Growth and development in thalassaemia major patients with severe bone lesions due to desferrioxamine

Nine transfusion-dependent -thalassaemia major patients (seven males and two females), aged 4–15 years, with growth retardation and severe rickets-like radiological lesions due to continuous subcutaneous chelation therapy with desferrioxamine (45–75 mg/kg body weight, 6–7 times/week), were seen in our centre during the last 8 years. Serum ferritin levels ranged from 976 to 4115 g/l. There was a progressive decline in growth velocity in these patients 2–3 years before the appearance of rickets-like radiological lesions. All patients underwent surgery to correct genu valgum and/or slipped capital epiphyses. The final height was below the 3rd percentile in six patients (SDS: from –2.9 to –5.2). The short stature was mainly due to a disproportion between upper and lower segments. Six of the patients had an associated sensorineural hearing loss.Conclusion Our data emphasize the importance of an accurate surveillance of the toxic effects of desferrioxamine treatment and warn of the risk of overtreating patients with low iron overload and also suggest a possible individual idiosyncrasy to the adverse effects of chelation therapy.     

Non-coronary cardiac events,younger age,and IVIG unresponsiveness increase the risk for coronary aneurysms in Italian children with Kawasaki disease

Clinical Rheumatology - Kawasaki disease (KD) is the most frequent cause of acquired heart disease in children in high-income countries because of coronary artery involvement. Risk factors for...     

Effectiveness of partial splenic embolization as treatment for hypersplenism in thalassaemia major: a 7-year follow up.

Partial splenic embolization is an alternative procedure to total splenectomy in patients with hypersplenism, and was performed in 10 patients with beta-thalassaemia major who were then followed for 5 to 7 years. The results were compared with those of a 7-yr follow-up of 6 splenectomized thalassaemics. The blood consumption decreased and the leucocyte counts increased in both groups of patients. However, after partial splenic embolization, severe thrombocytosis--which is typical of splenectomized patients--did not develop and there were no severe complications from the operation, such as infections or reappearance of hypersplenism. In addition, the minor surgical injury and avoidance of abdominal scars were further advantages of partial splenic embolization over total splenectomy.     

Growth hormone secretion and bone histomorphometric study in thalassaemic patients with acquired skeletal dysplasia secondary to desferrioxamine

An auxological and endocrinological study was performed in 21 thalassaemic patients with growth retardation and skeletal dysplasia secondary to desferrioxamine. Bone metaphyseal proximal tibial or iliac crest biopsy was performed in six patients with severe genu valgum or non-traumatic vertebral compression. GH insufficiency/deficiency (GH deficiency: peak after stimulation test below 6 ng/ml) was found in 72% of our thalassaemic patients with skeletal dysplasia, but in only 41% of patients without skeletal dysplasia. Bone histology showed abnormal chondrocytes, alteration of staining pattern of cartilage, irregular columnar cartilage and lacunae in the cartilaginous tissue. The behaviour of bone tissue was unpredictable (presence of thick or thin osteoid layer). Bone microfractures were sometimes present. The bone microstructure showed scarce mineralization, which was evenly or irregularly distributed. The bone tissue apatitic phase was quantitatively reduced. The hardness of bone tissue was remarkably lower than that of normal bone in three out of six patients. In conclusion, iron chelation therapy in patients with acquired skeletal dysplasia seems to interfere with GH secretion. The early identification of clinical and radiological abnormalities of skeletal dysplasia is of paramount importance in preventing severe bone destruction.     

Epidemiology of rotavirus-associated hospital admissions in the province of Ferrara, Italy

Overview

Hospital discharge forms with specific codes for rotavirus gastroenteritis in children 0 to 14 years of age were reviewed in the period 2003–2005 in the province of Ferrara.

Results

A total of 4,238 children were admitted to the pediatric departments; 151 patients were diagnosed with rotavirus gastroenteritis. The average annual rate of hospitalization for rotavirus gastroenteritis was 1.54/1,000 children <14 years of age and 2.9/1,000 children <5 years of age. Most hospitalizations (72%) involved children aged <60 months. The average length of hospital stay was about 5 days. Considering the Emilia Romagna regional reimbursement codes referable to rotavirus disease, the estimated costs of our 151 cases range from €214,033 to €341,832.

Conclusions

The results of this study contribute to the awareness of rotavirus epidemiology in Italy and underline the potential impact of rotavirus vaccination in our province.     

Papillary thyroid cancer in thalassaemia

Thyroid cancer is the most frequent endocrine neoplasm in the general population. Its incidence is 5-10/100,000 per year, with an annual death rate of 0.2-1.2/100,000 in men and 0.4-2.8/100,000 in women. In thalassaemia patients the frequency of this disease is unknown. In this paper we describe five cases of papillary thyroid cancer in thalassaemia patients followed at the Day Hospital for Thalassaemia and Haemoglobinopathies, in Ferrara, Italy. We consider the possible key role of iron as a carcinogenic agent and we also discuss the practical implications of our clinical observations.     

Identification of fifteen novel mutations in the SLC12A3 gene encoding the Na-Cl Co-transporter in Italian patients with Gitelman syndrome

The SLC12A3 gene encodes the thiazide-sensitive Na-Cl co-transporter (NCCT) expressed in the apical membrane of the distal convoluted tubule of the kidney. Inactivating mutations of this gene are responsible for Gitelman syndrome (GS), a disorder inherited as an autosomal recessive trait. We searched for SLC12A3 gene mutations in 21 Italian patients with the clinical and biochemical features of GS (hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria, and the absence of nephrocalcinosis). All coding regions with their intron-exon boundaries were analyzed using PCR and SSCP techniques followed by sequencing analysis. We identified 21 different mutations evenly distributed throughout the gene without any mutation hot-spot. Fifteen are novel variants, including 12 missense mutations, one deletion, one deletion-insertion and one splice site mutation: R158Q, T163M, W172R, G316V, G374V, G463E, A464T, S615W, V677M, R852S, R958G, C985Y, 2114-2120delACCAAGT, 2144-2158delGCCTTCTACTCGGATinsTG, and 531-2A>G.     

Osteochondrodystrophic Lesions in Chelated Thalassemic Patients: An Histological Analysis

Some patients affected by thalassemia major and treated with an iron-chelating drug such as deferioxamine can suffer from severe osteochondrodystrophic lesions of the long bones. These lesions were radiologically and clinically evident in 2.8% of the patients we examined over the last 10 years. The aim of our research was to evaluate the morphology and morphometry of five tibial biopsy specimens taken from thalassemic patients with bone lesions and two bone biopsy specimens taken from thalassemic patients with no alteration of the long bones. All the bone samples showed a similar morphostructure. Abnormal chondrocytes, alteration of cartilage staining pattern, irregular columnar cartilage, and lacunae in the cartilaginous tissue were revealed histologically. Osteoid thickness was either normal or slightly increased. Some bone trabeculae had microfractures and some had cartilagineous oases. In five cases, iron deposition was detectable by Perls' Prussian Blue staining. It can be concluded that even in patients without radiographic signs of lesions, seriously damaged columnar cartilage, altered bone mineralization, and microfractures are common. Received: 28 June 1999 / Accepted: 8 March 2000