Comparative study of dual energy X-ray absorptiometry and quantitative ultrasonography with the use of biochemical markers of bone turnover in boys with haemophilia.

Our aim was to evaluate bone status in boys with haemophilia using dual energy X-ray absorptiometry (DXA) and quantitative ultraSonography (QUS), and in addition, to compare these two methods with the use of biochemical markers of bone turnover. Twenty-six boys with a mean decimal age of 12.08 ± 4.44 years were included in the study which included a DXA scan at lumbar spine and radial, as well as tibial QUS. Serum levels of soluble receptor activator of nuclear factor κB ligand (sRANK-L), osteoprotegerin (OPG) and osteocalcin (OC) were measured and joint evaluation was performed using the Hemophilia Joint Health Score (HJHS). With regard to the study results, only 2 of 26 patients (7.7%) had bone mineral density (BMD) Z-scores < -2, and 4 patients (15.4%) had BMD Z-scores between -1 and -2. Only one patient had radial and other two had tibial QUS Z-scores < -2. No agreement was recorded between QUS and DXA in identifying patients at risk for osteoporosis (k = 0.275, P = 0.063). Haemophiliacs had significantly higher serum levels of sRANK-L (21.04 ± 4.78 vs. 18.58 ± 2.28 ng mL(-1), P = 0.038) and of OC (5.35 ± 2.29 vs. 3.09 ± 0.61 ng mL(-1), P = 0.002) and significantly decreased levels of OPG (15.78 ± 2.53 vs. 23.79 ± 4.39 pg mL(-1), P < 0.001) compared with controls. QUS Z-scores at tibia significantly correlated with HJH Scores (r = -0.450, P = 0.040), whereas lumbar BMD Z-scores significantly correlated with body mass index Z-scores (r = 0.500, P = 0.009). More studies are warranted to identify the most accurate densitometric method for assessing bone status in haemophiliacs.

A patient with Klinefelter's syndrome and thalassemia intermedia.

Klinefelter's syndrome (KS) is associated with a wide spectrum of clinical features, such as tall stature, eunuchoid proportions, testes disproportionately small for the level of pubertal development, gynecomastia and behavioral problems. The association of KS with thalassemia intermedia has not been previously reported. A male patient with thalassemia intermedia was diagnosed with KS at the age of 14 years when endocrine evaluation for delayed puberty showed hypergonadotrophic hypogonadism. Thyroid function was normal; however, basal and GnRH-stimulated gonadotropin concentrations were raised while serum testosterone was low. Karyotype analysis revealed KS (47,XXY). Testosterone replacement therapy started soon after diagnosis and now at the age of 20 years the patient's height is 178.3 cm, the U/L ratio is 0.91. Testicular volume is 12 ml (Prader orchidometer) and his pubic hair is stage 4. To our knowledge this is the first case of a patient suffering from KS and thalassemia intermedia reported in the literature.

Hearing loss in children with sickle cell disease.

Hearing loss in children with sickle cell disease. Sickle cell anemia (S/S) has been associated with a high incidence of hearing loss mostly of the sensorineural type (SNHL). Twenty-four patients with sickle cell disease (13 female and 11 male; 22 patients belonging to the S/beta(+)-Thal and 2 to the S/S phenotype) with a mean age of 12.5 +/- 3.6 years and hemoglobin (Hb) levels range 6.5-11 g/dl underwent ENT examination, pure tone audiometry, speech audiometry, tympanometry, auditory reflex evaluation, tone decay test and brain auditory evoked potentials (BAEP) in order to evaluate the presence, type and degree of hearing loss. Only one patient (4.6%) who also sustained an infarct of the middle cerebral artery, demonstrated a unilateral SNHL in high tone frequencies exceeding 70 dB, as well as a prolonged III-V interpeak latency at the same side. No abnormalities were detected in the control group. These findings suggest a low incidence of SNHL in Greek SCD patients probably due to different hematological and clinical profile (S/beta(+)-Thal).

Urine biochemical markers of early renal dysfunction are associated with iron overload in beta-thalassaemia.

Renal dysfunction in thalassemia patients can be attributed to chronic anemia, and iron overload as well as to desferioxamine (DFO) toxicity. We analyzed the urine of 91 well-maintained homozygous beta-thalassemia patients, with no evidence of renal disease, for early evidence of kidney dysfunction by means of electrophoresis and quantitative biochemical tests. Measurement of liver magnetic resonance imaging (MRI) T2 values and serum ferritin concentration was used to estimate iron overload. In 55 of the 91 patients, urine analysis indicated signs of tubular dysfunction. The urine concentration of albumin and beta 2-microglobulin, as well as the activity of N-acetyl-beta-D-glucosaminidase (NAG), correlated positively with serum ferritin concentration and liver iron deposition, as detected by MRI T2 values. This suggested that the cause of renal dysfunction in homozygous beta-thalassemia is iron overload. On the other hand, the same urine markers did not correlate with age, indicating that chronic anemia or desferrioxamine (DFO) treatment are not related to renal dysfunction in thalassemia.

Long term audiological evaluation of beta-thalassemic patients.

OBJECTIVE: The objective of this study was to identify the incidence and to monitor the progression of hearing loss in children and young adults with beta-thalassemia major. METHODS: One hundred and four (104) patients aged 6-35 years (mean 17,2 years) participated in the study. All patients were on a regular transfusion-chelation program maintaining a mean hemoglobin level of 9.5 gr/dl. Subjects were receiving desferrioxamine (DFO) chelation treatment with a mean daily dose of 50-60 mg/kg, 5-6 days a week during the first six years of the study, which was then reduced to 40-50 mg/kg for the following eight years. Patients were followed for 8-14 years. RESULTS: Overall, 21 out of 104 patients (20.2%) presented with high frequency sensorineural hearing loss (SNHL), either unilateral or bilateral. No ototoxic factor, other than DFO, was present in any of the patients. Patients with SNHL presented with relatively lower serum ferritin levels than those with normal hearing, however, no statistically significant difference was observed. Subjects with SNHL were submitted to DFO reduction or temporary withdrawal. Following intervention, 7 out of 21 affected patients recovered, 10 remained stable and 4 demonstrated aggravation. CONCLUSION: The findings are indicative of DFO's contributing role in the development of hearing impairment. Regular audiologic evaluation is imperative in all thalassemic patients so that early changes may be recognized and treatment may be judiciously adjusted in order to prevent or reverse hearing impairment.