Prevalence of idiopathic scoliosis in girls with central precocious puberty: effect of a gonadotropin-releasing hormone agonist

Purpose@#Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis and occurs in children between 10 to 18 years old, during periods of growth spurts and puberty changes. In patients with central precocious puberty (CPP), due to early growth spurt, AIS is expected to develop before 10 years of age. Both AIS and CPP are more common in girls than in boys. The aim of this study was to determine the prevalence of AIS in girls with CPP and to evaluate the effect of treatment with gonadotropin-releasing hormone (GnRH) agonists on progression of scoliosis in these patients. @*Methods@#We retrospectively reviewed medical records of 553 girls, 338 with CPP and 215 without CPP. Scoliosis angle was measured on the standing frontal radiograph of each patient according to the Cobb method. Patients with a Cobb angle of 10° or more were diagnosed with scoliosis. For girls with CPP, followup spine radiographs were collected 1 year after treatment with GnRH agonists. Progression of scoliosis before and after treatment was compared in terms of Cobb angle changes. @*Results@#AIS was more prevalent in girls that were affected by CPP compared tocontrols without CPP (11.5% vs. 6.0%, CPP girls vs. non-CPP girls, respectively, P=0.031). The peak serum luteinizing hormone level positively correlated with Cobb angle (R2=0.015, P=0.023) in the CPP group. No progression of scoliosis was observed in CPP girls after one year of GnRH agonist treatment. Additionally, the prevalence of scoliosis decreased in CPP girls after 1 year of the treatment. @*Conclusion@#We report that the prevalence of AIS is higher in girls with CPP than in non-CPP patients. A regular follow-up schedule for spine radiographs should be considered to reduce the risk of progression. Furthermore, GnRH agonist treatment for CPP may have a suppressive effect on progression of AIS.

Estrogen-mediated Height Control in Girls with Marfan Syndrome

This study evaluated the efficacy of a stepwise regimen of estradiol valerate for height control in girls with Marfan syndrome. Eight girls with Marfan syndrome who had completed estrogen treatment for height control were included. Estradiol valerate was started at a dose of 2 mg/day, and then was increased. The projected final height was estimated using the initial height percentile (on a disease-specific growth curve for Korean Marfan syndrome [gcPFHt]), and the initial bone age (baPFHt). After the estrogen treatment, the projected final height was compared to the actual final height (FHt). The median baseline chronological and bone age were 10.0 and 10.5 years, respectively. After a median of 36.5 months of treatment, the median FHt (172.6 cm) was shorter than the median gcPFHt (181.0 cm) and baPFHt (175.9 cm). In the six patients who started treatment before the age of 11 years, the median FHt (171.8 cm) was shorter than the median gcPFHt (181.5 cm) and baPFHt (177.4 cm) after treatment. The median differences between the FHt and gcPFHt and baPFHt were 9.2 and 8.3 cm, respectively. In two patients started treatment after the age of 11, the differences between FHt and gcPFHt, and baPFHt after treatment were -4 and 1.4 cm, and -1.2 and 0 cm for each case, respectively. A stepwise increasing regimen of estradiol valerate may be an effective treatment for height control in girls with Marfan syndrome, especially when started under 11 years old.

Birth seasonality in Korean Prader-Willi syndrome with chromosome 15 microdeletion

PURPOSE: Prader-Willi syndrome (PWS) is a well-known genetic disorder, and microdeletion on chromosome 15 is the most common causal mechanism. Several previous studies have suggested that various environmental factors might be related to the pathogenesis of microdeletion in PWS. In this study, we investigated birth seasonality in Korean PWS. METHODS: A total of 211 PWS patients born from 1980 to 2014 were diagnosed by methylation polymerase chain reaction at Samsung Medical Center. Of the 211 patients, 138 were born from 2000-2013. Among them, the 74 patients of a deletion group and the 22 patients of a maternal uniparental disomy (UPD) group were compared with general populations born from 2000 using the Walter and Elwood method and cosinor analysis. RESULTS: There was no statistical significance in seasonal variation in births of the total 211 patients with PWS (chi2=7.2522, P=0.2982). However, a significant difference was found in the monthly variation between PWS with the deletion group and the at-risk general population (P<0.05). In the cosinor model, the peak month of birth for PWS patients in the deletion group was January, while the nadir occurred in July, with statistical significance (amplitude=0.23, phase=1.2, low point=7.2). The UPD group showed the peak birth month in spring; however, this result was not statistically significant (chi2=3.39, P=0.1836). CONCLUSION: Correlation with birth seasonality was identified in a deletion group of Korean PWS patients. Further studies are required to identify the mechanism related to seasonal effects of environmental factors on microdeletion on chromosome 15.

Elevation of serum creatine kinase during methimazole treatment of Graves disease in a 13-year-old girl and a literature review of similar cases

We report a 13-year-old girl with Graves disease, who showed an increased level of serum creatine kinase (CK) accompanied by myalgia after methimazole (MMI) treatment. This patient developed muscular pain two weeks after MMI administration, along with increased CK levels. The level of thyroid hormone was within the normal range when she showed increased CK levels. After the MMI dose was decreased and levo-thyroxine was added, serum CK levels decreased to normal and the myalgia improved. The pathophysiologic mechanism of this effect has not yet been elucidated. An acute relatively hypothyroid state occurs secondary to antithyroid drug (ATD) administration in chronic hyperthyroidism, which may cause changes in the CK levels. In this report, we present a rare pediatric case, along with a literature review of similar cases. In the initial state of MMI treatment, myalgia should be detected and when it occurs, CK levels should be measured. The clinical strategy of monitoring CK levels with the aim of normalizing thyroid hormones is helpful in case of the development of adverse reactions, such as myalgia, during ATD treatment for Graves disease in children.

Impact of Enzyme Replacement Therapy on Linear Growth in Korean Patients with Mucopolysaccharidosis Type II (Hunter Syndrome)

Hunter syndrome (or mucopolysaccharidosis type II [MPS II]) arises because of a deficiency in the lysosomal enzyme iduronate-2-sulfatase. Short stature is a prominent and consistent feature in MPS II. Enzyme replacement therapy (ERT) with idursulfase (Elaprase(R)) or idursulfase beta (Hunterase(R)) have been developed for these patients. The effect of ERT on the growth of Korean patients with Hunter syndrome was evaluated at a single center. This study comprised 32 patients, who had received ERT for at least 2 yr; they were divided into three groups according to their ages at the start of ERT: group 1 (<6 yr, n=14), group 2 (6-10 yr, n=11), and group 3 (10-20 yr, n=7). The patients showed marked growth retardation as they got older. ERT may have less effect on the growth of patients with the severe form of Hunter syndrome. The height z-scores in groups 2 and 3 revealed a significant change (the estimated slopes before and after the treatment were -0.047 and -0.007, respectively: difference in the slope, 0.04; P<0.001). Growth in response to ERT could be an important treatment outcome or an endpoint for future studies.

Glycogen Storage Disease Presenting as Fetal Hydrops: A Case Report / 대한주산의학회잡지

Glycogen storage disease (GSD) is a group of heterogeneous disorders of glycogen metabolism that results in abnormal storage of glycogen in multiple organs. Clinical manifestations of GSD vary according to the basic enzyme defect. Only types II, IV, V or VII of GSD have been known to manifest in the infantile period. Of the 11 types of GSD, the congenital subtype of GSD type IV is characterized by severe neonatal hypotonia, multiple contractures, polyhydramnios, and fetal hydrops. We report a case of a patient born at a gestational age of 34 weeks and 3 days with fetal hydrops, joint contractures, and akinesia. Muscle biopsy results were highly indicative of GSD. This is the first case of suspected GSD in Korea presenting as fetal hydrops. The possibility of other disorders associated with glycogen metabolism should be considered in fatal fetal hydrops patients with severe hypotonia and arthrogryposis, and aggressive investigations such as muscle biopsy should be performed for early diagnosis.