Chronic Hemolysis May Adversely Affect Skeletal Health. A Cross-Sectional Study of a Pediatric Population.

Hereditary hemolytic disorders cause ineffective erythropoiesis and bone marrow hyperplasia. Little is known about their effect on growth and skeletal health. The aim of this study was to evaluate growth, bone and body composition of non transfusion-dependent (NTD) pediatric patients with chronic hemolysis. A detailed history and clinical examination, dual-energy X-ray absorptiometry (DXA) of the lumbar spine (LS) and total body less head (TBLH) and bone turnover markers were performed. Thirty-nine patients (22 males and 17 females, 20 prepubertal), aged 11.4 ± 3.6 years [14 had ß-thalassemia intermedia (ß-TI), 17 α-thalassemia (α-thal) and eight hereditary spherocytosis (HS)] were evaluated. Fifty-seven previously studied controls were used for statistical analysis. The patients had lower weight and body mass index (BMI) (Z-scores -0.2 and -0.3, respectively, p < 0.05). Post-traumatic fractures were reported by 28.0% of the patients. Compared to controls, they had lower lumbar and subcranial bone mineral density (BMD), as well as reduced fat mass (FM), whereas muscle mass was not affected. One in three patients had low vitamin D and there was increased bone resorption and reduced bone formation. Correlations between different parameters revealed a potential role of osteocalcin, hemoglobin (Hb) and lactate dehydrogenase (LDH) as prognostic markers for bone health, in the setting of chronic hemolysis. Hereditary spherocytosis (HS) patients were the least affected in terms of growth and bone profile. Chronic hemolysis may lead to impaired growth and bone health, even in young, NTD patients. The degree of hemolysis determines bone health risk. Regular surveillance of bone health is justifiable.

The effect of PKU diet on the maternal quality of life and social discrimination in relation to their educational status and place of living.

Background Phenylketonuria (PKU) is an inherited metabolic disorder characterized by high levels of phenylalanine in the blood and brain, resulting in mental retardation, etc. Dietary treatment with low phenylalanine is the common treatment for this disease. Patients with other metabolic disorders, such as diabetes mellitus, were reported to have a higher percentage of quality-of-life damage (QLD) and social discriminations (SDs). Methods To evaluate the degree (%) of maternal QLD and SD in relation to their educational status and place of living during the participation of their PKU children in public events, 110 mothers of PKU children with an average age of 25.7 years took part in this study. We evaluated their QLD and SD according to their educational status (primary school, high school and university) and place of living (small town ≤300,000, city >300,000 inhabitants). A control group was not needed. Special questions (checklist) were created to evaluate the QLD and SD of the mothers of children under dietary control. Cronbach's α test was used for the measurement of the function of the items in the checklists. Results The covariance between the item pairs and the variance of the total score were calculated. Mothers who had completed primary school and lived in a city with a population >300,000 experienced the highest degree of QLD. In contrast, mothers with a university degree experienced the lowest SD. Overall, the highest SD was observed in mothers who lived in a small town. The affected group of mothers should be psychologically supported.

Body composition of patients with Duchenne muscular dystrophy: the Greek experience.

Greece ranks among the first countries suffering from the obesity epidemic globally. The aim of the study was to evaluate body composition in Greek patients with Duchenne muscular dystrophy (DMD). We hypothesized that able-bodied patients would not differ from controls, in terms of adiposity, based on clinical observations during everyday practice. STUDY DESIGN: Cross-sectional study of steroid-dependent DMD subjects, who underwent dual-energy X-ray absorptiometry and laboratory metabolic bone profile evaluation. Forty-two patients and thirty-one controls were studied. Overall, DMD subjects were shorter (height Z-score = -1.4, p = 0.01). Their bone mineral density (BMD) was low (lumbar spine BMD Z-score = -1.2, p < 0.01, subcranial total body BMD Z-score = -1.8, p < 0.01). Lean tissue mass (LTM) was also decreased (LTM Z-score = -2.2, p < 0.01). The above findings were more pronounced in adolescence. Regarding adiposity, increased fat mass (FM) was found only in pubertal DMD patients (FM Z-score = 1.4, p < 0.01), whereas prepubertal, able-bodied patients did not differ from controls, thus confirming the initial hypothesis. Finally, 65 % of DMD subjects had increased bone resorption markers and 57 % had suboptimal vitamin D levels. The importance of using native population as controls for body composition analysis is highlighted. In Greece, abnormal body composition in DMD patients is more striking when loss of ambulation occurs and not during the prepubertal period, due to the concurrent presence of obesity in the pediatric population. Thus, adolescents with this neuromuscular disorder should be targeted toward prompt lifestyle interventions.

α-Synuclein dimerization in erythrocytes of Gaucher disease patients: correlation with lipid abnormalities and oxidative stress.

Several observations suggest that disturbed homeostasis of α-Synuclein (α-Syn) may provide a link between Gaucher disease (GD) and Parkinson's disease (PD). We recently reported increased dimerization of α-Syn in the red blood cell (RBC) membrane of patients with GD. Several studies indicate a crucial relationship between lipids, oxidative stress and α-Syn status. Here we investigated the relationship between the observed increased dimerization of α-Syn in the cell membranes of RBCs, cells devoid of lysosomes and lacking lysosomal enzyme synthesis, and the lipid abnormalities and oxidative stress already described in GD. Correlation studies showed that in GD the α-Syn dimer/monomer ratio is positively correlated with the levels of glucosylceramide (GlcCer) and the glucosylceramide/ceramide (GlcCer/Cer) ratio and negatively with the levels of malonyldialdehyde (MDA) and plasmalogens. In conclusion, we have shown that the increased tendency of α-Syn to form dimers in the RBC membrane of patients with GD, is correlated with both the level of lipids, including GlcCer, the primary lipid abnormality in GD, and the increased oxidative stress observed in this disorder. The study of other tissues, and in particular brain, will be important in order to elucidate the significance of these findings regarding the link between GD and PD.

Body composition profile of young patients with phenylketonuria and mild hyperphenylalaninemia.

BACKGROUND: There is evidence in support of low bone density in young patients with disorders of phenylalanine metabolism; however, little is known about muscle and fat mass in these patients, especially in those with mild hyperphenylalaninemia (mHPA). OBJECTIVES: We aimed to evaluate body composition of children and adolescents with early-diagnosed disorders of phenylalanine metabolism. PATIENTS AND METHODS: The study was conducted in the Institute of Child Health, which is the national center that performs newborn screening. Bone, muscle, and fat mass of 48 patients with phenylketonuria (PKU) and 32 patients with mild mHPA, aged five to 18 years, were compared to 57 age- and sex-matched controls. Dual energy X-ray absorptiometry was used for this purpose. RESULTS: Compared to controls, bone mineral density (BMD) was lower in patients with PKU (mean total body BMD z score, 0.11; P = 0.03) and in those with mild mHPA (mean lumbar BMD z score, -0.34; P = 0.01). Lean body mass and fat mass were not significantly affected in the study group. Comparison between the two patients groups did not reveal any difference in body composition profiles; however, pubertal status appeared important for within-group comparisons. Fat mass was significantly increased in teenagers with PKU, which was more evident in those with poor dietary compliance irrespective of gender (fat mass z score, 0.66; P = 0.018). Finally, positive correlations were found not only between bone, muscle, and fat mass in both groups, but also between fat mass and Phenylalanine levels in patients with PKU (r, 0.46; P = 0.001). CONCLUSIONS: Bone mineral density appears suboptimal in young patients with disorders of phenylalanine metabolism. Adolescents seemed more prone to obesity, especially when their dietary adherence was poor, whereas muscle mass was not considerably affected. To ensure healthier bones and less fat content, close follow-up as well as proper lifestyle advice is needed.

Gaucher disease: plasmalogen levels in relation to primary lipid abnormalities and oxidative stress.

Plasmalogens represent a unique class of phospholipids. Reduced red blood cell plasmalogen levels in Gaucher disease patients were reported, correlating to total disease burden. The relation between plasmalogen abnormalities in Gaucher disease patients and primary glycosphingolipid abnormalities, malonyldialdehyde levels, an indicator of lipid peroxidation, and the total antioxidant status was further investigated. Significant reduction of C16:0 and C18:0 plasmalogens in red blood cells of Gaucher disease patients was confirmed. In parallel, a significant increase in the glucosylceramide/ceramide ratio in red blood cell membranes, as well as an average 200-fold increase in plasma glucosylsphingosine levels was observed. Red blood cell malonyldialdehyde levels were significantly increased in patients, whereas their total antioxidant status was significantly reduced. A negative correlation between plasmalogen species and glucosylceramide, ceramide, glucosylceramide/ceramide ratio, glucosylsphingosine and malonyldialdehyde, significant for the C16:0 species and all the above parameters with the exception of malonyldialdehyde levels, was found along with a positive non-significant correlation with the total antioxidant status. Our results indicate that increased lipid peroxidation and reduced total antioxidant status exist in Gaucher disease patients. They demonstrate a clear link between plasmalogen levels and the primary glycolipid abnormalities characterizing the disorder and an association with the increased oxidative stress observed in Gaucher disease patients.

Body composition in young patients with galactose metabolic disorders: a preliminary report.

AIM: Body composition evaluation in patients with galactosemia and its variants. METHODS: The body composition of young subjects with galactose metabolic disorders was analyzed with dual X-ray absorptiometry. The subjects were divided into the classic galactosemia (CG; n=14) group and the group with other galactose metabolic disorders (OGMD, e.g., epimerase deficiency; n=8). RESULTS: In both groups, bone strength and bone mineral density Z-scores were normal. However, CG patients appeared sarcopenic (median muscle mass Z-score=-1.93), whereas OGMD subjects had low-normal muscle mass. In addition, approximately half of all patients were overweight. In CG patients, bone mass was strongly correlated to muscle mass (r=0.81), whereas in OGMD patients it was positively correlated to body mass index (r=0.78). CONCLUSIONS: An imbalance between muscle and fat mass, especially in patients with classic galactosemia, was observed. Given the observed strong correlation between bone and muscle mass, more effective lifestyle counseling is needed.

Bone health evaluation of children and adolescents with homozygous ß-thalassemia: implications for practice.

OBJECTIVE: Bone tissue is adversely affected in patients with homozygous ß-thalassemia. The aim of this study was to find warning signs of bone loss in young patients with ß-thalassemia and allow prompt therapeutic interventions. METHODS: Thirty-eight patients were studied, 20 boys and 18 girls, aged 5 to 18 years (median = 14.13 y), on regular transfusions and chelation treatments. Their bone mineral density (BMD) was measured with dual x-ray absorptiometry. The recorded parameters were weight, height, bone age (BA), transfusion adequacy (mean fetal hemoglobin value), and chelation efficacy (mean ferritin value, compliance). Tanner stage was also evaluated: 8 prepubertal subjects (stage 1), 18 peripubertal subjects (stages 2 and 3), and 12 postpubertal patients (stages 4 and 5). Blood and urine samples were collected for biochemical analysis. RESULTS: Mean BMD z score was -1.56 ± 1.25. Thirteen patients had normal BMD (z score >-1), 17 patients had low BMD (z score: -1 up to -2.4), and 8 patients had very low BMD (z score <-2.5). Low BMD was observed in patients older than 12 years and was associated with short stature (r = 0.33, P = 0.04), delayed BA (r = 0.61, P = 0.01), and increased bone formation markers. There was no correlation of BMD z score with sex, fetal hemoglobin value, ferritin, and compliance. Regarding Tanner stage, it was associated strongly with short stature (r = 0.57, P = 0.01), ferritin (r = -0.38, P = 0.02), and compliance (r = 0.58, P = 0.01). CONCLUSIONS: [corrected] The decline in BMD may start early, even in the well-transfused patients. This study targets the young patients who are mostly at the risk for bone loss, that is short adolescents with delayed BA. Their prompt recognition in everyday practice is important, as they will need close monitoring of their BMD and metabolic bone profile. In addition, therapeutic interventions, such as adequate calcium intake and sunlight exposure, weight-bearing exercise and, in cases of vitamin D insufficiency, proper supplementation could be suggested.

ß-Glucocerebrosidase gene mutations in two cohorts of Greek patients with sporadic Parkinson's disease.

An increasing number of clinical, neuropathological and experimental evidence linking Gaucher disease and a spectrum of synucleinopathies, including Parkinson's disease (PD) has emerged over the last decade. In particular, several studies, despite individual differences, have shown that mutations in the ß-glucocerebrosidase gene (GBA) are a risk factor for PD. Recently a study from Northern Greece has shown a significant overrepresentation of such mutations only in patients with early onset PD. In the present study 8 different GBA mutations covering 87% of the mutations identified in Gaucher disease patients diagnosed in Greece were investigated in two ethnic Greek cohorts of patients with sporadic Parkinson's disease. Cohort A included patients residing and originating from Thessaly, Central Greece (n=100) and cohort B included patients residing and/or originating from the greater area of Athens (n=105). Age-gender-ethnicity matched healthy individuals from the same areas were included as controls (n=206). In patients of cohort A 11 carriers of GBA mutations were identified (5/11:N370S, 2/11:L444P, 2/11: D409H;H255Q, 1/11:H255Q, 1/11D409H) as opposed to 3 in the controls (n=105) (1/3:N370S, 1/3:H255Q, 1/3:Y108C) (p=0.021, OR 4.2, 95% CI=1.14-15.54). In patients of cohort B 10 carriers of GBA mutations were identified (4/10:L444P, 4/10:D409H;H255Q, 1/10:N370S, 1/10:IVS10-1G→A) as opposed to 4 in controls (n=101) (3/4:N370S, 1/4:L444P). However the difference was not statistically significant (p=0.113, OR 2.5, 95% CI=0.77-8.42). In both cohorts, patients with PD harboring a GBA mutation had an earlier onset of symptoms than non-carriers (p=0.034, p=0.004). The overall difference in the number of carriers identified in PD patients and controls was statistically significant (p=0.006; OR 3.24; 95% CI=1.35-7.81). The association was reinforced in the early onset PD patients (EOPD; n=28, p=0.000, OR 11.37; 95% CI=3.73-34.6). In conclusion GBA mutations were identified with increased frequency in both geographical cohorts of patients with sporadic PD studied compared to control individuals, with the difference being statistically significant only in cohort A. An impressive association with EOPD was found and one third of the EOPD patients examined harbored a GBA mutation. Qualitative differences regarding the type of mutations and/or their relative frequencies were observed between cohorts A and B of PD patients. Genetic and/or environmental factors may account for the observed differences.