A Rare Case of Transformation of Childhood Myelodysplastic Syndrome to Acute Lymphoblastic Leukemia

Transformation of MDS into ALL during childhood is extremely rare. We report a rare case of an 8-yr-old girl who presented with refractory cytopenia of childhood (RCC) that transformed into ALL only 3 months after the diagnosis of childhood MDS. Although no cytogenetic abnormalities were observed in conventional karyotype and FISH analysis, we found several deletions on chromosomes 5q, 12q, 13q, and 22q. Partial homozygous deletion of the RB1 gene was observed on microarray analysis, with the bone marrow specimen diagnosed as ALL. This is the first case report of transformation of ALL from childhood MDS in Korea. We also compared the clinical, cytological, and cytogenetic features of 4 previously reported childhood MDS cases that transformed into ALL.

The effectiveness of tacrolimus and minidose methotrexate in the prevention of acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation in children: a single-center study in Korea / 대한혈액학회지

BACKGROUND: Knowledge of the roles of tacrolimus and minidose methotrexate (MTX) in the prevention of acute graft-versus-host disease (aGVHD) in pediatric allogeneic hematopoietic stem cell transplantation (HSCT) is limited. We retrospectively evaluated the engraftment status, incidence of aGVHD and chronic GVHD (cGVHD), and toxicities of tacrolimus and minidose MTX in aGVHD prophylaxis in children undergoing allogeneic HSCT. METHODS: Seventeen children, who underwent allogeneic HSCT and received tacrolimus and minidose MTX as GVHD prophylaxis from March 2003 to February 2011, were reviewed retrospectively. All the patients received tacrolimus since the day before transplantation at a dose of 0.03 mg/kg/day and MTX at a dose of 5 mg/m2 on days 1, 3, 6, and 11. RESULTS: Of the 17 patients, 9 received human leukocyte antigen (HLA)-matched related donor transplants, and 8 received HLA-matched, or partially mismatched unrelated donor transplants. The median time for follow-up was 55 months. The incidence of aGVHD in the related and unrelated donor groups was 22.2% and 42.9%, respectively. cGVHD was not observed. To maintain therapeutic blood levels of tacrolimus, the younger group ( or =8 years) (P=0.0075). The adverse events commonly associated with tacrolimus included hypomagnesemia (88%), nephrotoxicity (23%), and hyperglycemia (23%). CONCLUSION: Tacrolimus and minidose MTX were well tolerated and effective in GVHD prophylaxis in pediatric patients undergoing allogeneic HSCT. Children <8 years of age undergoing HSCT required increased doses of tacrolimus to achieve therapeutic levels.

A Case of Apert Syndrome with a P253R Mutation on FGFR2 Exon VIII

Apert syndrome is a rare congenital anomaly characterized by craniofacial malformations and severe symmetrical syndactyly of fingers and toes. This syndrome is caused by a genetic mutation; the S253 mutation is common, though the P253R mutation is not as frequent. Common symptoms include skeletal malformations, poor joint mobility, eye and ear problems, cleft palate, and orthodontic and other dental problems. We report a case of an infant with the common morphological features of Apert syndrome. Interestingly, she was found to have the P253R mutation in FGFR2 exon VIII, which has been less commonly observed in Korea. A brief review of the literature is included.

A Case of Infantile Hepatic Hemangioendothelioma Incidentally Detected during the Evaluation of Galactosemia

Galactosemia is a group of inherited enzyme deficiencies characterized by increase in the blood galactose levels. This condition may be associated with deficiencies of galactose-1-phosphate uridyl transferase, galactokinase, or uridine diphosphate galactose-4-epimerase. However, the elevated galactose identified by neonatal screening tests has several other possible etiologies, including hepatic hemangioendothelioma, hepatic hemangioma, and patent ductus venosus with hypoplasia of the portal vein. We report a 13-day-old Korean male with hepatic hemangioendothelioma, which was incidentally detected during the evaluation for suspected galactosemia. Laboratory studies revealed that mildly elevated levels of galactose, galactose-1-phosphate and alpha-fetoprotein, at the time of admission, were gradually decreased to the normal range over the 6 months of observation. Ultrasonography showed a well-defined heterogeneous hypoechoic mass in the liver, and magnetic resonance imaging study showed multiple enhanced mass lesions, which was compatible with the diagnosis of a hepatic hemangioendothelioma. Thus, hepatic imaging, especially ultrasonography, should be performed if neonatal screening suggests galactosemia.

The Effectiveness of Once-daily Intravenous Busulfan as a Conditioning Regime for Hematopoietic Stem Cell Transplantation in Children with Acute Myelogenous Leukemia / 대한혈액학회지

BACKGROUND: There have recently been some reports suggesting that once-daily intravenous busulfan (IV Bu) as a conditioning regime for hematopoietic stem cell transplantation (HSCT) possibly reduces the toxicities without influencing the clinical outcome as compared with the traditional 4 times daily dosage schedule. We report here on the clinical outcome of once-daily IV Bu as a conditioning regime for HSCT in children with AML at a single treatment center. METHODS: We retrospectively analyzed nine AML children who received HSCT with using the once-daily IV Bu (110~130 mg/m2 on 4 consecutive days) conditioning regimen at the Department of Pediatrics, Pusan National University Hospital from 2003 to 2007. RESULTS: The median age at HSCT was 8.25 years. As for the conditioning regimens, the HLA-matched sibling peripheral HSCT (N=4) was Flu/Bu, the CBT and unrelated BMT (N=4) was Flu/Bu/ATG and the autologous HSCT (N=1) was Bu/Cy. There was only one case of primary graft failure in an unrelated donor CBT recipient. The median time to neutrophil engraftment was 14 days and the median time to platelet engraftment was 19 days. The transplant-related toxicities were acceptable; there were no case with CNS toxicity and VOD was observed in two cases (1 mild case of VOD and 1 moderate case of VOD). Acute GVHD was noted in two cases (1 case of grade I and 1 case of IV). With a median follow up of 33 months, there were two cases of relapse and two cases of death. CONCLUSION: Once-daily IV Bu as a conditioning regimen for HSCT in children with AML was well tolerated and convenient with relatively moderate toxicities, but additional studies are needed to determine the therapeutic efficacy and pharmacokinetics of once-daily IV Bu in children who are undergoing HSCT.

Change of neutrophil count after treatment of intravenous immunoglobulin in children with idiopathic thrombocytopenic purpura / 소아과

PURPOSE: The aim of this study was to investigate the incidence and course of neutropenia following intravenous immunoglobulin (IVIG) therapy in children with idiopathic thrombocytopenic purpura (ITP). METHODS: From January 2001 to June 2006, fifty-four patients with ITP were enrolled in this study. Forty-two of 54 patients were treated with IVIG, while the other 12 were treated with anti-D immunoglobulin (Anti-D Ig). Post-treatment absolute neutrophil counts (ANC) were compared between patients who received IVIG and those who received Anti-D Ig. Comparison of post-treatment ANC between patients who treated with two different IVIG regimens (400 mg/kg/day for 5 days and 1 g/kg/day for 2 days) was also performed. RESULTS: Pretreatment ANC were not significantly different between the two treatment groups. After treatment with IVIG, 32 out of 42 patients (76.2%) showed more than 50% decrease of ANC from the baseline. On the other hand, only 2 out of 12 patients (16.7%) showed more than 50% decrease of ANC from the baseline after treatment Anti-D Ig. No significant difference was observed in the decline of ANC between the first IVIG treatment (42 patients) and repeated IVIG treatment groups (7 patients). There was no statistical difference in post-treatment ANC between patients who treated with two different IVIG regimens. The neutropenia induced by IVIG had resolved spontaneously in 38 out of 39 patients (97%) after several days. CONCLUSION: Neutropenia following IVIG administration may not be an uncommon finding in children with ITP. It seems to be transient and self limited.

A Case of the Fanconi Syndrome with Nephrocalcinosis

Fanconi syndrome is a generalized functional disorder of the proximal tubule of the kidney and is characterized by aminoaciduria, glycosuria, hyperphosphaturia, dehydration, rickets, and growth failure. Nephrocalcinosis and hypercalciuria are rare manifestations of Fanconi syndrome. There is no case report of Fanconi syndrome complicated with nephrocalcinosis and hypercalciuria in Korea. A 6-year-old boy presented with genu valgum and waddling gaits for about 3 years. There was no family history of renal disease and his physical examination was normal except for genu valgum and corrected cleft lip and palate. Laboratory investigations showed generalized aminoaciduria, glycosuria, hyperphosphaturia, hypercalciuria, and low-molecular weight proteinuria including beta2-microglobulin. Serum 25-OH vitamin D3 was within the normal range, and 1,25-(OH)2 vitamin D3 was elevated. Bilateral renal medullary hyperechogenicity was demonstrated by ultrasonography. Analysis of the CLCN5 gene revealed no mutation. Here we describe a boy with Fanconi syndrome complicated with nephrocalcinosis and discuss the differential diagnosis.

Immunization Practices in Children with Renal Disease: A Survey of the Members of Korean Society of Pediatric Nephrology

PURPOSE: There is no scientific basis for an immunization policy for children with renal disease who have increased risk of infection in Korea. As an initial step in approaching this problem, this survey of pediatric nephrologists was undertaken to determine the current recommendations of practicing pediatric nephrologists. METHODS: Questionnaires were sent to the members of Korean Society of Pediatric Nephrology via mail and E-mail. The questionnaire was designed to obtain information about the immunization practice of basic vaccination schedule for nephrotic syndrome, the side effects after vaccination and the immunization practice about recommended vaccines for children with renal disease. RESULTS: Questionnaires were sent to 56 pediatric nephrologists. 35 replies were received (response rate: 62.5%). Almost of the respondents (82.8%) reported practicing at university hospital. All respondents reported modified vaccination schedule. 65.7% of the respondents immunized nephrotic children with live vaccines some time later after discontinuation of corticosteroids treatment and 57.1% of respondents immunized them with killed vaccines during medication of low doses of corticosteroids. Respondents experienced relapse of nephrotic syndrome after vaccination are nine, lack of vaccine efficacy are three and infection by organisms of live vaccines are two. 71.4% of respondents reported vaccinating children with renal disease for hepatitis B, pneumococcus and influenza during medication of low doses of corticosteroids. But There is few difference of the rates of respondents vaccinating them for Hemophilus influenzae type b between during medication of low doses of corticosteroids and after discontinuation of corticosteroids treatment (45.7% vs 42.9%). Almost of respondents reported vaccinating renal failure children without immunosuppression for hepatitis B, pneumococcus, influenza and H. influenzae type b (54.3-77.1%). CONCLUSION: Pediatric nephrologists practiced modifying vaccination schedules for children with renal disease in Korea and there was variation according to the progression of disease and the doses of corticosteroids. It is necessary to establish the immunization guideline for children with renal disease through the prospective studies.

A Case of Wernicke's Encephalopathy which Occurred During Chemotherapy in a Child with Acute Myeloblastic Leukemia

Wernicke,s encephalopathy(WE), a neurological disorder caused by thiamine deficiency, is characterized by the triad of ocular symptoms, ataxia, and mental confusion. More than 90% of the cases are observed in chronic alcoholics. Other conditions less frequently associated with WE are anorexia nervosa, prolonged parenteral nutrition, hemodialysis, uremia, hyperemesis gravidarum, gastroplasty for morbid obesity, and acquired immunodeficiency syndrome(AIDS). One of the rare diseases associated with WE is tumors of the lymphoid-hemopoietic systems. We experienced a case of WE in a 15-year-old girl presented with bilateral horizontal nystagmus, bilateral abducens nerve palsy, mental confusion, disorientation, and ataxia after suffering anorexia, persistent vomiting, and watery diarrhea for 30 days following chemotherapy for acute myeloblastic leukemia. The serum thiamine level was 13.4 ng/mL(normal : 18.4-53.1). Brain MR T2-weighted image revealed a high signal intensity lesions bilaterally at the medial thalamus, pons, tectum, mammilary body, lateral wall of third ventricle, and putamen. Bilateral abducens nerve palsy, ataxia, and mental confusion improved dramatically following thiamine 100 mg/day replacement for 4 days. After two monthly follow-up, she was left with a residual fine bilateral horizontal nystagmus. We confirmed this case by clinical symptoms, brain MR findings, low thiamine level, and clinical response following thiamine replacement, and report with a brief review of the literature.

A Case of Achalasia Complained of Neurologic Symptom / 대한소아소화기영양학회지

Achalasia is a rare motor disorder of the esophageal smooth muscle in which the lower esophageal sphincter dose not relax properly with swallowing, and the normal peristalsis of the esophageal body is replaced by abnormal contractions. Achalasia has been described as party of several distinct multisystem syndromes suggesting a generalized neuromuscular disorder as the mode of origin. An 11-year-old female was admitted because of paresthesia on the trunk and both legs for 5 days. She had suffered from chest discomfort, dysphagia, postprandial vomiting, and weight loss for 6 months. She was diagnosed as having achalasia by means of the esophagography and esophageal manometry. Her chest discomfort, dysphagia and vomiting much improved after the endoscopic balloon dilatation. The authors present an 11-year-old female with achalasia complained of paresthesia and sucessfully managed by the balloon dilatation.

Factors Related to Weight Changes after Valproic Acid Administration in Epileptic Children Treated with Valproic Acid / 대한간질학회지

PURPOSE: Weight gain is a common side effect of valproic acid (VPA) that leads to discontinuation in some patients, but its incidence and correlates have been rarely studied in children. This study was undertaken to investigate factors related to weight changes in children treated with VPA. METHODS: We have analyzed mean weight standard deviation score (SDS) retrospectively and interviewed 39 childhood epileptic patients attending Pusan National University Hospital on VPA monotherapy followed over 36 months. Putative risk factors including sex, age, duration of VPA administration, mean weight SDS score at diagnosis, dose of VPA administration, seizure type (generalized or partial), and etiology (idipathic or symptomatic) were statistically analyzed. RESULTS: Thirty nine children (23 boys, 16 girls) were treated with VPA monotherapy. Mean age of patients at diagnosis was 6.18+/-3.74 years, and mean weight SDS at diagnosis was 0.54+/-1.17. After the administration of VPA, mean weight SDS was significantly increased (p<0.05). Increase in mean weight SDS was significant in children with negative mean weight SDS at diagnosis, idiopathic epilepsy, partial seizure, and also significant in children below 1 year old. Mean weight SDS was well correlated with the dose of VPA administration after 18 months of VPA monotherapy (p<0.05). CONCLUSIONS: Our data indicate that VPA monotherapy significantly increased body weight of patients treated for epilepsy. It will be better, if possible, combination therapy of VPA with other antiepileptic drugs (such as vigabatrin, carbamazepine, gabapentin) which can lead to weight gain.

Growth Pattern of Children on Medication with Anticonvulsants

PURPOSE: This study was performed to investigate the growth pattern of epileptic children on medication with anticonvulsants. METHODS: We measured the weight, height and head circumference of 219 epileptic children on medication with anticonvulsants through the review of the medical records, compared these with those of the control group as means of Standard Measurement of Body Growth for Korean Chidren and Adolescence reformed at 1998 and analyzed this data according to sex, age at the start of medication, duration of medication, the cause of epilepsy, the type of seizure and the number of anticonvulsants. RESULTS: The weight and height at the start of medication with anticonvulsants had no difference from those of the control group according to sex, age at the start of medication, the cause of epilepsy, the type of seizure and the number of anticonvulsants, but the head circumference at the start of medication was smaller than that of the control group(P<0.05), especially in children aged 1 to 6 years(P<0.005) and in children with symptomatic epilepsy(P<0.001). The increase of weight, height and head circumference had no difference from those of the control group according to sex, age, duration of medication, the cause of epilepsy, the type of seizure and the number of anticonvulsants. CONCLUSION: The increase of weight, height and head circumference of epileptic children on medication with anticonvulsants had no difference from those of normal children.

A Case of Neonatal Myocardial Infarction with Structurally Normal Coronary Arteries

Myocardial infarction in the newborn is usually seen in association with congenital heart disease, for example anomalous origin of the left coronary artery, tricuspid atresia and left ventricular outflow obstruction. However, it is very rare in infants with structurally normal coronary artery. In infants with structurally normal hearts and coronary arteries, the most common causes of myocardial infarction are perinatal asphyxia and thromboembolic occlusion. We experienced a case of neonatal myocardial infarction with structurally normal coronary arteries complicated sepsis and hypoglycemia. The diagnosis of myocardial infarction was made by EKG and increase of plasma myocardiac enzyme. We report this case with related literature.