Immunoregulation with Levamisole in Children with Frequently Relapsing Steroid Responsive Nephrotic Syndrome

ABSTRACT. The immunological and clinical effects of levamisole were studied in 10 children with frequently relapsing steroid responsive nephrotic syndrome (SRNS). The efficacy of the drug was tested during remission of the disease with all patients on alternate day steroid therapy. The lymphocyte proliferative response to phytohemagglutinin (PHA), concanavalin-A (Con-A) and pokeweed mitogen (PWM) were normal. The Con-A induced suppressor T-lymphocyte activity of 7 patients was low before treatment with levamisole 8±3.7% and increased to normal values during therapy 34±6%; p <0.001 (control 32±5%). In these 7 children prednisolone dosage could be decreased significantly or discontinued altogether (44.1±5.3%). Patients without immunoregulatory abnormalities did not respond to levamisole. In 3 out of 4 children tested the percentage of OKT8⁺ cells rose during levamisole therapy from 19.7±2.1 to 37±2.3 ( p <0.001), thus correcting the elevated pre-treatment OKT4⁺/OKT8⁺ ratio from 3.1±0.2 to 1.5±0.2; p <0.001 (control 1.47±0.2). These data support the hypothesis that abnormal immunoregulation may play a role in the pathogenesis of SRNS. Treatment with levamisole can be useful in some patients with the frequently relapsing form of the disease.     

Immunologic changes in diabetic ketoacidosis]

We studied 13 children and adolescents during diabetic ketoacidosis; the duration of diabetes ranged from 1.4 to 6.0 years. A group of 13 diabetic sex, age and duration of disease-matched children served as control. Patients in ketoacidosis showed important abnormalities of T subset percentages (OKT3: 63.4 +/- 1.87% vs 72.1 +/- 3.4; p less than 0.001. OKT4: 37.18 +/- 1.85% vs 44.6 +/- 3.9; p less than 0.01. OKT8: 28.5 +/- 6.51% vs 28.1 +/- 1.9; p less than 0.04) and impaired neutrophil chemotaxis (53.10 +/- 3.3 vs 88.1 +/- 7.2; p less than 0.001). The patients showed normal levels of all classes of immunoglobulins. No correlation was observed between these abnormalities and the degree of ketoacidosis or glycaemia. When the patients were re-evaluated out of ketoacidosis, the values of the immunological parameters were normal and similar to those of the control group.     

Efficacy of levamisole in children with frequently relapsing and steroid-dependent nephrotic syndrome

Objectives

To assess the efficacy of levamisole in frequently relapsing nephrotic syndrome and steroid-dependent nephrotic syndrome.

Study Design

Retrospective analysis of hospital case records.

Setting

Pediatric nephrology department of a tertiary referral pediatric hospital.

Participants

62 children with frequently relapsing nephrotic syndrome and 35 children with steroid-dependent nephrotic syndrome.

Methods

Case records of children who were diagnosed as steroid-dependant or frequently-relapsing nephrotic syndrome from June 2004 to June 2011, were reviewed. Levamisole was given daily (2 mg/kg/d) along with tapering doses of alternate day steroids after remission on daily steroids.

Results

Levamisole was effective in 77.3% children with a better (80.6%) efficacy in frequently relapsing nephrotic syndrome. A total of 34 children completed 1 year follow-up post levamisole therapy. The cumulative mean (SD) steroid dose 1-year before therapy was 4109(1154) mg/m² and 1-year post therapy was 661 (11) mg/m² (P<0.001). The relapses were also less during the period of post-levamisole therapy.

Conclusion

Levamisole is an effective alternative therapy in frequently relapsing and steroid-dependent nephrotic syndrome.     

Levamisole in frequently-relapsing and steroid-dependent nephrotic syndrome

Objective

To evaluate the efficacy of levamisole in children with frequently relapsing nephrotic syndrome (FRNS) and steroid dependent nephrotic syndrome (SDNS) when administered on an alternate day (‘initial therapy’ in all cases) or daily basis (‘rescue therapy’ in whom alternate day therapy failed).

Methods

The records of 95 children (age 1–18y) with FRNS (62) and SDNS (33), who were treated at the Pediatric nephrology clinic, and received levamisole therapy (maximum 2 y duration, between 2010–2013) with a follow-up period of minimum 1 y, were included.

Results

Alternate day levamisole therapy was efficacious in 73.7% (n=70). The overall efficacy of levamisole therapy was 88.4% (n=84). Levamisole therapy decreased the mean (SD) number of relapses from 4.22 (0.46)/y to 1.35 (0.36)/y (P<0.01); and cumulative median (IQR) prednisolone dosage from 4200 (3200–4300) mg/m² to 1100 (IQR 500–2900) mg/m² (P<0.001). On a one-year follow up of the cases in whom levamisole therapy was efficacious during therapy (median 24 mo) (n=84), a frequently relapsing or steroid dependent course continued to persist in 48.8% (41), necessitating oral cyclophosphamide (n= 22) or mycophenolate mofetil (n=19).

Conclusions

Daily levamisole therapy was useful in 56% of children who demonstrated failure while on alternate day levamisole therapy, and could be a useful therapeutic option in FRNS and SDNS.

     

散发性激素耐药型肾病综合征患儿30例足细胞基因突变分析

目的分析散发性激素耐药型肾病综合征(SRNS)儿童足细胞基因突变及其特点。方法研究对象为30例散发性SRNS患儿和50例尿检正常的健康志愿者。采用PCR扩增NPHS1、NPHS2和CD2AP基因全部外显子及其周围的部分内含子,WT1基因外显子8和9及其周围的部分内含子;应用DNA序列直接测定法对其PCR产物进行测序。结果在10例应用激素和免疫抑制剂治疗肾病无缓解的SRNS患儿中,发现1例携带WT1基因杂合突变——1180C>T(R394W),1例携带NPHS1基因复合杂合突变——2677A>G(T893A)和*142T>C,1例携带CD2AP基因杂合突变IVS13-137G>A。在20例应用激素或免疫抑制剂治疗肾病缓解的SRNS患儿中,发现4例患儿携带NPHS1基因单杂合突变——928G>A、IVS8+30C>T、IVS21+14G>A和IVS25-23C>T,1例患儿携带CD2AP基因单杂合突变(IVS7-135G>A)。结论对激素和免疫抑制剂均耐药的SRNS患儿需进行足细胞基因突变分析。     

Efficacy of rituximab therapy in children with refractory nephrotic syndrome: a prospective observational study in Shanghai

Background

Idiopathic nephrotic syndrome is the most common glomerular disease in children. This study was undertaken to observe the efficacy and side-effects of rituximab (RTX) in treating children with different types of refractory primary nephrotic syndrome.

Methods

Twelve patients with steroid dependent nephrotic syndrome (SDNS), frequently relapsing nephritic syndrome (FRNS), and steroid resistant nephrotic syndrome (SRNS) were enrolled in our study. There were obvious drug side-effects, and proteinuria remained difficult to control. RTX was administered at a dose of 375 mg/m² body surface area, once or twice weekly.

Results

The male to female ratio was 3:1, and the onset age was 1.6–8.9 years. There were 9 patients with steroid sensitive nephrotic syndrome (SDNS or FRNS), and 3 patients with SRNS. There were 7 patients with minimal change disease (MCD), 3 patients with focal segmental glomerular sclerosis (FSGS), 1 with focal proliferative glomerulonephritis, and 1 without renal biopsy. The total effective treatment rate of RTX was 91.67%, and for 77.78% of the patients, steroid dosage could be reduced. Six months before and after RTX infusion, the mean steroid dosage was significantly decreased (P=0.014) and the recurrence number was significantly reduced (P<0.001). The results were better in MCD patients than in FSGS patients (P=0.045). There was no significant difference between FRNS/SDNS and SRNS patients (P=0.175). During RTX administration, 3 patients developed skin rashes, 1 developed hypotension, and 1 developed a fever. One patient experienced a persistent decrease in serum immunoglobulin level but without serious infection.

Conclusion

RTX was effective in the treatment of refractory nephrotic syndrome, and it could significantly reduce the use of steroid and immunosuppressants.     

Persistent hypercholesterolaemia in frequently relapsing steroid-responsive nephrotic syndrome

Objective: To investigate long-term changes of serum cholesterol levels in children with frequently relapsing steroid-responsive nephrotic syndrome (NS).
Methodology: Serum cholesterol values just before and during or immediately after 'relapse' were reviewed and the incidence of hypercholesterolaemia (≥200 mg/dL) was determined in eight patients (M:F, 6:2).
Results: The patients with frequently relapsing NS usually showed hypercholesterolaemia (mean incidence, 81%) just before 'relapse' during clinical remission, as well as in relapse (mean incidence, 96%). A high incidence of steroid therapy was also found in each case (mean, 89%) just before relapse.
Conclusions: Our results demonstrate that children with frequently relapsing NS have prolonged periods of hypercholesterolaemia, even during clinical remission. It is suggested that serum lipid profiles be monitored carefully in such patients.     

Urinary protein electrophoresis patterns in childhood idiopathic nephrotic syndrome

We investigated the utility of a standard urinary protein electrophoresis (UPEP) to distinguish among three common variants of childhood idiopathic nephrotic syndrome (NS). The UPEP was performed on 66 urine samples obtained during a disease relapse in 43 children and adolescents with idiopathic NS. There were 15 children with minimal change disease (MCD), 11 with IgM nephropathy (IGMN) and 17 with focal segmental glomerulosclerosis (FSGS). Fourteen of the 26 children (54%) with MCD or IGMN and 16/17 (94%) of the patients with FSGS manifested a frequently relapsing or steroid dependent course. The mean percent albumin and gamma globulin excretion in the UPEP in patients with MCD and IGMN were 75.5 and 2.9 versus 72.6 and 3.9, respectively (p = NS). Both patterns were significantly different from that observed in FSGS, albumin 62.2%, gamma globulin 7.1% (p less than 0.005). Although the percent gamma globulin excretion was inversely related to GFR in children with FSGS, this measurement exceeded a 4.3% cutoff in 9 of these patients while their GFR was normal (less than or equal to 80 ml/min/1.73M2). Therefore, we recommend the use of the UPEP as a marker of urinary protein selectivity and to monitor children with high-risk nephrotic syndrome i.e., those with a frequently relapsing or steroid dependent clinical course, for histological transitions.     

Treatment of idiopathic nephrotic syndrome with levamisole

Thirty children with frequently relapsing idiopathic nephrotic syndrome (INS) were treated with levamisole (2.5 mg/kg BW) twice a week for a mean period of 9.9 months. A beneficial effect was observed in 16 children in whom corticosteroids could be significantly decreased without relapse. Levamisole was ineffective in 14 patients. There was no difference between the two groups in the duration of INS, the number of relapses and the duration of treatment with levamisole. The mean age at onset of INS was higher in the group of patients where levamisole was effective (5.8 years versus 2.8 years). In 7 patients who responded to levamisole neutrophils decreased below 4 X 10(9)/l. Transient granulocytopenia was observed in 3. It is concluded that levamisole may be effective in frequently relapsing INS with minimal side effects.     

Treatment of Idiopathic Nephrotic Syndrome with Levamisole

Thirty children with frequently relapsing idiopathic nephrotic syndrome (INS) were treated with levamisole (2.5 mg/kg BW) twice a week for a mean period of 9.9 months. A beneficial effect was observed in 16 children in whom corticosteroids could be significantly decreased without relapse. Levamisole was ineffective in 14 patients. There was no difference between the two groups in the duration of INS, the number of relapses and the duration of treatment with levamisole. The mean age at onset of INS was higher in the group of patients where levamisole was effective (5.8 years versus 2.8 years). In 7 patients who responded to levamisole neutrophils decreased below 4×10⁹/l. Transient granulocytopenia was observed in 3. It is concluded that levamisole may be effective in frequently relapsing INS with minimal side effects     

Allogeneic bone marrow transplantation versus chemotherapy in children with acute leukemia in Sweden

All children in Sweden who underwent bone marrow transplantation (BMT) with an HLA-identical sibling during a 5-year period were compared to those who were treated with chemotherapy and survived at least 3 months after remission. All patients were observed for more than 2 years after diagnosis or relapse. All 11 children with acute myeloid leukemia in first remission who underwent BMT survived compared to only 1 of 15 treated with chemotherapy (p less than 0.001). In children with acute lymphoblastic leukemia (ALL), those relapsing while on chemotherapy and treated with BMT in second to fourth remission (n = 16) had a 5-year survival of 43% compared to 16% for those treated with chemotherapy (n = 53, p less than 0.05). In children with ALL relapsing after cessation of therapy, 4-year survival was 33% for BMT (n = 6) and 55% for chemotherapy (n = 15), p = 0.05).     

T cell subsets in human colostrum

Lymphocytes from 10 paired colostrum and peripheral blood specimens were examined to determine if the colostral T cell population differs from the peripheral blood T cell population in subset distribution. The percentages of lymphocytes staining with OKT3, OKT4, and OKT8 murine monoclonal antibody were determined. Lymphocytes from colostrum were 74.7 +/- 2.5% OKT3+, 50.6 +/- 2.3% OKT4+, 24.0 +/- 1.7% OKT8+, whereas peripheral blood lymphocytes were 78.7 +/- 1.9% OKT3+, 48.4 +/- 1.4% OKT4+, and 29.8 +/- 1.6% OKT8+. The percentage of colostrum lymphocytes positive for OKT3 was significantly although not strikingly lower than the OKT3 percentage for blood lymphocytes (p less than 0.05). This difference was due to the lower percentage of OKT8 positive lymphocytes in colostrum compared with blood (p less than 0.01). Although the T cell subset distribution of colostrum generally appears to be similar to that in the peripheral blood, there were small differences in OKT3 and OKT8 percentages that were statistically significant suggesting the possibility of some selectivity of the colostral T cell population.     

激素敏感型肾病综合征患儿甲基泼尼松龙冲击前后白介素13的表达

目的：观察白介素13（IL-13）在小儿类固醇敏感肾病综合征（SRNS）中的变化及甲基泼尼松龙冲击治疗（MPT）对IL-13表达的影响,探讨其在SRNS发病中的作用。方法：分别采用ELISA法及RT-PCR法测定20例正常儿童及28例SRNS患儿MPT前、结束后2 d、5 d、尿蛋白转阴后2周血清IL-13水平及外周血单个核细胞(PBMC) IL-13 mRNA水平。采用双缩脲法对SRNS患儿检测24 h尿蛋白量。结果：血清IL-13蛋白水平及PBMC IL-13 mRNA表达MPT前明显高于MPT结束后5 d组、尿蛋白转阴后2周组及正常对照组,差异有显著性（均P＜0.01）;MPT结束后5 d组较正常对照组高,差异有显著性（P＜0.05）; MPT前与结束后2 d比较差异无显著性（P＞0.05）。尿蛋白转阴后2周组血清IL-13蛋白水平及PBMC IL-13 mRNA表达与正常对照组比较无统计学意义。SRNS患儿血清中IL-13水平与24 h尿蛋白量呈正相关。结论：SRNS患儿血清IL-13及其基因表达异常,MPT对SRNS患儿IL-13在蛋白合成和基因转录两个水平上可能有抑制作用。［中国当代儿科杂志,2007,9（6）：533-536］     

Steroid resistant nephrotic syndrome: role of histopathology

This study was conducted to (1) see the histopathological distribution of different subtypes in steroid resistant nephrotic syndrome (SRNS) and (2) compare the clinical, biochemical parameters and outcome between Minimal Change Disease (MCD) with non-MCD subtypes in response to immunosuppressive therapy. A retrospective analysis was done of data on all biopsy proven children with idiopathic SRNS (no response to 4 weeks of standard prednisone therapy (60 mg/m(2)/day)) referred to our institute over last 12 years. They were treated with one of the following medications: oral or intravenous cyclophosphamide, cyclosporine or combination of dexamethasone and azathioprine. A comparison was done of the demographic clinical and biochemical features different histopathologies. We studied 136 children with SRNS (100 M, 36 F). They accounted for 15.1%(136/900) of all children with idiopathic nephrotic syndrome. Focal segmental glomerulosclerosis (FSGS) was the commonest 80/136 (59%), followed by MCD (17.6%). Children with non-MCD had a significantly greater prevalence of microhematuria as compared to MCD. The other baseline clinical and biochemical features including the glomerular filtration rate (GFR) were similar. After a mean follow up of 46 (8-148) months, a significantly greater children with non-MCD 65/112) continued to be proteinuric as compared to the MCD (3/24) (p=0.0001). FSGS was the commonest cause of SRNS in our patient population. Children with SRNS secondary to MCD are more likely to achieve remission as compared to non-MCD subtypes and have a better long-term prognosis. Hence kidney biopsy is of significant prognostic value in SRNS.     

Comparison of different regimens of prednisone therapy in frequently relapsing nephrotic syndrome

The long-term results of four different regimens of prednisone therapy were compared in 32 children with steroid sensitive, frequently relapsing idiopathic nephrotic syndrome with minimal glomerular lesions on renal biopsy. Prednisone was administered according to the following dosage schedules: 1) long-term daily, 2) standard intermittent, 3) standard alternate-day, and 4) short-term daily. Over a mean observation period of 7 years patients without steroid dependency received 19 mg/m2/day. Relapse free intervals were the longest with long-term daily prednisone therapy compared to the other three regimens. In frequently relapsing patients without steroid dependency the relapse free intervals were similar with either intermittent or alternate-day prednisone therapy (median 75d); however, they were significantly shorter with short-term prednisone therapy (median 33d). In frequently relapsing patients with steroid dependency the time of remission was generally shorter than in patients without steroid dependency (median 25d vs. 69d) with no benefit of any of the different forms of short-term treatment.     

Assessment of glycemic control by continuous glucose monitoring system in 50 children with type 1 diabetes starting on insulin pump therapy

OBJECTIVE: To report experience with a continuous glucose monitoring system (CGMS) and to identify factors influencing glycemic control in a large cohort of children and adolescents with type 1 diabetes and change to insulin pump therapy via continuous subcutaneous insulin infusion (CSII). RESEARCH DESIGN and METHODS: In 50 patients [21 boys, 29 girls; median age 12.6 yr (range: 1.3-16.4 yr); diabetes duration 5.0 yr (0.2-13.3)], hemoglobin A1c (HbA1c) and ambulatory CGMS were performed before and 6 wk after starting CSII. Average glucose concentration per 24 h, during day and night time as well as number of excursions, duration, and area under the curve (AUC) of glucose values above 180 mg/dL and below 60 mg/dL were calculated from CGMS data. Simultaneously, metabolic control was documented by standardized self-monitoring of blood glucose (SMBG). RESULTS: In the total cohort, HbA1c improved from 8.1 +/- 1.2% at baseline to 7.7 +/- 0.9% after 6 wk of CSII (p <0.001). This effect was more distinct in boys (8.0 +/- 1.4 vs. 7.5 +/- 1.1%, p=0.007) than in girls (8.1 +/- 1.1 vs. 7.8 +/- 0.7%, p=0.039) as well as in patients with poor glycemic control (HbA1c >8.0%) at baseline (8.9 +/- 0.6 vs. 8.1 +/- 0.8%, p <0.001) and in those older than 12 yr (8.2 +/- 1.2 vs. 7.7 +/- 1.0%, p <0.001). At 6 wk of CSII, the values of glucose average per 24 h, AUC and time above 180 mg/dL, particularly during the day, improved. HbA1c was correlated with AUC above 180 mg/dL (r=0.742, p <0.001) and CGMS average glucose per 24 h (r=0.628, p=0.002), but to a lesser extent with SMBG values (r=0.418, p=0.054). CONCLUSION: With the change to CSII, HbA1c improved significantly after 6 wk of therapy. CGMS usage provided additional information about glycemic control in these patients.     

Utility of breath ethane as a noninvasive biomarker of vitamin E status in children.

The purpose of our study was to determine if the ethane content of expired air could be a useful index of vitamin E status in children. Eight children with vitamin E deficiency secondary to chronic severe liver disease were studied: six of these children were treated with parenteral vitamin E (2-5 mg/kg/dose every 4-7 d). Measures of vitamin E status pre- and posttherapy were: serum vitamin E, 2 +/- 1 versus 7 +/- 1 micrograms/mL (p less than 0.001); serum vitamin E:total lipids, 0.3 +/- 0.1 versus 1.0 +/- 0.1 mg/g (p less than 0.001); and erythrocyte peroxide hemolysis test, 80 +/- 10 versus 6 +/- 12% (p less than 0.001). Fasting breath ethane in the patients pre- and posttherapy was 78 +/- 10 versus 31 +/- 11 pmol/kg/min (p less than 0.001). Breath ethane correlated negatively with serum vitamin E (p less than 0.042) and serum E:total lipids (p less than 0.004) and positively with the erythrocyte peroxide hemolysis test (p less than 0.003). Values for treated patients did not differ from those for fasted sibling controls (34 +/- 12 pmol/kg/min), postprandial sibling controls (31 +/- 12 pmol/kg/min), and healthy children sampled randomly, in the nonfasted state (21 +/- 14 pmol/kg/min). Breath ethane production in one patient (up to 168 pmol/kg/min) did not normalize after treatment of vitamin E deficiency until her selenium deficiency was corrected as well. We conclude that this noninvasive test can be useful as a screen for vitamin E deficiency in children and for ascertaining response to therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early discontinuation of steroids is safe and effective in pediatric kidney transplant recipients

In pediatric kidney transplantation, steroid induced growth retardation and cushingoid features are of particular concern. In children, gradual steroid withdrawal late after kidney transplantation increases the risk of rejection. In this pilot study, we investigated the outcome of pediatric renal transplantation with an early steroid withdrawal protocol. This is a retrospective case-control study of pediatric renal transplants with age-matched historical control. Groups were comparable in terms of HLA matching, donor type and graft ischemia time. In the steroid withdrawal group (SWG, n = 13), induction therapy included mycophenolate mofetil (MMF) and a 5-day course of steroids with Thymoglobulin in 11 and basiliximab in two other patients. In the steroid group (SG, n = 13), in addition to steroids, four patients were given basiliximab, eight were given Thymoglobulin, and one OKT3. Maintenance therapy included tacrolimus (SWG n = 11, SG n = 3) or cyclosporine (SWG n = 2, SG n = 10). Azathioprine was given to all the patients in the SG, except the last two patients of this series who were prescribed MMF. MMF was given to all in the SWG. Patient and graft survival rates were 100% in both groups. In the SWG, no acute rejection episode was detected. In the steroid group, three patients (25%) presented with an acute rejection episode. All but one patient in either group showed immediate graft function. Patients in the steroid-withdrawal group exhibited a significantly higher creatinine clearance at 6 and 12 months post-transplant (95.8 +/- 23.3 vs. 71.3 +/- 21.9, p = 0.03; and 91.3 +/- 21.6 vs. 69.6 +/- 28.6, p = 0.04). In the SWG delta BMI was significantly lower and delta height Z score was significantly higher, and we observed significantly less hyperlipidemia, body disfigurement, and need for anti-hypertensive medication. Early steroid withdrawal in pediatric renal transplant recipients is efficacious and safe and does not increase risk of rejection, preserving optimal growth and renal function, and reducing cardiovascular risk factors.     

Major histocompatibility complex antigens and immune mechanisms in steroid-responsive nephrotic syndrome

Although the pathogenesis of steroid-responsive nephrotic syndrome (SRNS) is obscure, involvement of an immune mechanism is often suggested. Further evidence of an immune basis for this disorder is an increased frequency of specific major histocompatibility complex (MHC) antigens. In the first part of this study, the phenotypic frequency of HLA-A, -B, -C, -DR antigens were investigated in 30 children with SRNS and in 630 controls. In the second part, total T (CD3⁺ cells) and B lymphocytes (CD19⁺ cells) and the lymphocyte subsets (CD4⁺, CD8⁺ cells and their ratio) were studied in the same patients and in 30 healthy children. The investigations of all the patients were performed during the acute stage and 14 of 30 during remission stage. Human leukocyte antigens (HLA) were determined by standard microlymphocytotoxicity assay and lymphocytes were analyzed by flow cytometry. Human leukocyte antigens A3, DR4, DR7 and the haplotype HLA-A2/B12 showed the strongest association with SRNS. In the studies for cellular immune disorder, CD3⁺ and CD8⁺ cells were found to be decreased significantly in the acute stage before beginning steroid therapy. No significant difference in lymphocyte subsets was observed in the remission stage without steroid or immunosuppressive therapy.     

Low bone mass in prepubertal children with thalassemia major: insights into the pathogenesis of low bone mass in thalassemia

OBJECTIVE: Low bone mass occurs frequently in the aging thalassemic population. However, limited information exists on bone mass in children with thalassemia major (TM) during their first decade of life. STUDY DESIGN: Spinal bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXA) in 18 children (age 5.8 +/- 1.5 yr; M:F 8:10) with TM on hypertransfusion and iron chelation therapy. Serial BMD measurements were available for 11 of the 18 children. RESULTS: Weight and height z scores were 0.81 +/- 4.2 and -0.47 +/- 1.7 respectively. At the first BMD, four (22.2%) patients presented with BMD z scores less than -2.5, seven (38.8%) had BMD z scores between -1 and -2.5, while the remaining seven (38.8%) had normal BMDs (z score above -1). The mean decline of BMD z score was -0.38/year (p = ns). BMD z scores correlated with height z scores (p = 0.039), but not with liver enzymes, serum ferritin levels, or thalassemia genotypes. CONCLUSIONS: Low bone mass is present in most children with TM despite hypertransfusion and optimal chelation, adequate growth and lack of endocrine complications.