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Growth of children with β-thalassemia major
Abstract
Hypertransfusion and regular chelation therapy have allowed improved survival in patients with thalassemia major (TM). Despite
medical advances, growth failure and hypogonadism remain significant clinical problems in these patients in adolescence. Disproportionate
truncal shortening which is common especially among adolescents with thalassemia, is due to platyspondyly resulting from a
combination of factors like hemosiderosis, desferrioxamine toxicity or deficiency of trace elements. Although growth hormone
(GH) deficiency and GH neurosecretory dysfunction have been described in TM patients, most short TM patients have normal GH
reserve. The low serum IGF-1 and IGFBP-3 concentrations in TM patients despite having normal GH reserve and serum GH binding
protein levels suggest that a state of secondary GH insensitivity exists. The pubertal growth spurt may be impaired in TM
patients going through spontaneous or induced puberty and may have a negative effect on final adult height. GH therapy in
dosages ranging from 0.5–1.0 IU/kg/wk has resulted in a significant improvement in growth velocity in short TM children without
any adverse effects on skeletal maturation, blood pressure, glucose tolerance and serum lipids. There is limited evidence
that GH treatment can result in an improved final adult height in short TM children. Careful and regular clinical and biochemical
monitoring should be preformed on these patients while they are treated with GH.
... This helps to avoid developmental problems, organ damage, and abnormalities in the bones 8,9 . On the other hand, repeated blood transfusions induce iron overload, which leads to a variety of consequences such as endocrinopathies 10,11 , stunted growth 12 , cardiovascular issues 13 , liver diseases 14 , gonadal malfunction, delayed puberty 15 , and an increase in the risk of infections transmitted by transfusion 16 . As a result of the combination of frequent blood transfusions and chelation treatment, individuals are now living into their fourth or fifth decade of life. ...
... According to the age wise distribution, 23 (15.33%) of the patients belong to age group (0-5) years, 40 (26.67%) patients in the age group (6-10) years, 49 (39.33%) of the patients belong to age group (11)(12)(13)(14)(15) years, 27 (18%) patients in the age group (16)(17)(18)(19)(20) years while 11 (7.33%) patients were recorded in the age group ˃20. (Figure 2) Amongst 150 beta-thalasemic patients, 122 (81.33%) patients were observed having dermatological problems. ...
Background: Beta-thalassemia is the world's most prevalent single-gene disease with a reduction in the synthesis of hemoglobin b-chain. A lot of skins problems occur in thalassemia patients but, no study have been conducted in Pakistan to determine their prevalence. Objective: To determine the prevalence of dermatological problems in beta-thalasemic patients Methodology: This was cross sectional study carried out at the department of dermatology Al-Khidmat hospital Peshawar for a period of one year from August 2020 to August 2021. All the beta-thalassemia patients were examined for dermatological problems by a single expert dermatologist. All of the data was entered and analyzed by using the SPSS version 20 software. Results: Amongst 150 beta-thalasemic patients, 122 (81.33%) patients were observed with dermatological problems. The most frequent dermatological problem observed in our study was pruritus in 54 (36%) patients followed by xerosis in 34 (22.67%), urticaria in 30(20%), Pigmentary disorders in 33(22%) patient, freckles in 24(16%), tinea infections in 15(10%), pitriasis alba in 13 (8.67%) patients, scars in 13 (8.67%), hypersensitivity to deferoxamine pump in 12 (8%), herpes simplex in 12 (8%), Verruca vulgaris in 10 (6.67%), acne in 8 (5.33%) patients, miliaria in 8 (5.33%) while contact dermatitis was observed in 6(4%) of the patients. Conclusion: Our study concludes that dermatological problems are highly prevalent in beta-thalassemia patients with pruritus as the most common problem followed by xerosis. Keywords: Prevalence; Dermatological problems; Beta-thalasemia; Pruritus; Xerosis.
... However, one of the causes is the shortening of patients' trunks disproportionately due to delayed-chelating therapy and hypogonadism [93]. The pituitary gonadotropes are incredibly vulnerable to oxidative stress caused by iron deposition in the hypothalamus and pituitary gland [9]. De Sanctis et al. evaluated the prevalence rate of ST among 3023 βTM patients in 16 countries and reported that 53% were short. ...
... Yassin suggests that the higher deposition of iron in the liver, the higher prevalence of complications like GHD [8]. Also, an increase in the somatostatinergic tone on GH release justifies impaired GH secretion [9]. GHD is also affected by increasing hypothyroidism and delayed puberty. ...
Background:
Blood transfusion is a traditional treatment for β-thalassemia (β-thal) that improves the patients' anemia and lifespan, but it may lead to iron overload in parenchymal tissue organs and endocrine glands that cause their dysfunctions as the iron regulatory system can't excrete excess iron from the bloodstream.
Objective:
To evaluate the prevalence of iron-related complications (short stature, growth retardation, and growth hormone deficiency) in β-thalassemia major (βTM) patients.
Methods:
We performed an electronic search in PubMed, Scopus, and Web of Sciences to evaluate the prevalence of growth hormone impairment in β-thalassemia major (βTM) patients worldwide. Qualities of eligible studies were assessed by the Joanna Briggs Institute checklist for the prevalence study. We used Comprehensive Meta-Analysis (Version 2) to calculate the event rate with 95% CIs, using a random-effects model for all analyses.
Findings:
Seventy-four studies were included from five continents between 1978 and 2019; 70.27% (Asia), 16.21% (Europe), 6.75% (Africa), 2.70% (America), 1.35% (Oceania), and 2.70% (Multicenter). The overall mean age of the participants was about 14 years. The pooled prevalence of short stature (ST) was 48.9% (95% CI 35.3-62.6) and in male was higher than female (61.9%, 95% CI 53.4-69.7 vs. 50.9%, CI 41.8-59.9). The pooled prevalence of growth retardation (GR) was 41.1% and in male was higher than in female (51.6%, 95% CI 17.8-84 vs. 33.1%, CI 9.4-70.2). The pooled prevalence of growth hormone deficiency (GHD) was 26.6% (95% CI 16-40.8).
Conclusion:
Our study revealed that near half of thalassemia patients suffer from growth impairments. However, regular evaluation of serum ferritin levels, close monitoring in a proper institute, suitable and acceptable treatment methods besides regular chelation therapy could significantly reduce the patients' complications.
... To sustain children affected with βthalassaemia, monthly blood transfusions accompanied by iron chelation therapy is needed, and requirements for treating one annual birth cohort for one year are 90,000 units of blood plus 22 million dollars' worth of deferoxamine 14,17 . Many studies concluded that cirrhosis of liver is associated with increase in serum ferritin level [16][17][18][19][20][21] . ...
Objective: To compare the mean serum ferritin levels in thalassaemia major patients after giving deferasirox and deferoxamine. This is a randomised control trial conducted at the Department of Paediatrics, Civil Hospital, Karachi from 29th January 2014 to 28th July 2014. Methods: A total of 160 patients of either gender, with age between 1 to 14 years, who received blood transfusion at least once a month for one year and had serum ferritin >1000 mcg/L were included. Each enrolled patient was randomly allocated to group-A (deferoxamine) or group-B (deferasirox). Pre- and post-treatment iron profile was done in both groups to assess the iron status in the body. De- scriptive statistics were applied to calculate mean and standard deviation for the quantitative vari- ables. Frequencies and percentages were calculated for the qualitative variables. Independent sample t-test was applied to compare mean change in serum ferritin level in both groups. Effect modifiers were controlled by stratification. Paired t-test was also applied post stratification and p- value £ 0.05 was considered as significant. Results: Overall there were 96 male and 64 female patients. The overall mean age of study subjects was 7.54 ± 4.21 years. In the deferasirox group, mean age was 6.35 ± 4.11 years, mean weight wasv18.01 ± 6.74 kg, mean height was 102.04 ± 19.48 cm, and mean duration of transfusion was 7.48 ± 3.99 months/year. In the deferoxamine group, mean age was 8.74 ± 3.97 years, mean weight was 20.44 ± 6.77 kg, mean height was 102.19 ± 20.85 cm, and mean duration of transfusion was 8.14 ± 3.55 months/year. In the deferasirox group, before treatment mean serum ferritin level was 1385.73 ± 117.01 mcg/L. After treatment mean serum ferritin level was reduced to 1047.59 ± 117.08 mcg/L. In the deferoxamine group, before treatment mean serum ferritin level was 1362.58 ± 134.42 mcg/L. Af- ter treatment mean serum ferritin level was reduced to 1124.36 ± 134.52 mcg/L. Post-treatment the serum ferritin level between two groups was significantly different with p<0.01. The mean difference in serum ferritin level in pre- and post-treatment among two groups was highly significant with p<0.01. Conclusion: Deferasirox is an effective, safe and tolerable chelation therapy for the treatment of thalassaemia major with iron overload due to its ability to provide constant chelation coverage and potential to improve compliance.
... mg of iron/kg/day. [2][3][4][5][6] In majority of cases, the chronic growth retardation of thalassemia major patients resulted by tissue hypoxia and iron toxicity. ...
Background: Ineffective erythropoiesis and excessive red blood cell transfusions are the major source of iron overload in case of thalassemia major patients. It is mainly accountable for the growth retardation, morbidity, and mortality in patients with beta thalassemia major. The availability of effective iron chelators and proper knowledge regarding the iron toxicity can significantly improve the rate of survival in thalassemia patients.
Aims and Objectives: The study was done to compare the efficacy and safety of the deferiprone (DFP) with deferasirox (DFX) in regulating the growth pattern among the thalassemia major patients.
Materials and Methods: The height and weight were plotted on the World Health Organization recommended growth charts for 0–5 years and 5–19 years old boys and girls during the follow-up visits. Comparison between the role of DFP versus DFX was evaluated by t-test.
Results: There is no statistically significant (P=0.11 in males and P=0.06 in females) difference between DFP versus DFX while considering height velocity. A similar observation was obtained in case of weight velocity (P=0.78 in males and P=0.56 in females) and basal metabolic index (BMI) index (P=0.44 in males and P=0.53 in females).
Conclusion: Both DFX and DFP have no significant correlation in regulating the height, weight, and BMI of thalassemia children.
... Thalassemia are defined as a group of inherited hematological disorders characterized by early onset of anemia resulting from reduced rate of synthesis of one or more globin chains caused by globin chain mutations (Low, 2005). I IJSER Thalassemias are the commonest monogenic syndromes (Thein, 1992), characterized by decreased synthesis of one or the other polypeptide chains resulting by decreased intracellular heamoglobin content (hypochromia) and small size of red cells (microcytosis). ...
Thalassemia are defined as a group of inherited hematological disorders characterized by early onset of anemia resulting from reduced rate of synthesis of one or more globin chains caused by globin chain mutations. The present study was designed to find out the occurrence and comparison (prevalence) of beta thalassemia major in the population of Urban (Mingora) and Rural (tehsil Kabal) localities of District Swat. Occurrence of thalassemic patients in both the localities were categorized, regarding three aspects i.e. age wise, gender wise and blood group wise. It was also examined to test out if there is any correlation of blood group with the disease or not? Prevalence ratio of both the localities was also determined. Data of patients was collected from Wajeeha thalassemia Center Swat and Alfajr Foundation Swat. In the total population of 440000 persons of Mingora, 35 (0.008%), while in that of 170000 population of tehsil Kabal 42 (0.024%) registered patients were reported. Out of all these 70 patients, 40 (51.94%) were male while 37 (48.05%) were female. 24 (31.16%) were in age group 1-5, 25 (32.46%) in age group 6-10, 17 (22.7%) in 11-15, 08 (10.38%) in 16-20 and 03 (03.89%) were in age group 21-25. There were no patients above the age of 25. In blood group wise distribution, as Rh positive blood group occur 85% in nature, so the individuals having these group in our data were examined to be 74 out of 77 in which A+ were 22 (31.42%), no one in A-, 26 were B+ (33.76%), one was B-(01.29%), 3 were AB+ (03.89%), no one in AB-, 23 were O+ (29.87%) and 2 were O-(02.59%). This shows that there is no correlation of the disease with blood group. The recent study will provide reports and recommendations to the concerned field and will make awareness of beta thalassemia major disease among patients and public for their safety. Moreover, same study should be conducted in large population size to determine the other risk factors.
... Beta thalassemia major is caused by complete absence of beta globin chain production resulting from reduced synthesis of one or more globin chains which can be caused by different globin gene mutation resulting in ineffective hematopoiesis, increased hemolysis and early onset anemia. [1][2] It has been estimated that the prevalence of pathological hemoglobinopathies in India is 1.2/1,000 live births, and with approximately 27 million births per year this would suggest the annual birth of 32,400 babies with a serious hemoglobin disorder. Reportedly, there are about 240 million carriers of β-thalassemia worldwide, i.e. 1.5% of world population. ...
Background: To study lipid profile in Beta-Thalassemia Major Patients. Methods: A cross-sectional was done on 30 diagnosed Cases of beta-thalassemia major in the age group of 1 year to 18 years receiving regular blood transfusions; not suffering from any ailment or any other disease leading to deranged lipid profile were included. Results: Lipid analyses of controls and thalassemic children. It is clear from the results that beta thalassemia major patients had significantly lower total cholesterol (TC), high-density lipoprotein cholesterol (HDL) and low-density lipoprsotein cholesterol (LDL) compared with controls. Conclusion: Lipid profile in Beta thalassmia patients show significantly low levels of total cholesterol, LDLC and HDL-C. Keywords: Beta Thalassemia Major, Lipid Profile, LDL, HDL.
... 27 The increased serum ferritin level could be contributed to multiple life-long transfusions and enhanced iron absorption results in secondary hemosiderosis. 28 Studies have revealed that thalassemic children had significantly higher serum ferritin levels compared with the controls. No significant difference was found in serum ferritin between thalassaemia major and thalassaemia intermedia. ...
Objectives: The aims is to determine whether there is any difference between thebone age of thalassemic children with chronological age and serum ferritin and its correlationwith normal children of the same age. Study design: This was cross sectional analytical study.Place & Duration: The study was conducted as age sex matched normal control, from Fatimidand Khyber Teaching Hospital Peshawar during August 2014 to January 2015. Material &Methods: A total 156 samples were selected conveniently to make comparison of bone agebetween thalassemic children (age 9-15years) and control. A structure data collection check listwas used to collect data X-ray findings (bone age) and Ferritin level. Data were analyzed usingSPSS version 20 and MS Excel. The frequency, proportion, percentages, ratio, means and SDwere calculated. Student’s t- test was applied to compare the means of biochemical measuresbetween the two groups, P value ≤ 0.05. Results: The results indicate total 156 children wereincluded with mean age 11.9 ± 2.2, {97(62.2%) were being males and 59 (37.8%) were beingfemales}. Out of thalassemic (n= 76) majority 49 (62.8%) were male as compare to female29(37.2%). The bone age was significantly different from control (p = 0001). Similarly the meanferritin concentrations were also different (P = 0001). Conclusion: Serum ferritin level could beone of the indictors for osteoporosis and thus may play an imperative role in the managementof thalassemia patients by early diagnosis and treatment.
... Certain communities in India, like Sindhis, Guajarati's, Punjabis, and Bengalis, are more commonly affected with beta thalassemia, the incidence varying from 1 to 17%. [1][2] It has been estimated that the prevalence of pathological haemoglobinopathies in India is 1.2/1,000 live births, and with approximately 27 million births per year this would suggest the annual birth of 32,400 babies with a serious hemoglobin disorder. Reportedly, there are about 240 million carriers of β-thalassemia worldwide, i.e. 1.5% of world population. ...
Background: Beta-thalassemia is the commonest single-gene disorder in the Indian population. Beta thalassemia major is caused by complete absence of beta globin chain production resulting from reduced synthesis of one or more globin chains which can be caused by different globin gene mutation resulting in ineffective hematopoiesis, increased hemolysis and early onset anemia. Methods: A cross-sectional; case control study was done on 50 diagnosed Cases of beta-thalassemia major in the age group of 1 year to 18 years receiving regular blood transfusions; not suffering from any ailment or any other disease leading to deranged lipid profile were included. In controls; 50 normal healthy children were included. Results: Lipid analyses of controls and thalassemic children. It is clear from the results that beta thalassemia major patients had significantly lower total cholesterol (TC), high-density lipoprotein cholesterol (HDL) and low-density lipoprsotein cholesterol (LDL) compared with controls (p<0.001). Conclusion: Lipid profile in Beta thalassmia patients show significantly low levels of total cholesterol, LDLC and HDL-C. Keywords: Beta Thalassemia Major, Lipid Profile, Hypocholesterolemia.
Hemosiderosis, or iron overload, is a pathological condition characterized by deposition of excess iron within the body tissues that normally do not contain iron. Hemosiderosis is usually secondary to a primary cause such as multiple blood transfusion, chronic hemodialysis, or hemolytic anemia (e.g., thalassemia).KeywordsMultiple myelomaSickle cell diseaseFamilial Mediterranean feverPernicious anemiaMycosis fungoides
Objective: To evaluate current chelation in thalassaemia major patients. Design: It is a retrospective study. Place and duration of study: This study was conducted at Sundus Foundation, Shadman, Lahore Pakistan from March 2006 to August 2006. Subjects and, Methods: One hundred and seventy patients with transfusion dependent thalassaemia major were evaluated for chelation practice and iron overload. Results: 98.2% were found to be either non-chelators or inadequate chelators whereas 82.3% patients had serum ferritin levels above 2500 ng/ ml. Growth failure and hepatosplenomegaly were also common. Survival appears to be limited as only 6 patients were older than 20 years. Conclusion: Patients, face risks and complications during treatment of thalassaemia major. Urgent and effective measures should be taken to remove the obstacles for improvement in quality of life in these patients. Involvement of physicians about current concepts in treatment of thalassaemia major can produce promising results.
• Growth, sexual development, and hypothalamic-pituitary-gonadal function were evaluated in 23 patients with thalassemia major (14 female and nine male) aged 13 to 29 years. Five women (group 1) with hemoglobin levels of less than 7 g/dL, which were maintained by transfusions during childhood, did not spontaneously enter puberty. They had evidence of severe hypothalamic-pituitary dysfunction. Maintaining hemoglobin levels of about 8 g/dL resulted in spontaneous onset of puberty in seven of nine female patients (group 2), but had no such ameliorative effect on the nine male patients. In the latter, peak luteinizing hormone (LH) responses to gonadotropin releasing hormone correlated with bone age. Treatment with testosterone produced inconsistent partial inhibition of LH and follicle-stimulating hormone (FSH) responses to stimulation. After discontinuation of testosterone treatment, a rebound of basal testosterone, LH, and FSH levels was observed, but this was not sustained. These findings are compatible either with dysfunction of hypothalamic maturation or with partial pituitary dysfunction. Four of the group 1 females and six of the males treated with appropriate sex hormones showed satisfactory pubertal progression. Acceleration in linear growth was observed in four of the male patients whose epiphyses were still open. Treatment was well tolerated in all patients.
(Arch Intern Med 1984;144:2341-2346)
OBJECTIVE Thalassaemia major Is a common and serious medical problem, worldwide. However, there are few data concerning the various endocrine disorders which occur in this condition. We have surveyed 25 Italian centres in order to establish the prevalences and times of onset of endocrine disorders In patients with β-thalassaemia major.
PROJECT AND PATIENTS A questionnaire specifically designed to investigate the prevalences of endocrinopathles was sent to 25 paediatric and haematology departments. The following data were recorded in the questionnaire: sex, age, height and weight, pubertal status according to Tanner's classification, history of secondary amenorrhoea, type of endocrinopathy and hormone levels at diagnosis, associated complications, serum ferritin level, liver enzymes (ALT) and compliance with treatment.
RESULTS An analysis of data from 1861 patients showed that failure of puberty was the major clinical endocrine problem and was present in 51 % of boys and 47% of girls, all over the age of 15 years. Secondary amenorrhoea was recorded in 23% of patients (mean age 18.3 years), primary hypothyroidism in 6.2% (mean age 15.8 years), insulin dependent diabetes mellitus in 4.9% (mean age 18.1 years) and hypoparathyroidism In 3.6% of the patients (mean age 18.7 years). At present, the ma|orlty are in the second or third decades of life. The prevalences of hypothyroidism, insulin dependent diabetes mellitus and hypoparathyroidism differed in the various centres, whereas the frequency of pubertal disorders was very similar.
CONCLUSIONS Our study has demonstrated several points. Endocrine evaluation in thalassaemic patients must be carried out regularly, especially in those patients over the age of 10 years with Iron overload and poor compliance with chelation therapy.
The prevalences of some complications, such as insulin dependent diabetes and hypothyroidism, were lower than previously recorded. Hence, It is to be hoped endocrine complications will be less common In the future, for patients who have started chelation therapy during the first years of life.
Because of the improved survival of thalassaemic patients with insulin dependent diabetes, and the high Incidence of multiple endocrine complications, ft is important to carry out careful follow-up studies for the early detection of any other associated complications to facilitate correct treatment.
OBJECTIVE: To determine by measuring sitting and standing height, whether growth failure in homozygous β-thalassemia is disproportionate.
OBJECTIVE The clinical picture of thalassaemia major has changed progressively over the years. Our study is a retrospective analysis of data on growth in a group of patients who have completed puberty spontaneously and have attained their adult height. Our objective was to evaluate the effect of different transfusion regimes and desferrioxamine administration on the growth pattern in β thalassaemia major.
DESIGN AND PATIENTS We studied 64 patients (28 males and 36 females). The patients were divided into three groups (A, B and C) according to the different transfusion regimes and the schedules of chelating therapy. Group A consisted of 16 patients who were transfused regularly at low haemoglobin levels (on average 8 5 g/dl) from an early age and started subcutaneous chelation therapy during adolescence. Group B consisted of 19 patients who were transfused regularly at high haemoglobin levels (on average 10 g/dl) from an early age and started subcutaneous therapy during childhood. Group C consisted of 29 patients who were transfused regularly at high haemoglobin levels (on average 10-5 g/dl) from an early age and started subcutaneous chelation therapy very early, at a mean age of 2 years. Standard auxological measurements were made at 3-monthly intervals throughout childhood and puberty until adult height was achieved. For group C patients the data on linear growth are provided only until the age of 12 years.
RESULTS Our study indicates that group A male and female patients did not grow significantly better than those in group B. Group C male and female patients, surprisingly, grew no faster than those who started chelation therapy late in childhood (group A). The most striking feature in the majority of both group A and B patients was reduced spurt in height at puberty. In addition, in both groups, a reduced sitting height due to spinal growth abnormality was found. An inverse correlation between sitting height and serum ferritin levels was observed in group A patients (r=–055, P<0 05), whereas there was a direct correlation in group B patients (r= 0 42, P< 0.05).
CONCLUSIONS These data suggest that an ideal therapeutic regime has yet to be found which avoids the toxic effect of iron overload and on the other hand avoids interference with growth, secondary to desferrioxamine. Therefore we recommend that the growth of thalassaemia patients be monitored routinely at every follow-up visit and documented on growth velocity charts in order to detect early changes in their growth pattern and to establish an appropriate protocol for investigation and treatment.
The hypothesis of a defect in growth hormone (GH) binding has been suggested to explain the growth failure of thalassemic children. We have measured GH binding sites in membrane fractions prepared from liver biopsies. 6 girls and 11 boys with thalassemia major, aged 3 to 15, all prepubertal, were studied at the time of splenectomy. A liver biopsy was performed for histological studies. Part of it (about 500 mg wet weight) was used to prepare a microsomal membrane fraction. Specific binding of 125I-hGH (human GH) expressed in percentage of total radioactivity per mg membrane protein ranged from 4 to 51%. Activities of 2 other membrane markers varied much less than hGH binding: the range of insulin binding was 93-179% of total radioactivity per mg membrane protein and the ratio hGH binding/5'nucleotidase activity varies in the same proportion (10 fold) as does the binding of hGH. Histological hepatic changes were assessed with respect to siderosis, fibrosis, inflammation and necrosis. No correlation was found between these parameters and hGH binding. All patients had retarded growth (mean SDS of -2.6) and no relationship was found between the growth failure and the level or hGH binding. Maximum plasma GH peak during 2 pharmacological tests was normal in 13 children, low in 2, not obtained in 2. Plasma IGF-1 levels were low (mean 170±36 mu/ml). In conclusion: 1) Specific hGH binding to liver microsomal membranes was observed and showed Creat variations; 2) Insulin and hGH binding to liver membranes do not show parallel changes, which suggests that possible membrane alterations are not the only reason for the variations in hGH binding: 3) Plasma IGF-I levels were not related to GH binding. Thus, a defect in GH binding to liver membranes is probably not the main cause for the growth retardation of thalassemic children.
We reviewed the linear growth and growth plate morphology in all children with homozygous [beta] thalassemia followed in Toronto, for whom monthly height percentiles were available before, and for a 36-month period after, the initiation of nightly subcutaneous deferoxamine therapy. All patients were <7 years of age when begun on deferoxamine, and had received nightly deferoxamine for a minimum of 36 months. Marked abnormalities of the metaphyseal growth plate were readily observed in the distal ulnar, radial, and tibial metaphyses in 11 of 37 patients in whom a significant decline in mean height percentile was also noted. (In 10 of these 11 patients, height was less than the 15th percentile after 36 months.) These 11 patients had received a significantly greater (p < 0.025) initial and average daily dose of deferoxamine, and had maintained a significantly lower (p < 0.025) mean serum ferritin concentration over the 36 months, than the remainder of the cohort. To determine whether deferoxamine played a causative role in growth failure, growth in patients who began deferoxamine before the age 2 years was compared to that of patients who began after age 5 years, for the period between 2 and 5 years of age. Only patients begun on deferoxamine prior to age 2 years demonstrated a significant (p < 0.01) decline in height percentile by the third year, implicating deferoxamine therapy as the cause of growth failure. We conclude that both the decline in height percentile and the bony changes observed in well-chelated patients are directly related to deferoxamine therapy. They can be observed even in older patients begun on deferoxamine as late as 5 years of age, with significant declines in serum ferritin over a short period of time, and are not confined to those begun in infancy on nightly deferoxamine. These changes may result from a direct toxic effect of deferoxamine. They may, alternatively or in addition, be due to chelation of other trace minerals required for normal growth, although serum levels of several trace elements tested were normal. Serial radiographs of the radii and femurs in thalassemic patients on deferoxamine may demonstrate early metaphyseal changes. Observation of these abnormalities should be followed by reduction of the nightly dose of deferoxamine to the lowest level that results in negative iron balance, and growth velocity should be observed carefully, in parallel with regular follow-up of bone abnormalities.
(C) Lippincott-Raven Publishers.
To evaluate the growth hormone reserve and the growth hormone response to recombinant human growth hormone (GH) in prepubertal thalassemic children with growth retardation.
Twenty thalassemic patients with short stature and delayed bone age were studied. Patients were randomized into GH-treated (n = 10) and non-GH treated (control; n = 10) groups. The GH-treated group received recombinant human (rh)-GH (Genotropin) at the dose of 0.7 IU/kg per week for 12 months.
There was a significant discordance between GH response to pharmacologic stimuli and physiological secretion of GH/GHRH testing. Following the administration of rhGH, growth velocity increased from 2.47 +/- 0.48 cm/year to 6.27 +/- 0.76 cm/year (P = 0.005), whereas there was not a similar change in the non-GH-treated group. The height velocities of the two groups during the 1 year follow-up period were significantly different (6.27 +/- 0.76 vs 3.99 +/- 0.34 cm/year; P = 0.025). There were significant differences between the height velocity improvements and height velocity standard deviation scores of the two groups as well.
The present study has demonstrated that rhGH is a safe and efficacious mode of treatment in thalassemic children.
Background: To evaluate the growth hormone reserve and the growth hormone response to recombinant human growth hormone (GH) in prepubertal thalassemic children with growth retardation.
Methods: Twenty thalassemic patients with short stature and delayed bone age were studied. Patients were randomized into GH-treated (n=10) and non-GH treated (control; n=10) groups. The GH-treated group received recombinant human (rh)-GH (Genotropin) at the dose of 0.7 IU/kg per week for 12 months.
Results: There was a significant discordance between GH response to pharmacologic stimuli and physiological secretion of GH/GHRH testing. Following the administration of rhGH, growth velocity increased from 2.47~0.48 cm/year to 6.27~0.76 cm/year (P=0.005), whereas there was not a similar change in the non-GH-treated group. The height velocities of the two groups during the 1 year follow-up period were significantly different (6.27~0.76 vs 3.99~0.34 cm/year; P=0.025). There were significant differences between the height velocity improvements and height velocity standard deviation scores of the two groups as well.
Conclusion: The present study has demonstrated that rhGH is a safe and efficacious mode of treatment in thalassemic children.
Various growth parameters of 233 (140 boys, 93 girls) thalassemic children were compared with 74 (45 boys and 29 girls) non-thalassemic
siblings, ICMR and NCHS norms. Weight and height were retarded in thalassemic children. The difference between thalassemic
and nonthalassemic siblings, was evident from 9+ years in both boys and girls. Growth parameters seemed to be adversely affected
with the advancing age. Among head, chest and mid arm circumferences, the mid arm circumference was more affected than head
and chest circumferences. Height and weight were more severely retarded in children with hemoglobin levels of less than 8gm/dl.
The findings seemed to suggest that press of retardation was probably secondary to chronic hypoxia and iron overload.
In 12 patients affected by thalassemia major who received an intensive transfusion regimen combined with continuous iron chelation therapy (desferrioxamine 50–80 mg/kg daily), radiologic abnormalities of the long bones were observed similar to those observed in rickets and scurvy. These abnormalities were associated with a growth retardation. The pathogenesis of these lesions is uncertain, but probably the toxic effect of desferrioxamine plays an important role in their development. A relative deficiency of vitamins D and/or C cannot be entirely excluded.