal pain. Investigations: Laboratory examinations, abdominal ultrasonography, bacterial and viral cultures of blood, urine and stools, double-balloon enteroscopy and fecal excretion test using51Cr-labeled albumin. Diagnosis: Protein-losing enteropathy. Management: Infusion of albumin followed by intravenous and subcutaneous therapy with unfractionated heparin.

Vitamin D deficiency in patients with erythropoietic protoporphyria (Article)

2008-01-01T00:00:00Z

Background: The main symptom of patients with erythropoietic protoporphyria (EPP) is painful photosensitivity, starting within minutes of sun exposure and leading to sun-avoidance. As 80-100% of vitamin D is synthesized under the influence of sunlight, we investigated whether the avoidance of sunlight exposure in the Dutch EPP patient population causes vitamin D deficiency. Furthermore, we studied the relation between vitamin D levels, total erythrocyte protoporphyrin and quality of life. Methods: In a cross-sectional study of 48 Dutch EPP patients (mean age 41.4 years; range 16-77; 23 male, 25 female), we assessed serum 25-hydroxyvitamin D (25(OH)D) levels between June and November 2007, as well as total erythrocyte protoporphyrin (TEP) levels and Dermatology Life Quality Index (DLQI) scores. Results: Mean serum 25(OH)D was 66 nmol/L (range 18-140, quartiles 36, 87). Twenty-two patients (46%; 15 male, 7 female) were vitamin D deficient. There was a significant difference (p = 0.029) in mean serum 25(OH)D between female (mean 75 nmol/L, range 18-140) and male patients (mean 55 nmol/L, range 18-115). The level of serum 25(OH)D showed a negative correlation with total erythrocyte protoporphyrin (TEP) (Pearson rank correlation (rp) = -0.337; p = 0.034). Serum 25(OH)D was inversely associated with scores of the Dermatology Life Quality Index (DLQI) (Spearman's rho correlation (rs) = -0.486; p = 0.001). Conclusions: The prevalence of vitamin D deficiency is high in the Dutch EPP population, especially in male patients, and correlates with the severity of EPP. Screening for and treatment of vitamin D deficiency should therefore be implemented in the care of these patients.

Inhibition of the renin-angiotensin system in normotensive type 2 diabetes: effects and mechanisms of action (Doctoral Thesis)

2007-04-11T00:00:00Z

The majority of clinical trials, investigating the effects of angiotensin-receptor antagonists on the diabetic kidney, have focused on hypertensive patients, thereby leaving the possibility that reduction of the systemic blood pressure explains for (most of ) the renoprotective eff ects1-5. Therefore, we studied the effects of the angiotensin-receptor antagonist losartan on urinary albumin excretion, renal function and blood pressure in normotensive patients with type 2 diabetes mellitus and microalbuminuria. The significant reduction in urinary albumin excretion rate by 35%, which we observed after 10 weeks of losartan treatment, is quantitatively comparable to the antiproteinuric effects of losartan in hypertensive diabetic patients1,2,4,6,7. In our normotensive patients, this reduction could not be explained by changes in systemic blood pressure or creatinine clearance, suggesting the involvement of other losartan-mediated mechanisms. First, antagonising the intrarenal angiotensin II leads to favorable intraglomerular haemodynamics, like reduction in arteriolar resistance and intraglomerular pressure, thereby increasing renal plasma flow, reducing the filtration fraction and thus urinary albumin excretion8,9. These changes mainly account for the early rapid component of albuminuria reduction, which parallels the time-course of changes in renal haemodynamics and is thought to be maximal within the first weeks of treatment10,11. Our results of the order of magnitude of the antiproteinuric effect after 5 respectively 10 weeks of losartan treatment, as well as the fact that urinary albumin excretion returned to pretreatment levels in the 5-week placebo washout period, are in concordance with these observations and thus probably result mostly from renal haemodynamic factors. Secondly, losartan treatment probably results in slower, non-haemodynamic renal changes as well, contributing to the well-established long-term renoprotective effects of angiotensin II antagonists in patients with diabetes mellitus3-5. These changes possibly involve improvement of endothelial function and reduction of the chronic low-grade infl ammatory state12,13. However, we have no data on this in our patient population to support this assumption in our studies. Furthermore, the interference of losartan with various growth factor systems is thought to reduce the production of extracellular matrix proteins, finally resulting in slowing down the progression of glomerulosclerosis and tubulointerstitial fi brosis14.

Effect of losartan on microalbuminuria in normotensive patients with type 2 diabetes mellitus. A randomized clinical trial (Article)

2003-01-01T00:00:00Z

BACKGROUND: Angiotensin-converting enzyme inhibitors have shown antiproteinuric effects in normotensive and hypertensive diabetic patients. Angiotensin-receptor antagonists reduce urinary albumin excretion and the risk for renal and cardiovascular complications in hypertensive patients with type 2 diabetes mellitus. The effect of angiotensin-receptor antagonists in normotensive diabetic patients with microalbuminuria has not yet been reported. OBJECTIVE: To assess the antiproteinuric effects of losartan in normotensive patients with type 2 diabetes and microalbuminuria. DESIGN: Multicenter randomized, double-blind, placebo-controlled clinical trial. SETTING: 19 outpatient clinics in the Netherlands. PATIENTS: 147 normotensive patients with type 2 diabetes mellitus and microalbuminuria. INTERVENTION: 74 patients were randomly assigned to receive losartan and 73 patients were assigned to receive placebo for 10 weeks; 71 patients in each group completed the study. The losartan dose was 50 mg during the first 5 weeks and 100 mg during the subsequent 5 weeks. MEASUREMENTS: Change in urinary albumin excretion rate after 5 and 10 weeks, change in creatinine clearance and blood pressure, and safety and tolerability of losartan. RESULTS: A significant 25% relative reduction in the albumin excretion rate occurred after 5 weeks of the 50-mg losartan dose, with further improvement over the subsequent 5 weeks with the 100-mg dose (relative reduction, 34%). In the losartan group, creatinine clearance did not improve and blood pressure decreased slightly. Side effects did not differ between treatment groups. CONCLUSIONS: The angiotensin-receptor antagonist losartan reduces urinary albumin excretion in normotensive patients with type 2 diabetes and microalbuminuria. In multivariate analysis, the antiproteinuric effect of losartan was independent of the associated reduction in blood pressure. Losartan was safe and well tolerated in these normotensive patients.