Lulin Choubtum

Bone mineral density, biochemical and hormonal profiles in suboptimally treated children and adolescents with β‐thalassaemia disease

objective Thalassaemia/haemoglobinopathy is a hereditary disease causing increased erythropoiesis and expansion of the bone marrow cavity. As a consequence, there is a reduction in trabecular bone tissue resulting in osteopenia/osteoporosis. The present study was performed to assess bone mineral density (BMD) in children and adolescents with β‐thalassaemia disease and to determine biochemical and hormonal changes that may affect BMD.

Association between bone mineral density and erythropoiesis in Thai children and adolescents with thalassemia syndromes

Increased marrow erythropoiesis in patients with thalassemia syndromes results in the expansion of bone marrow cavities and consequently decreases bone tissues, leading to osteoporosis. Whether the soluble transferrin receptor (sTfR), a marker of erythropoietic activity, correlates with the bone mineral density (BMD) in thalassemic patients has not previously been addressed. Forty-six children and adolescents with thalassemia syndromes, who were either not transfused or suboptimally transfused, were studied. BMD was determined by dual-energy X-ray absorptiometry. Blood samples were obtained in order to determine sTfR and hemoglobin. The patients were categorized into four groups: 1, β-thalassemia/hemoglobin E (β-thal/E) with transfusion-dependency (TD) (n = 18); 2, β-thal/E with transfusion-independency (TI) (n = 15); 3, β-thalassemia major (β-major) (n = 6); 4, hemoglobin H (HbH) (n = 7). All patients had normal serum free thyroxine (FT4) and thyroid-stimulating hormone (TSH), and intact parathyroid hormone (PTH), serum calcium (Ca), phosphate (P), and 25-OH-vitamin D levels. The BMD of patients in the β-major and β-thal/E with TD groups were not significantly different. In comparison with the β-major and β-thal/E with TD groups, the β-thal/E with TI and HbH groups had significantly higher BMD of the total body (TB), femoral neck (FN), and lumbar spine (LS), as well as higher levels of hemoglobin. In contrast, the sTfR levels of the β-major, β-thal/E with TI, and HbH groups were significantly lower than those of the β-thal/E with TD group. The BMD of TB, FN, and LS was negatively correlated with the sTfR level, but positively correlated with the hemoglobin level. In conclusion, increased marrow erythropoiesis is one of the major determinants of reduced bone mass in thalassemic patients with either no transfusion or suboptimal transfusion.

Glucocerebrosidase mutations in Thai patients with Parkinson's disease

BACKGROUND GBA mutations are an important risk factor in developing Parkinsons disease (PD) worldwide. The study aimed to determine the frequency and clinical characteristics of GBA mutations in a Thai PD cohort of 480 patients and 395 control subjects. METHODS Direct sequencing of GBA was performed in all early-onset PD patients (EOPD: n = 108) and 100 PD patients with age at onset over 50 years (AAO > 50y-PD). The study subsequently screened all identified mutations in the remaining AAO > 50y-PD patients and all control subjects. Predictive factors associated with risk of developing PD were analyzed. Comparisons of clinical characteristics of PD patients with and without GBA mutations were also carried out. RESULTS Heterozygous GBA mutations were identified in 24 patients (5%) and 2 controls (0.5%). Seven identified GBA point mutations comprised p.L444P, p.N386K, p.P428S, IVS2+1G > A, IVS9+3G > C, IVS10-9_10GT > AG and c.1309delG, of which five mutations were novel. Multiple logistic regression analysis revealed that GBA mutations were more frequent in EOPD than AAO > 50y-PD groups (OR = 4.64, P < 0.022). Patients with GBA mutations had mean age at onset (43.1 ± 10.2, mean ± standard deviation) earlier than patients without GBA mutations (54.4 ± 13.9, P = 0.002). The patients with GBA mutations also had a more rapid progressive course, in which they were more likely to have higher Hoehn and Yahr staging (OR = 4.20, P = 0.006) and slightly lower means of Schwab-England ADL score [74.1 ± 17.1 vs. 81.0 ± 18.08 (OR = 0.98, 95%CI = 0.96-1.01, P = 0.162)]. CONCLUSION GBA mutations are an important risk of PD in the Thai population. Patients having the mutations are likely to have early onset and may exhibit more rapid motor progression.

Short-term cyproheptadine therapy in underweight children: effects on growth and serum insulin-like growth factor-I.

BACKGROUND Cyproheptadine, an appetite stimulant, has been used in poor-appetite underweight children. Its beneficial effects on enhancing growth rate have been demonstrated. In contrast, an adverse effect on blunting growth hormone (GH) secretion has also been reported. To date, however, its effect on insulinlike growth factor-I (IGF-I), a GH-mediated growth factor, has not been documented. AIM To examine the effect of cyproheptadine therapy on growth and serum IGF-I in underweight children. METHODS Twenty-one underweight, otherwise healthy children were recruited. They were randomly assigned into cyproheptadine administration (n = 10) and placebo (n = 11) groups. The former received cyproheptadine for 4 months. Serum IGF-I levels were measured in both groups. RESULTS Weight and height velocities and IGF-I z-scores during cyproheptadine therapy were significantly greater in the intervention group than those of the placebo group. CONCLUSION Cyproheptadine therapy in underweight children increased caloric intake and serum IGF-I concentration and consequently enhanced growth velocity.

Bone mineral density in children and young adults with beta-thalassemia trait.

BACKGROUND Homozygous beta-thalassemia is a hereditary hematological disease due to defective beta-globin synthesis. Consequently, there is ineffective erythropoiesis and increased peripheral hemolysis. Increased erythropoiesis in bone marrow results in expansion of marrow cavity and reduced bone mass. Patients with heterozygous beta-thalassemia or beta-thalassemia trait may have mild anemia, and consequently mildly increased erythropoiesis. Whether modestly increased erythropoiesis might decrease bone mass is not well established. OBJECTIVE To evaluate bone mineral density (BMD) in children and young adults with beta-thalassemia trait. METHODS Thirty-one healthy young adults aged 20-45 yr and 26 healthy children aged 8-15 yr with beta-thalassemia trait were enrolled in the study. BMD was determined by dual X-ray absorptiometry (DEXA). Determinations of intact parathormone (PTH), 25-hydroxyvitamin D (25-OHD), and bone markers were performed. RESULTS In adults, all had z-scores of BMD more than -2 above the mean. The mean z-scores of BMD of lumbar spine, radius and femoral neck were 0.11, -0.10 and 0.41, respectively. In children, only two of 26 had z-scores of lumbar spine BMD more than -2 below the mean. The mean z-scores of BMD of total body, lumbar spine, radius and femoral neck were 0.12, -0.28, 0.30 and -0.14, respectively. All subjects had normal PTH, 25-OHD and bone markers levels. CONCLUSION beta-Thalassemia trait is not a contributing factor for osteopenia/osteoporosis in children and young adults.

Four novel and three recurrent mutations of the BTK gene and pathogenic effects of putative splice mutations

AbstractX-linked agammaglobulinemia is caused by mutations in the human BTK gene, leading to recurrent pyogenic infections. We describe four novel and three known BTK-mutations in seven patients from seven (six Thai and one Burmese) families. All but one were sporadic cases. Patients 1 and 2 had recurrent mutations in exon 10 (R288W) and exon 17 (R562W), respectively. Patient 3, a previously healthy individual who presented with pseudomonas sepsis with ecthyma gangrenosum had a known mutation in exon 17 (1749delT), leading to frameshift effect (F583fsX586). Patient 4 manifested with sepsis and concurrent acute appendicitis and pneumonia. He had a mutation, IVS8 + 1G > A, which led to an insertion of intron 8 into the transcripts. In Patient 5, a novel change in exon 7, c.588G > C, initially presumed Q196H, was found to cause a leaky splicing mutation, resulting in three distinct transcripts containing 17, 108, and 190 bp of the 5′-terminal of intron 7, which led to truncated peptides consisting of 203 and 211 amino acid residues (or Q196fsX204 and Q196fsX212, respectively). Patient 6 had a mutation in exon 14 (W421X), while patient 7 had a newly defined large deletion of exons 6-9. All of the mothers tested were mutation carriers. Transcript analysis in three mothers who were heterozygous for frameshift mutations revealed a minimal amount of aberrant transcripts, while their affected children had full expression of the mutant alleles, suggesting rapid degradation due to nonsense-mediated mRNA decay in the mothers. This is the first report of mutations of BTK from Thailand.

Final Height after Long-Term Growth Hormone Treatment in Thai Children with Turner Syndrome

This article is also accessible online at: http://BioMedNet.com/karger We presented 12 Thai girls with Turner syndrome treated with recombinant human growth hormone (rhGH) in an effort to augment the rate of growth and improve final height. The girls ranged in age from 6.1 to 14.8 years. The range of their bone ages was from 4.1 to 10 years. All were prepubertal at the time of study. The standard deviations (SD) in their heights and weights, as based upon normal Thai standards, were –3.72 B 1.88 and –1.39 B 2.89 (mean B SD) respectively. The mean pretreatment height velocity (HV) was 2.83 B 0.56 (mean B SD) cm/year (table 1). The girls were treated for a period of 1–5 years with rhGH. The dosage of 0.1–0.125 IU/kg/day was administered by daily subcutaneous injection. The mean HV increased significantly over the treatment period, to 8.78 B 1.49 cm/year in the first year of treatment, 6.57 B 1.69 cm/year in the second year, and 5.38 B 2.03 cm/year in the third year. In addition, the mean height SDS and weight SDS increased to –2.59 B 1.54 and –0.88 B 2.50 respectively. Six patients reached final adult height. This final height ranged from 136.8 to 147.9 cm with mean B SD of 142.4 B 5.03 cm which is significantly improved in comparison with 136.2 B 1.47 cm in that of untreated Turner syndrome in the Thai population. All patients had normal glycosylated hemoglobin and normal thyroid function tests before and during treatTable 1. Chromosome karyotypes

Trinucleotide repeat expansion of TATA-binding protein gene associated with Parkinson's disease: A Thai multicenter study

INTRODUCTION Spinocerebellar ataxia type 17 (SCA17) is an inherited cerebellar degeneration associated with trinucleotide repeat expansions in the TATA-binding protein gene (TBP). Low-range expansions of TBP have recently been described in association with Parkinsons disease (PD). However, these low-range expansion alleles were also observed in healthy individuals. Prior distinct findings may result from reduced penetrance or age-dependent susceptibility, which may influence phenotypic expression. METHODS A case-control study of 456 PD patients and 374 control subjects was conducted. Data and blood samples were collected during 2008-2013. Control subjects were individuals over 65 years old without parkinsonism. Sizes of TBP trinucleotide repeats were analyzed. All available carriers of the TBP repeat of ≥40 repeats were re-examined. RESULTS A high prevalence of carriers of TBP repeat expansion ≥41 developed PD, mainly at an advanced age. Half of these carriers had onset after 70 years of age (range 34-84). Seven participants carried expansion alleles of ≥42, and all had PD. Fourteen participants (six patients and eight controls) carried a heterozygous 41-repeat allele. At the current mean age of 79 years and mean follow-up period of 4 years, three out of the eight control carriers of the 41-repeat allele developed PD, while none of the thirteen asymptomatic carriers of the 40-repeat allele did. CONCLUSIONS A high prevalence of PD was observed in carriers of low-range expansions of TBP (41-45 repeats), especially in elderly. This finding suggests that cut-off value for pathological TBP repeat expansion appear to be 41.

Skewed X Chromosome Inactivation in Girls and Female Adolescents with Autoimmune Thyroid Disease.

Skewed X chromosome inactivation (XCI) was associated with female predominance in adult autoimmune thyroid disease (ATD). In normal females, skewed XCI is increased with age. Whether early‐onset skewed XCI is associated with childhood ATD remains unknown. This study aimed to determine XCI skewing in paediatric ATD.