Prapai Dejkhamron

Enamel-renal-gingival syndrome and FAM20A mutations

The enamel‐renal syndrome of amelogenesis imperfecta (AI) and nephrocalcinosis, and the amelogenesis imperfecta‐gingival fibromatosis syndrome have both been associated with mutations in FAM20A. We report on two unrelated Thai patients with three novel and one previously reported mutations in FAM20A with findings suggesting both disorders, including hypoplastic AI, gingival fibromatosis, unerupted teeth, aggressive periodontitis, and nephrocalcinosis/nephrolithiasis. Additional findings consisted of a supernumerary premolar, localized aggressive periodontitis, thin alveolar bone, vitamin D deficiency‐associated hyperparathyroidism, and heterotopic calcification in other tissues, including lungs, dental pulp, gingiva, dental follicles, and periodontal tissues, and early cessation of limited menstruation. Greater promotory activity of urine on calcium oxalate crystal growth compared to controls may help to explain the pathogenesis, and suggest that FAM20A mutations can contribute to nephrocalcinosis/nephrolithiasis. Our findings expand the phenotypic spectrum of FAM20A mutations. Since both of our patients and a large number of previously reported cases had all the important features of both syndromes, including AI, renal anomalies, and gingival fibromatosis, we are convinced that these two disorders actually are the same entity. The name of enamel‐renal‐gingival syndrome is suggested.

Insulin resistance and lipid profiles in HIV- infected Thai children receiving lopinavir/ ritonavir-based highly active antiretroviral therapy

Abstract Background: Lopinavir/ritonavir (LPV/r) is associated with insulin resistance (IR). We aim to determine the prevalence of IR, dyslipidemia and their inter-relationships with adipokines in HIV-infected children treated with LPV/r-based highly active antiretroviral therapy (HAART). Methods: Twenty-eight children were enrolled. Fasting glucose, insulin, lipid profiles, adipokines, and oral glucose tolerance tests were performed. Results: The prevalence of IR, pre-diabetes mellitus, and hypertriglyceridemia was 42.9(12/28), 10.7(3/28), and 75.0(21/28)% respectively. No case met the definition for diabetes mellitus (DM) and lipodystrophy. Children with IR had higher BMI z-score, triglyceride levels but unchanged leptin or adiponectin levels compared to those without IR. Longer duration of LPV/r-based HAART was associated with increased levels of triglyceride and total cholesterol. Conclusions: We describe high prevalence of IR, pre-diabetes mellitus, and dyslipidemia among HIV-infected children receiving LPV/r-based HAART. Pre-diabetes mellitus or DM or IR screening might be important for early diagnosis and intervention in these children.

Radioactive Iodine for Thyrotoxicosis in Childhood and Adolescence: Treatment and Outcomes

Objective: The aim of the present study was to evaluate the outcome of radioiodine treatment in thyrotoxicosis in childhood and adolescence. Methods: This was a retrospective study of 27 patients (ages 7.2- 19.8 years) with a diagnosis of thyrotoxicosis who received iodine-131 (I-131) treatment from January 2007 to December 2011 in the Nuclear Medicine Division, Department of Radiology, Faculty of Medicine, Chiang Mai University. Gender, duration of antithyroid drug (ATD) treatment, 24-hour I-131 uptake, thyroid weight, total dose and number of treatments with I-131, and thyroid status at 6 months after treatment were recorded. Results: The outcomes of 27 patients (85.2% female, 14.8% male) treated with radioactive iodine were analyzed to assess the effectiveness of therapy as related to dose and gland size. All children and adolescents received 150 µCi of I-131/g of thyroid tissue (n=27). Six 6 months after treatment, 44.5% of the patients were hyperthyroid, 14.8% were euthyroid, and 40.7% were hypothyroid. Of the 12 cases with hyperthyroidism, 2 cases needed a second dose of I-131 treatment, and they finally reached a hypothyroid state. The patients were classified into 2 groups according to treatment success (euthyroid and hypothyroid) and treatment failure (hyperthyroid). There were no significant differences in age, gender, duration of ATD treatment, 2- and 24-hour I-131 uptake, thyroid weight, and total I-131 dose between these two groups. Conclusions: Radioiodine treatment is safe and effective for thyrotoxicosis in childhood and adolescence. It is suitable as a good second-line therapy for patients with severe complications, those who show poor compliance, and those who fail to respond to ATD treatment. . Conflict of interest:None declared.

Isolated methylmalonic acidemia with unusual presentation mimicking diabetic ketoacidosis.

Abstract Background: Hyperglycemic ketoacidosis is an acute, life threatening condition requiring early etiologic recognition and management to prevent serious morbidity/mortality. The most common cause is diabetic ketoacidosis (DKA). Organic acidemias (OAs) are inheritable disorders caused by defects in protein metabolism resulting in acid accumulation. Patients with metabolic decompensation usually present with acidosis, with/without hypoglycemia. Hyperglycemia is a very rare manifestation. At least 16 cases of OAs presenting with hyperglycemia have been reported. Six of the 16 were diagnosed with isolated methylmalonic academia (MMA) and three of the six passed away from late diagnosis. Case description: We describe a 2-year-old Thai girl who presented with hyperglycemia, acidosis and ketosis. She has underlying delayed development, seizures, optic atrophy and poor growth. An initial diagnosis of DKA was made and standard treatment was started. After 4 h of treatment, the patient partially responded to treatment; blood sugar decreased but acidosis and ketonemia persisted. HbA1c was normal. Investigations to rule out OAs were performed. Markedly elevated urinary methylmalonic acid consistent with MMA was observed. Molecular and enzyme analyses confirmed the diagnosis with isolated MMA. Specific treatment for MMA including protein restriction, high caloric fluid, carnitine and vitamin B12 was promptly started. Clinical improvement was seen 4 days after initiating specific treatment. Conclusions: Inherited metabolic disorders should be included in differential diagnosis in hyperglycemia ketoacidosis patients who respond poorly to standard DKA treatment. Unusual findings, e.g. hyperammonemia, lactic acidosis, pancytopenia, abnormal basal ganglia in MRI or underlying delayed development may indicate underlying OAs. Determining the etiology of hyperglycemic ketoacidosis is important and can lead to good outcomes.

Osteogenesis imperfecta with ectopic mineralizations in dentin and cementum and a COL1A2 mutation

We report a Thai father (patient 1) and his daughter (patient 2) affected with osteogenesis imperfecta type IV and dentinogenesis imperfecta. Both were heterozygous for the c.1451G>A (p.Gly484Glu) mutation in COL1A2. The father, a Thai boxer, had very mild osteogenesis imperfecta with no history of low-trauma bone fractures. Scanning electron micrography of the primary teeth with DI of the patient 2, and the primary teeth with DI of another OI patient with OI showed newly recognized dental manifestations of teeth with DI. Normal dentin and cementum might have small areas of ectopic mineralizations. Teeth affected with DI have well-organized ectopic mineralizations in dentin and cementum. The “French-fries-appearance” of the crystals at the cemento-dentinal junction and abnormal cementum have never been reported to be associated with dentinogenesis imperfecta, either isolated or osteogenesis imperfecta-associated. Our study shows for the first time that abnormal collagen fibers can lead to ectopic mineralization in dentin and cementum and abnormal cementum can be a part of osteogenesis imperfecta.

Cutis laxa with pulmonary emphysema, conjunctivochalasis, nasolacrimal duct obstruction, abnormal hair, and a novel FBLN5 mutation

We report on a 4‐year‐old girl with autosomal recessive cutis laxa, type IA, or pulmonary emphysema type (ARCL1A; OMIM #219100), with loose and wrinkled skin, mitral and tricuspid valve prolapse, conjunctivochalasis, obstructed nasolacrimal ducts, hypoplastic maxilla, and early childhood‐onset pulmonary emphysema. Mutation analysis of FBLN5 showed a homozygous c.432C>G missense mutation, and heterozygosity in the parents. This is predicted to cause amino acid substitution p.Cys144Trp. Conjunctivochalasis or redundant folds of conjunctiva and obstructed nasolacrimal ducts have not been reported to be associated with FBLN5 mutations. Histopathological study of the conjunctival biopsy showed that most blood vessels had normal elastic fibers. The gingiva appeared normal, but histologically elastic fibers were defective. Scanning electron micrography of scalp hair demonstrated hypoplastic hair follicles. The cuticles appear intact underneath the filamentous meshwork.

Expanding the phenotypic spectrum of acro‐cardio‐facial syndrome (ACFS): Exclusion of P63 mutation

Acro‐cardio‐facial syndrome (ACFS) is a rare autosomal recessive congenital malformation syndrome; consistent features include ectrodactyly, cleft lip/palate with minor facial anomalies, genital abnormalities, mental retardation, and growth retardation. Five cases have been reported. We report on a new patient with ACFS syndrome. In addition to the characteristic features of ACFS, the reported patient also has mild scoliosis, hemivertebrae and subclinical hyperthyroidism. These additional features may expand the phenotypic spectrum of the syndrome.

Role of leucine 341 in thyroid hormone receptor β revealed by a novel mutation causing thyroid hormone resistance

Leucine 341 has been predicted from crystal structure as an important residue for thyroid hormone receptor beta (TRβ) function, but this has never been confirmed in functional studies. Here, a novel p.L341V mutation as a cause of resistance to TRβ is described, suggesting an important role for L341 in TRβ function. In silico and in vitro studies confirmed that substituting L341 with valine and other non-polar amino acids impairs sensitivity of TRβ for triiodothyronine to various degrees, depending on their side-chain size and orientation.

Vitamin D deficiency and its relationship with cardiac iron and function in patients with transfusion-dependent thalassemia at Chiang Mai University Hospital

ABSTRACT Background: Vitamin D deficiency is common in patients with thalassemia. Vitamin D deficiency could be related to cardiac dysfunction. Increased parathyroid hormone (PTH) is also known to be associated with heart failure. Objectives: To determine the prevalence of Vitamin D deficiency and to explore the impact of Vitamin D deficiency on cardiac iron and function in patients with transfusion-dependent thalassemia. Method: A cross-sectional study in patients with Transfusion-dependent thalassemia was conducted. Patients with liver disease, renal disease, type 1 diabetes, malabsorption, hypercortisolism, malignancy, and contraindication for MRI were excluded. Calcium, phosphate, PTH, vitamin D-25OH were measured. CardiacT2* and liver iron concentration (LIC) and left ventricular ejection fraction (LVEF) were determined. Results Sixty-one (33M/28F) patients with Transfusion-dependent thalassemia were enrolled. The prevalence of Vitamin D deficiency was 50.8%. Patients with cardiac siderosis had tendency for lower D-25OH than those without siderosis (15.9 (11.7–20.0) vs. 20.2 (15.85–22.3) ng/mL); p = 0.06). Serum calcium, phosphate, PTH, LIC, cardiac T2*, and LVEF were not different between the groups with or without Vitamin D deficiency. Patients with Vitamin D deficiency had significantly lower hemoglobin levels compared to those without Vitamin D deficiency (7.5 (6.93–8.33) vs. 8.1 (7.30–8.50) g/dL; p = 0.04). The median hemoglobin in the last 12 months was significantly correlated with D-25OH. Cardiac T2* had significant correlation with PTH. Conclusion: Vitamin D deficiency is prevalent in patients with Transfusion-dependent thalassemia. Vitamin D level is correlated with hemoglobin level. Vitamin D status should be routinely assessed in these patients. Low PTH is correlated with increased cardiac iron. This study did not demonstrate an association between Vitamin D deficiency and cardiac iron or function in patients with Transfusion-dependent thalassemia.

Subtle inflammation: a possible mechanism of future cardiovascular risk in obese children

Purpose The risk of cardiovascular disease (CVD) has been shown to be associated with systemic inflammation in obese adults with metabolic syndrome (MetS). The aims of this study were to evaluate the prevalence of MetS and its relation to inflammatory markers in obese Thai children. Methods A cross-sectional study was conducted. Children with history of endogenous obesity, chronic diseases, drug ingestion, and any acute illness within 2 weeks prior to enrollment were excluded. Their fasting blood glucose (FBG) levels, oral glucose tolerance tests, insulin, lipid profiles, and selected inflammatory markers, including interleukin-6, tumor necrosis factor-alpha, and high-sensitivity C-reactive protein (hs-CRP) levels, were tested. Results In this study, 58 obese Thai children (female, 20; male, 38) with a mean body mass index z score of 5.1±2.2 were enrolled. The prevalence of MetS and prediabetes was 31% and 17.2%, respectively. None of the children had diabetes. FBG levels, 2-hour glucose levels, and lipid profiles were not statistically different between those with and without MetS. However, obese children with MetS had higher insulin levels and homeostasis model assessment of insulin resistance values. Elevated hs-CRP levels were found in 69% of the cases, although it was not statistically different between the 2 groups. Conclusion We described a substantial prevalence of MetS in Thai obese children. Regardless of MetS status, two-thirds of the obese children had elevated hs-CRP level, indicating subtle ongoing inflammatory process. This chronic inflammation feasibly predisposes them to CVD in the future, even in children without MetS.