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.

A novel MLL2 gene mutation in a Korean patient with Kabuki syndrome / 소아과

Kabuki syndrome (KS) is a rare genetic disease with a distinctive dysmorphic face, intellectual disability, and multiple congenital abnormalities. KS is inherited in an autosomal dominant manner. As the primary cause of KS, MLL2 mutations have been identified in 56-76% of affected individuals who have been tested, suggesting that there may be additional genes associated with KS. Recently, a few KS individuals have been found to have de novo partial or complete deletions of an X chromosome gene, KDM6A, which encodes a histone demethylase that interacts with MLL2. Nevertheless, mutations in MLL2 are the major cause of KS. Although there are a few reports of KS patients in Korea, none of these had been confirmed by genetic analysis. Here, we report a case of a Korean patient with clinical features of KS. Using direct sequencing, we identified a frameshift heterozygous mutation for MLL2: (c.5256_5257delGA;p.Lys1753Alafs*34). Clinically, the patient presented with typical facial features, and diagnosis of KS was based on the diagnostic criteria. While KS is a rare disease, other malformations that overlap with those found in individuals with KS are common. Hence, the diagnosis of KS by mutational analysis can be a valuable method for patients with KS-like syndromes. Furthermore, in the near future, other genes could be identified in patients with KS without a detectable MLL2 mutation.

Osteogenesis Imperfecta Type VI with Severe Bony Deformities Caused by Novel Compound Heterozygous Mutations in SERPINF1

Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders characterized by bone fragility, frequent fractures, and low bone mass. Dominantly inherited COL1A1 or COL1A2 mutations appear to be causative in the majority of OI types, but rare recessively inherited genes have also been reported. Recently, SERPINF1 has been reported as another causative gene in OI type VI. To date, only eight SERPINF1 mutations have been reported and all are homozygous. Our patient showed no abnormalities at birth, frequent fractures, osteopenia, and poor response on pamidronate therapy. At the time of her most recent evaluation, she was 8 yr old, and could not walk independently due to frequent lower-extremity fractures, resulting in severe deformity. No clinical signs were seen of hearing impairment, blue sclera, or dentinogenesis imperfecta. In this study, we describe the clinical and radiological findings of one Korean patient with novel compound heterozygous mutations (c.77dupC and c.421dupC) of SERPINF1.

Erratum: Clinical, radiologic, and genetic features of Korean patients with Mucopolysaccharidosis IVA / 소아과

This erratum is being published to correct of page 435 and Table 4.

Diagnosis and constitutional and laboratory features of Korean girls referred for precocious puberty / 소아과

PURPOSE: Precocious puberty is defined as breast development before the age of 8 years in girls. The present study aimed to reveal the diagnosis of Korean girls referred for precocious puberty and to compare the constitutional and endocrinological features among diagnosis groups. METHODS: The present study used a retrospective chart review of 988 Korean girls who had visited a pediatric endocrinology clinic from 2006 to 2010 for the evaluation of precocious puberty. Study groups comprised fast puberty, true precocious puberty (PP), pseudo PP, premature thelarche, and control. We determined the height standard deviation score (HSDS), weight standard deviation score (WSDS), and body mass index standard deviation score (BMISDS) of each group using the published 2007 Korean growth charts. Hormone tests were performed at our outpatient clinic. RESULTS: The PP groups comprised fast puberty (67%), premature thelarche (17%), true PP (15%), and pseudo PP (1%). Advanced bone age and levels of estradiol, basal luteinizing hormone (LH), and peak LH after gonadotropin-releasing hormone stimulation testing were significantly high in the fast puberty and true PP groups compared with the control group. HSDS, WSDS, and BMISDS were significantly higher in the true PP group than in the control group (P<0.05). CONCLUSION: The frequent causes of PP were found to be fast puberty, true PP, and premature thelarche. Furthermore, BMISDS were significantly elevated in the true PP group. Therefore, we emphasize the need for regular follow-up of girls who are heavier or taller than others in the same age group.

Clinical, radiologic, and genetic features of Korean patients with Mucopolysaccharidosis IVA / 소아과

PURPOSE: Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is rare lysosomal storage disorder caused by N-acetylgalactosamine-6-sulfatase (GALNS) deficiency. Only a few MPS IVA cases have been reported in the Korean literature; there is a paucity of research about clinical or radiologic findings for this disorder. Therefore, we studied clinical findings, radiological features, and genetic data of Korean MPS IVA patients for determining factors that may allow early diagnosis and that may thus improve the patients' quality of life. METHODS: MPS IVA was confirmed via assay for enzymatic activity of leukocytes in 10 patients. The GALNS gene was analyzed. Patients' charts were retrospectively reviewed for obtaining clinical features and evaluated for radiological skeletal surveys, echocardiography, pulmonary function test, and ophthalmologic test results. RESULTS: Nine patients had severe clinical phenotype, and 1 had an intermediate phenotype, on the basis of clinical phenotype criteria. Radiologic findings indicated skeletal abnormalities in all patients, especially in the hips and extremities. Eight patients had an odontoid hypoplasia, and 1 showed mild atlantoaxial subluxation and cord myelopathy. Genetic analysis indicated 10 different GALNS mutations. Two mutations, c.451C>A and c.1000C>T, account for 37.5% (6/16) and 25% (4/16) of all mutations in this samples, respectively. CONCLUSION: An understanding of the clinical and radiological features involved in MPS IVA may allow early diagnosis of MPS IVA. Adequate evaluations and therapy in the early stages may improve the quality of life of patients suffering from skeletal abnormalities and may reduce life-threatening effects of atlantoaxial subluxation.

Growth Hormone Treatment and Its Effect on Height in Pediatric Patients with Different Genotypes of Prader-Willi Syndrome

PURPOSE: Differences in phenotypes between the two most common subtypes of Prader-Willi syndrome (PWS) indicate that a distinct response to growth hormone (GH) treatment may exist. To test this hypothesis, we compared the results of GH treatment in individuals with PWS due to uniparental disomy (UPD) to those of individuals with deletions. METHODS: Sixty-five children with PWS who had been treated with GH for more than two years were included in this study. Twenty-one individuals were confirmed as having UPD and 44 individuals had a deletion. Height, body weight, body mass index (BMI), and insulin like growth factor-1 (IGF-I) measurements were recorded before GH treatment and at intervals of 12 months thereafter. RESULTS: After two years of GH therapy, no significant differences were noted for yearly improvements in height standard deviation scores (SDS) between the groups (second year SDS, 0.93 +/- 0.94; deletion, 0.84 +/- 1.31; UPD, P = 0.717). Body weight SDS, BMI SDS, and IGF-I SDS also showed no differences between the two groups. CONCLUSION: Our study showed no significant differences in yearly improvements in height SDS between the deletion and UPD groups, at least for the first two years.

Growth Hormone Treatment and Its Effect on Height in Pediatric Patients with Different Genotypes of Prader-Willi Syndrome

PURPOSE: Differences in phenotypes between the two most common subtypes of Prader-Willi syndrome (PWS) indicate that a distinct response to growth hormone (GH) treatment may exist. To test this hypothesis, we compared the results of GH treatment in individuals with PWS due to uniparental disomy (UPD) to those of individuals with deletions. METHODS: Sixty-five children with PWS who had been treated with GH for more than two years were included in this study. Twenty-one individuals were confirmed as having UPD and 44 individuals had a deletion. Height, body weight, body mass index (BMI), and insulin like growth factor-1 (IGF-I) measurements were recorded before GH treatment and at intervals of 12 months thereafter. RESULTS: After two years of GH therapy, no significant differences were noted for yearly improvements in height standard deviation scores (SDS) between the groups (second year SDS, 0.93 +/- 0.94; deletion, 0.84 +/- 1.31; UPD, P = 0.717). Body weight SDS, BMI SDS, and IGF-I SDS also showed no differences between the two groups. CONCLUSION: Our study showed no significant differences in yearly improvements in height SDS between the deletion and UPD groups, at least for the first two years.

Two Cases of Tension Pneumopericardium in Mechanically Ventilated Preterm Infants

Pneumopericardium is a rare form of neonatal air leakage. Tension pneumopericardium is much more infrequent, but can cause a cardiovascular deterioration with high mortality up to 80% and neurodevelopmental morbidity in half of the cases. We report two cases of preterm infants who successfully recovered from tension pneumopericardium that developed during mechanical ventilator assistance. The patients displayed a sudden increase in oxygen demand and subsequent cardiovascular deterioration. Immediate needle aspiration of the pneumopericardium performed after checking X-ray images rescued each of patient. Since the clinical symptoms are non-specific, clinicians' suspicion is most important when patients show sudden refractory cardiovascular collapse, especially in ventilator-assisted neonates. This life threatening complication demands instant diagnosis and intervention.