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SummaryContext Hypoparathyroidism is characterised by hypocalcaemia, hyperphosphataemia, and low or inappropriately normal parathyroid hormone (PTH) levels. Idiopathic or genetic drivers are the predominant causes of hypoparathyroidism in paediatric-age patients. Objective This study investigated the aetiology and clinical course of primary hypoparathyroidism in infancy and childhood. Subjects and measurements This study included 37 patients (23 males, 14 females) with primary hypoparathyroidism diagnosed prior to 18 years of age. We analysed aetiologies, initial presentation, age at diagnosis, endocrine and radiological findings, and outcomes. Results The median age at presentation was 1.7 months (range 1 day–17 years), and the mean follow-up duration was 7.0 ± 5.3 years (range 0.5–16.8 years). Our cohort included 22 cases (59.5%) of 22q11.2 microdeletion syndrome. Other aetiologies included hypoparathyroidism-deafness-renal dysplasia syndrome (5/37, 13.5%) and one patient each with autoimmune polyglandular syndrome type 1, Kearns–Sayre syndrome, and Kenny–Caffey syndrome. The remaining 7 (18.9%) patients were classified as idiopathic hypoparathyroidism cases. Among the 15 patients who underwent brain imaging, 5 (33.3%) had basal ganglia calcification. Among the 26 patients examined by renal imaging, 5 (19.2%) had either nephrocalcinosis or a renal stone. After 11 months of calcium or calcitriol supplementation, 16 patients (43.2%) discontinued medication. The final PTH levels were significantly higher in patients with transient hypoparathyroidism than those with permanent hypoparathyroidism. Conclusions Identification of the genetic aetiologies of hypoparathyroidism makes it possible to predict patient outcomes and provide appropriate genetic counselling. Long-term treatment with calcium and calcitriol necessitates monitoring for renal complications. This article is protected by copyright. All rights reserved.

Kawasaki disease (KD) is an acute self-limited vasculitis of infants and children that manifests as fever and signs of mucocutaneous inflammation. Coronary artery aneurysms develop in approximately 15-25% of untreated children. Although the etiology of KD is largely unknown, epidemiologic data suggest the importance of genetic factors in the susceptibility to KD. In order to identify genetic variants that influence KD susceptibility, we performed a genome-wide association study (GWAS) using Affymetrix SNP array 6.0 in 186 Korean KD patients and 600 healthy controls; 18 and 26 genomic regions with one or more sequence variants were associated with KD and KD with coronary artery lesions (CALs), respectively (p

Kawasaki disease is an acute, self-limited vasculitis of infants and children, manifest as fever and signs of mucocutaneous inflammation. Treatment with high-dose immunoglobulin reduces systemic inflammation and prevents coronary artery lesions in Kawasaki disease. In this study, we investigated the possible association of the major histocompatibililty complex (MHC) region for the susceptibility to Kawasaki disease using an MHC panel of 2360 single nucleotide polymorphism (SNP) markers. Analysis of data obtained from screening MHC-specific SNP chips with 48 case and 90 control subjects revealed five candidate loci with significance levels of uncorrected p0.01. However, only one candidate locus (HLA-G) was confirmed to have a significant association with Kawasaki disease (rs2523790, odds ratio [OR] = 3.00, 95% confidence interval [95% CI] = 1.14-7.91, uncorrected p = 0.0263) in the replication study using 44 new case subjects and the previous 90 controls. In the fine mapping of the HLA-G locus, in particular, a nonsynonymous SNP (C/A) of the HLA-G gene (rs12722477, Leu134Ile) was significantly associated with Kawasaki disease (OR = 3.23, 95% CI = 1.12-9.32). A subgroup analysis showed that this association was more apparent in patients with coronary artery aneurysms (OR = 4.02, 95% CI = 1.23-13.19). Therefore, our results indicate that HLA-G may play a crucial role for the susceptibility to Kawasaki disease.

BACKGROUND Up to the current time, diagnosis of bone marrow (BM) involvement in non-Hodgkin lymphoma (NHL) has been based on morphologic findings. Polymerase chain reaction (PCR) for antigen receptor gene rearrangements has the potential to increase the detection sensitivity of minimal degrees of BM involvement. The authors therefore assessed PCR-based clonalities of BM concurrently with morphology from 170 cases with NHL and evaluated the usefulness of comparative analysis of clonalities between bilateral BMs and the lymph node and the clinical significance of PCR based clonalities of BM. METHODS Bilateral BM clot sections of 170 cases and 47 lymph nodes were tested for immunoglobulin heavy chain gene rearrangement or T-cell receptor gamma gene rearrangement according to the B- or T-lineage of the lymph node. RESULTS When compared with morphology, the results of PCR showed an unexpectedly low positive concordance rate of 61.0% for B-cell NHL and 57.1% for T-cell NHL. When the clonality of BM was compared with that of lymph nodes in B-cell NHL, bilateral clonalities of BM showed high concordance with the clonality of the lymph nodes. PCR-based clonality did not show significant impact on survival. CONCLUSIONS Morphology remains the gold standard in the evaluation of BM involvement by NHL. Although the comparative analysis of BM clonality and that of the lymph nodes is considered a valuable tool that increases the reliability of clonality, PCR-based clonality of BM does not significantly add to the sensitivity of diagnosing BM involvement by NHL. Cancer 2002;94:3073–82. © 2002 American Cancer Society. DOI 10.1002/cncr.10584

Essential thrombocythemia (ET) is a clonalmyeloproliferative disorder that can rarely transform into acute leukemia in 1∼5% of cases. A recent study has found that a significant proportion of leukemic cases from ET were associated with a cytogenetic abnormality (17p deletion). Herein, we report two cases of acute myeloid leukemic transformations harboring a 17p abnormality from a series of 119 ET patients. The first case, a 48-year-old female, developed acute myeloid leukemia with maturation (AML-M2) ac- companying myelodysplasia was diagnosed 6.1 years after the initial diagnosis of ET. She was treated with hydroxyurea. Her karyotype showed a monosomy 17. The second case, a 61-year-old male, developed acute megakaryoblastic leukemia (AML-M7) with a very complex hyperdiploidy including addition of 17p13 that developed 6.5 years after the initial diagnosis. He was treated with hydroxyurea and anagrelide. The immunohistochemistry showed p53 overexpression in both cases. Our cases support the specificity of chromosome 17 abnormality and p53 overexpression in acute leukemic transformation from ET.

Hypoplastic variant of acute leukemia is rare and almost always has a myeloid phenotype. We retrospectively investigated the incidence, clinico-laboratory characteristics, and clinical outcomes of hypoplastic acute myeloid leukemia (HAML), which was defined by bone marrow hypocellularity (less than 40% of cellularity in trephine biopsy) with increase of bone marrow blasts (20% or more) and peripheral blood leukopenia (less than 4,000/μl). Between 1989 and 2005, 740 patients were diagnosed as having AML at the Asan Medical Center and the definition of HAML was satisfied in 24 (3.3%). Patients with HAML showed a higher median age (67.5 vs. 44.0 years; P