PURPOSE: Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is classified as Kallmann syndrome (KS) with anosmia and normosmic idiopathic hypogonadotropic hypogonadism (nIHH). This study was undertaken to investigate the clinical, endocrinological, and molecular characteristics in Korean patients with KS and nIHH. METHODS: Twenty-six patients from 25 unrelated families were included. Their clinical, endocrinological, and radiological findings were analyzed retrospectively. Mutation analysis of the GNRH1, GNRHR, KISS1, KISS1R, PROK2, PROKR2, TAC3, TACR3, FGF8, FGFR1, and KAL1 genes was performed in all patients. CHD7 and SOX10 were analyzed in patients with CHARGE (Coloboma, Heart defects, choanae Atresia, Growth retardation, Genitourinary abnormality, Ear abnormality) features or deafness. RESULTS: Of the 26 patients, 16 had KS and 10 had nIHH. At diagnosis, mean chronologic age was 18.1 years in males and 18.0 years in females; height SDS were -0.67+/-1.35 in males, -1.12+/-1.86 in females; testis volume was 2.0+/-1.3 mL; and Tanner stage was 1.5. There were associated anomalies in some of the KS patients: hearing loss (n=6) and congenital heart disease (n=4). Absence or hypoplasia of the olfactory bulb/sulci was found in 84.62% of patients with KS. Molecular defects in KAL1, SOX10, and CHD7 were identified in 5 patients from 4 families (16.0%, 4/25 pedigrees). After sex hormone replacement therapy, there were improvement in sexual characteristics and the sexual function. CONCLUSION: This study described the clinical, endocrinological, and molecular genetic features in IGD patients in Korea. Although the mutation screening was performed in 10 genes that cause IGD, molecular defects were identified in relatively small proportions of the cohort.
Cohort Studies ; Deafness ; Diagnosis ; Ear ; Female ; Gonadotropin-Releasing Hormone ; Hearing Loss ; Heart ; Heart Defects, Congenital ; Hormone Replacement Therapy ; Humans ; Hypogonadism* ; Immunoglobulin D ; Kallmann Syndrome* ; Korea ; Male ; Mass Screening ; Molecular Biology ; Nasopharynx ; Olfaction Disorders ; Retrospective Studies ; Testis ; Urogenital Abnormalities

The lupus anticoagulant-hypoprothrombinemia syndrome, characterized by presence of lupus anticoagulant with acquired factor II deficiency, is a rare disease entity often presented with acute bleeding episodes. A 15-year-old girl was hospitalized with 3 month history of menorrhagia and easy bruising. Prothrombin time (31.3 sec, normal value: 10-13 sec) and activated partial thromboplastin time (72.5 sec, normal value: 27.5-34.7 sec) were markedly prolonged and partially corrected after mixing with normal plasma. Decreased Factor II activity (4%, normal range: 79-131%) or prolonged dilute Russell's viper venom time (89.8 sec, normal value: 25.4-34.3 sec), was consistent with lupus anticoagulant-hypoprothrombinemia syndrome. Antinuclear antibody, anti-double strand-DNA antibodies and anticardiolipin antibodies were also positive. Bleeding diathesis tends to wax and wane while 5 years of treatment with steroid combined with immunosuppressants, however, there was no more active bleeding episodes. Several years after diagnosis, myocarditis, pericarditis, seizure was occurred, fulfilled the diagnostic criteria of systemic lupus erythematosus.
Adolescent ; Antibodies ; Antibodies, Anticardiolipin ; Antibodies, Antinuclear ; Diagnosis ; Disease Susceptibility ; Female ; Hemorrhage ; Humans ; Hypoprothrombinemias ; Immunosuppressive Agents ; Lupus Coagulation Inhibitor ; Lupus Erythematosus, Systemic ; Menorrhagia ; Myocarditis ; Partial Thromboplastin Time ; Pericarditis ; Plasma ; Prothrombin ; Prothrombin Time ; Rare Diseases ; Reference Values ; Seizures