Kevalee Unachak

Microcephalic osteodysplastic primordial dwarfism with severe microdontia and skin anomalies: confirmation of a new syndrome.

We report two related Thai children having a new syndrome of microcephalic osteodysplastic primordial dwarfism (MOPD). The findings which classify them as having MOPD include IUGR, microcephaly, prominent nose and nasal bridge, small pinnae, short stature, cone‐shaped and ivory‐epiphyses, delayed bone age, slender long bones, and abnormal pelvis. The findings that distinguish them as having newly recognized syndrome consist of severe microdontia, malformed teeth, single‐rooted or rootless teeth, severely hypoplastic alveolar bone, café au lait spots, acanthosis nigricans, and areas of hypo‐ and hyperpigmented skin. The reported patients appear to have the same condition as the family reported by Kantaputra [2002: Am J Med Genet 111:420–428]. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148‐7299/suppmat/index.html.

Robinow (fetal face) syndrome: report of a boy with dominant type and an infant with recessive type.

The cases of two patients with Robinow fetal face syndrome, an 11-year-old Thai boy and a newborn Caucasian girl, are described. The Thai boy had the characteristics typical of the dominant type of the syndrome with a few newly recognized signs, including communicating hydrocephalus, underdeveloped sinuses, short roots of the teeth, narrow and thick-floored pulp chambers, hypoplastic nipples, absent middle phalanges of the second to fifth toes, cone-shaped epiphyses of the second and fourth fingers and fifth toes, single creases of the fourth and fifth fingers, clinodactyly of the third fingers, dysmorphic umbilicus, and shawl scrotum. The girl had anomalies typical of the recessive type of the syndrome. She also had capillary hemangioma at the tip of her nose and hypoplastic fourth metatarsal bones, which are the newly recognized features of the recessive type. Infrequently reported clinical manifestations of the syndrome are discussed.

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.

Infantile osteopetrosis in four Thai infants

Four Thai infants, aged between 4 and 23 months, had progressive abdominal distension, pallor and delayed or regressed developmental milestones, with age at onset of 1 month, 3 months, 4 months and 1 month, respectively. Clinical findings consisted of growth and developmental retardation, anemia, frontal bossing, marked hepatosplenomegaly, and hearing and visual impairment. Laboratory findings revealed moderate anemia, leukocytosis and thrombocytopenia. The radiographic findings comprised generalized sclerosis of all bones, including the cranial base, and obliteration of the medullary canals and trabecular patterns. The first and second patients, who had swelling of the wrist joints and prominent costochondral junctions, had hypophosphatemia, elevated levels of serum alkaline phosphatase, and metaphyseal flaring on their radiographs, which was consistent with infantile osteopetrosis complicated by rickets. After Stoss therapy, there were biochemical and radiological responses suggesting vitamin D deficiency in the first patient, but not in the second. The third patient, who had hypocalcemia, hypophosphatemia and normal levels of serum alkaline phosphatase, received vitamin D at 3000 units per day, without improvement. Despite frequent blood transfusions, all patients continued to deteriorate and were finally lost to follow-up. Rickets should be identified and treated at the onset, because treatment of rickets leads to improvement in well-being and an adequate clinical response to bone marrow transplantation.

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.

A HIV-infected adolescent with polycystic ovary syndrome

We report a case of polycystic ovary syndrome in a 15-year-old human immunodeficiency virus-infected female on highly active antiretroviral therapy who developed hypertriglyceridemia, hyperinsulinemia due to insulin resist ance, and hyperandrogenism. Ultrasonography showed multiple small follicles at the right ovary and lobulated follicles at the l eft ovary. Treatment of polycystic ovary syndrome included insulin sensitizing agents (metformin, pioglitazone) and a contraceptive for hyperandrogenism. We also encouraged life style modificati on including regular exercise and dietary fat restriction. She attained menarche 1 month after initiation of treatment.