Wen-Yu Tsai

An epidemiological study of nocturnal enuresis in Taiwanese children

Objective To estimate the prevalence of primary nocturnal enuresis (PNE) in Taiwanese children, and to examine factors associated with PNE and its severity.

Hypogonadotropic hypogonadism and hematologic phenotype in patients with transfusion-dependent beta-thalassemia

Objective To determine the prevalence and risk factors of hypogonadotropic hypogonadism in transfusion-dependent patients with thalassemia. Patients and Methods The authors examined 29 patients with thalassemia major aged 15 years or older. Luteinizing hormone-releasing hormone tests were performed and &bgr;-thalassemia mutations were analyzed by direct sequencing. Results The prevalence of hypogonadotropic hypogonadism was 72%. Failure of puberty was observed in 5 of 11 (45%) boys and 7 of 18 (39%) girls. Arrested puberty was noted in two boys (18%) and five girls (28%). Ten girls (56%) did not menstruate, two (11%) had regular menstrual cycles, one (6%) had irregular menstrual cycles, and five (28%) developed secondary amenorrhea. Twenty-one and eight patients had the &bgr;0/&bgr;0 and &bgr;0/&bgr;+ hematologic phenotypes, respectively. &bgr;0-thalassemia mutation alleles involved IVS II-654 (C-T), codons 41/42 (-TCTT), codons 27/28 (+C), and codons 17 (A-T). &bgr;+-thalassemia mutations alleles were -28 (A-G) and HbE (codons 26(GAG-AAG)). Hematologic phenotype (odds ratio, 28.50; P = 0.002) was the only risk factor identified in the logistic regression analysis. Conclusions In patients with thalassemia major, genetic differences may influence their susceptibility to hypogonadotropic hypogonadism, possibly as a result of differences in the amounts of blood transfused and/or their vulnerability to free radical damage. The hematologic phenotype is a main determinant of the severity of thalassemia major; hence, it may influence the need for and frequency of blood transfusion and the patients iron-overload status.

HLA DRB1/DQA1/DQB1 haplotype determines thyroid autoimmunity in patients with insulin‐dependent diabetes mellitus

OBJECTIVE Thyroid autoimmunity is frequently associated with insulin‐dependent diabetes mellitus (IDDM). The genetic factors which contribute to thyroid autoimmunity and IDDM have been described but vary between different races. We have therefore investigated the effect of class II HLA genes at both loci and the HLA haplotypes on the presence of autoimmunity in patients with IDDM in Taiwan.

Effect of Puberty Onset on Spontaneous Hepatitis B Virus e Antigen Seroconversion in Men

BACKGROUND Male predominance is a remarkable phenomenon in hepatitis B virus (HBV)-related liver disease. This study elucidated the effects of puberty on spontaneous hepatitis B virus e antigen (HBeAg) seroconversion in boys. METHODS One-hundred HBeAg-positive chronic HBV-infected males recruited at younger than 10 years of age who had been followed for >10 years were selected randomly from our long-term followed cohort into this study. Serum testosterone levels, androgen receptor exon-1 CAG repeat number and steroid 5alpha reductase type II (SRD5A2, valine vs leucine alleles) polymorphism were determined. Serial clinical data, HBV genotype, and spontaneous HBeAg seroconversion age were also analyzed. RESULTS Seventy-two subjects had spontaneous HBeAg seroconversion during the follow-up period. Subjects with serum testosterone levels > or =2.5 ng/mL at 15 years old (earlier-onset puberty, n = 87) had earlier HBeAg seroconversion (median age, 13.2 vs 22.5 years; hazard ratio = 2.95; P = .005), higher peak alanine aminotransferase levels when HBeAg positive (305.7 +/- 372.7 vs 154.8 +/- 126.0 IU/L; P = .006), and a greater HBV viral load reduction from 10 to 20 years of age (1.6 +/- 2.4 vs 0.2 +/- 1.4 log10 copies/mL; P = .009) than those with serum testosterone levels <2.5 ng/mL (later-onset puberty, n = 13). Valine allele carrier at the SRD5A2 V89L polymorphism was also associated with earlier spontaneous HBeAg seroconversion (median age, 11.7 vs 18.7 years; hazard ratio = 1.88; P = .028). CONCLUSION Earlier-onset puberty and increased SRD5A2 enzyme activity are associated with earlier HBeAg seroconversion, higher serum alanine aminotransferase levels, and a greater HBV viral load decrement in chronic HBV infected males.

Transcomplementation of HLA DQA1-DQB1 in DR3/DR4 and DR3/DR9 Heterozygotes and IDDM in Taiwanese Families

OBJECTIVE To study the human leukocyte antigen (HLA)-DQ heterodimers in the susceptible DR haplotypes for patients with insulin-dependent diabetes mellitus (IDDM) in Taiwan. RESEARCH DESIGN AND METHODS Extended class II HLA haplotypes were studied in 57 unrelated IDDM patients, 31 simplex IDDM families, and 105 unrelated control subjects recruited from the same area in Taiwan. Class II HLA genotyping was based on PCR-SSO DNA typing techniques. Extended class II HLA haplotypes were deduced unequivocally by the Taiwanese pedigree studies. RESULTS DR3/DR3, DR3/DR4, and DR3/DR9 genotypes were strongly associated with IDDM susceptibility in this population. In addition to the reported DR3/DR4 in Caucasians, the heterozygotic effect of DR3/DR9 for IDDM was remarkable in the Taiwanese population. Extended HLA haplotypes studies revealed that DRB1*0301/DQA1*0501/DQB1*0201, DRB1*0405/DQA1*0301/DQB1*0302, and DRB1*0405/DQA1*0301/DQB1*0401 were the susceptible haplotypes in this population. There were several hypothetical ways to produce susceptible HLA-DQ heterodimers to explain the susceptibility carried by DR3/DR4 and DR3/DR9 genotypes. Among all DR4 subtypes, only DRB1*0405 was associated with the increased risk of IDDM. CONCLUSIONS These data strongly suggest that the HLA-DR-associated IDDM susceptibility is most likely explained by the formation of the susceptible DQ heterodimers encoded by the DQA1/DQB1 either in cis or in trans.

Long-term outcome of hormonal status in Taiwanese children with Hashimoto’s thyroiditis

The objective of this prospective study was to evaluate both thyroid function in children with Hashimoto’s thyroiditis and the necessity of lifetime thyroxine replacement therapy. A total of 47 patients with goiter and positive thyroid auto-antibodies participated in the study. Serum thyroxine and thyrotropin levels and titers of thyroid auto-antibodies were checked regularly throughout the follow-up period. At the beginning of the study, 25 patients were diagnosed as euthyroid, but at the end of the study, 22 patients initially diagnosed with euthyroidism remained euthyroid, while eight patients with subclinical hypothyroidism and three patients with overt hypothyroidism had become euthyroid. Thus, of the 22 patients with thyroid dysfunction at diagnosis, subclinical or overt, 11 became euthyroid during the follow-up period. The effect of thyroxine treatment on thyroid auto-antibody titers was not significant. Conclusion: Our data shows that Hashimoto’s thyroiditis in children has a benign course and that thyroid function in one half of the patients with thyroid dysfunction at diagnosis reverts to normal. Careful follow-up of thyroid function is important in order to determine the necessity and timing of thyroxine replacement therapy.

Transient Pseudohypoparathyroidism as a Cause of Late-onset Hypocalcemia in Neonates and Infants

BACKGROUND/PURPOSE Transient pseudohypoparathyroidism is a rare cause of late-onset hypocalcemia in neonates and infants. The purpose of this study was to investigate the clinical presentation and natural course of transient pseudohypoparathyroidism in neonates and infants. METHODS From 1995 to 2006, 21 patients under 3 months of age were admitted to our department because of late-onset neonatal hypocalcemia. Among these, five were noted to have transient hypocalcemia, hyperphosphatemia and elevated serum parathyroid hormone levels. Their clinical data, biochemical findings and natural course were thoroughly analyzed. RESULTS All five patients were boys with increased neuromuscular irritability as their initial clinical manifestation. Initial biochemical data showed calcium 1.5 +/- 0.16 mmol/L, phosphorus 9.6 +/- 1.5 mg/dL, intact parathyroid hormone 182 +/- 93 pg/mL and tubular reabsorption of phosphorus 94.8 +/- 3.7%. Two of the patients had magnesium deficiency. After reduction of phosphorus intake and supplementation with calcium and/or magnesium as indicated, the biochemical derangements resolved in 28 +/- 3 days. CONCLUSION Neuromuscular irritability is usually the initial clinical presentation of transient pseudohypoparathyroidism. Aside from delayed renal maturation, pseudohypoparathyroidism is also caused by magnesium deficiency. Such a disturbance usually resolves before 3 months of age.

The Effects of Gonadotropin Releasing Hormone Analogue Therapy on Girls with Gonadotropin-dependent Precocious Puberty

BACKGROUND/PURPOSE It has been reported that gonadotropin releasing hormone analogue (GnRHa) therapy can improve the adult height of patients with gonadotropin-dependent precocious puberty. The purpose of this study was to evaluate the effect of GnRHa on the adult height of girls with gonadotropin-dependent precocious puberty and the adverse effects of such therapy. METHODS Between 1989 and 2006, 11 girls with gonadotropin-dependent precocious puberty who had been treated with GnRHa and reached their adult height were enrolled in the present study. Follow-up studies of bone age, pelvic sonography and GnRH test were done regularly during the period of treatment. All patients had bone mineral density examined at least 2 years after completion of GnRHa therapy. RESULTS GnRHa therapy was initiated at the age of 8.0 +/- 1.5 years. The predicted adult height immediately before GnRHa therapy was 146.7 +/- 4.8 cm (-2.3 +/- 0.9 standard deviation [SD]). The duration of GnRHa therapy was 4.7 +/- 1.8 years. The adult height of the patients was 156.3 +/- 4.3 cm (-0.6 +/- 0.8 SD), which is similar to their target height of 157.0 +/- 4.5 cm (-0.5 +/- 0.8 SD). The uterine sizes and gonadotropin responses to GnRH stimulation were well suppressed during treatment. Menstruation resumed 9.2 +/- 5.9 months after the discontinuation of treatment in these patients. Forty-five percent of patients had lumbar bone mineral density less than 1 SD below that of normal young Taiwanese adults in the Taipei region. CONCLUSION GnRHa therapy can improve the adult height of patients with gonadotropin-dependent precocious puberty. However, 45% of patients had decreased bone accretion during therapy.

Arachnoid cyst with GnRH-dependent sexual precocity and growth hormone deficiency

The coexistence of gonadotropin-releasing hormone (GnRH)-dependent sexual precocity and growth hormone deficiency in patients with arachnoid cysts is rarely reported, and its pathogenesis is not well recognized. This report describes an 11-year-old female who had a huge intracranial arachnoid cyst with initial symptoms and signs of sexual precocity. Her brain magnetic resonance imaging revealed distorted hypothalamus with a thin and stretched pituitary stalk. After treatment with cysto-peritoneal shunting and gonadotropin-releasing hormone analogue, her puberty was arrested and subnormal growth rate was observed. Catch-up growth was detected after growth hormone therapy. Hence, coexistence of gonadotropin-releasing hormone-dependent sexual precocity and growth hormone deficiency in this patient was confirmed.

Mitochondrial cytopathy combined with Fanconi's syndrome.

Severe muscle weakness in Fanconis syndrome is rarely the result of mitochondrial cytopathy. We describe a rare case of a 9-year-old male with early onset of Fanconis syndrome. He developed severe proximal muscle weakness exacerbated by hypokalemia and hypophosphatemia in childhood. The muscle biopsy revealed increased accumulation of abnormal mitochondria and fat droplets in histochemical stains and electron microscopy. Mitochondrial cytopathy cannot be excluded in Fanconis syndrome with late onset of muscular impairment. Long-term follow-up of his clinical course is suggested to understand the natural history of this unusual case.