Critical body fat percentage required for puberty onset: the Taiwan Pubertal Longitudinal Study.

PURPOSE: Prepubescent body fat percentage (BFP) is associated with puberty onset; however, the association between the timing of puberty onset and BFP remains unclear. This study aimed to determine whether and how the timing of puberty onset is associated with various anthropometric measures, and to investigate the critical time period of the BFP transition before and after puberty. METHODS: The Taiwan Pubertal Longitudinal Study (TPLS) has a multicenter, population-based prospective cohort and was established in July 2018 at 4 pediatric departments. We included girls aged 6-14 years and boys aged 9-17 years evaluated as having puberty onset and excluded those with precocious puberty diagnosis. The anthropometric measures were collected every 3 months. The main outcome was age at puberty onset. Data were analyzed between July 2018 and September 2020. RESULTS: For 153 girls and 83 boys, BFP was significantly related to puberty onset for girls. Longitudinal analysis revealed that BFP in the girls was reduced to less than 18% 6 months before puberty and rapidly increased by 2.85% over 3 months, then exceeding 20% before puberty onset. After puberty onset, BFP was no longer lower than 22%. CONCLUSIONS: BFP is an essential predictor of age at puberty onset. BFP first decreases and then begins to increase 3-6 months before puberty in girls. Parents and schools could monitor the BFP of prepubescent girls every 6 months to predict puberty onset.

Sources of cholesterol for testosterone biosynthesis in murine Leydig cells.

The sources of cholesterol for testosterone production were investigated in freshly isolated murine Leydig cells. In vitro stimulation with human CG (hCG) (0.2 IU/ml) caused a 75-fold increase in testosterone production. Leydig cells contained approximately equal amounts of free and esterified cholesterol (7.8 vs. 8.7 micrograms/mg protein). The total cholesterol content of cells stimulated for 4 h with hCG was significantly decreased compared with unstimulated cells (8.4 vs. 17.6 micrograms/mg protein); both free and esterified cholesterol decreased by about 50%. In unstimulated Leydig cells incubated with [14C]acetate for 12 h, the majority of incorporated [14C] was found in free and esterified cholesterol, whereas, in the hCG-stimulated cells, 80% of incorporated 14C was in testosterone. The activity of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase after 4 h in hCG-stimulated cells was 20% higher than in unstimulated cells (115.5 vs. 84.4 pmol/mg protein.min). However, by 6 h, HMG-CoA reductase activity doubled in the hCG-stimulated compared with unstimulated cells. By 12 h, HMG-CoA reductase activity in hCG-stimulated cells was 4 times the preincubation level and 8 times the 12-h level in unstimulated cells. HMG-CoA reductase activity induced by hCG was blocked by aminoglutethimide, an inhibitor of the cholesterol side-chain cleavage enzyme. Lovastatin, a potent inhibitor of HMG-CoA reductase, had no effect on unstimulated or hCG-stimulated testosterone production during a 12-h incubation. Murine high density lipoproteins (mHDL) increased HMG-CoA reductase activity in both unstimulated (29%) and hCG-stimulated (20%) cells. During a 6 h incubation, mHDL increased hCG-stimulated testosterone production by 20%, but had no effect on unstimulated testosterone production. These results suggest that murine Leydig cells store enough cholesterol and cholesteryl esters to support testosterone production for at least 12 h in vitro. Although mHDL does not have a major stimulatory effect on testosterone biosynthesis, it may be involved in the regulation of de novo cholesterol synthesis.

Kleine-Levin syndrome in a boy with Prader-Willi syndrome.

A 9 1/2-year-old Taiwanese boy with Prader-Willi syndrome had the following characteristics: difficulties with sucking, feeding and hypotonia during infancy, a dysmorphic face (triangular mouth, high arched palate, almond-shaped eyes and large head circumference with a relatively narrow bifrontal diameter), borderline intelligence, hypogonadism, hyperphagia, skin picking and truncal obesity. The boy experienced two hypersomnia episodes, at age 8 and 9 years, with both episodes lasting for 10 days. During the two episodes, he was found to have an exacerbated case of hyperphagia, pica, poor emotional control, stereotyped speech and agitated behavior upon awakening. After each episode, the boy had complete remission. Our findings show that the two episodes are compatible with Kleine-Levin syndrome. The relationship between the two syndromes, the Prader-Willi syndrome and the Kleine-Levin syndrome, deserves further study.

Galloway-Mowat syndrome in Taiwan.

We report on two Chinese female infants with multiple congenital anomalies: microcephaly, apparent porencephaly or encephalomalacia, developmental delay, minor facial anomalies, and contractural arachnodactyly. In the first patient, focal glomerulosclerosis was diagnosed histologically by percutaneous renal biopsy due to proteinuria with hematuria. Congenital hypothyroidism presenting with markedly low T3 and T4 was also noted. She died at age 5 months. The second patient had a very similar condition but less severe brain and kidney malformations. A variant of Galloway-Mowat syndrome is suspected.

Oral-facial-digital syndrome with Y-shaped fourth metacarpals and endocardial cushion defect.

We report on a boy with pseudo-cleft of the upper lip, cleft palate, bifid uvula, lobulated tongue, hypoplasia of the epiglottis, both preaxial and central polydactyly of the hands (Y-shaped fourth metacarpals), bilateral preaxial polydactyly of the feet, postaxial polydactyly of the left foot, hearing impairment, and congenital heart disease with endocardial cushion defect. These clinical manifestations resembled oral-facial-digital syndrome type II (OFDS II, Mohr syndrome) or type VI (Váradi syndrome), associated with an atrioventricular canal. Clinical variability of OFDS II has been observed repeatedly. To the best of our knowledge, this is the first reported case of OFDS II with Y-shaped fourth metacarpals. In addition to Y-shaped fourth metacarpals, Mohr syndrome plus atrioventricular canal and hypoplasia of the epiglottis may represent an additional subgroup of OFDS.

Jacobsen distal 11q deletion syndrome with a myelodysplastic change of hemopoietic cells.

We describe a male infant with unusual facial appearance, relative pancytopenia, bilateral simian creases, and an accessory nipple. Cytogenetic analysis showed deletion of the long arm of chromosome 11 [46,XY,del(11)(pter-->q23.2:)]. Bone-marrow study showed a myelodysplastic change of hemopoietic cells compatible with peripheral blood findings. Pachygyria of the temporal and frontal lobes was demonstrated by magnetic resonance image (MRI) of the brain. We present our findings in order to contribute to the information on 11q23 deletion.

Prognostic significance of left ventricular diastolic indexes in beta-thalassemia major.

OBJECTIVE: To define the prognostic significance of left ventricular diastolic function in patients with beta-thalassemia major by noninvasive M-mode echocardiography and Doppler measurements. DESIGN: Cohort analytic study. SETTING: A university hospital in Taipei, Taiwan. PATIENTS: Forty-five patients (age range, 4 to 25 years) with transfusion-dependent beta-thalassemia major followed up for 5 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: M-mode and Doppler echocardiography were used to determine the left systolic time interval; ejection fraction; left atrium emptying index; isovolumetric relaxation period; diastolic total period; the duration, slope, and height of the early diastolic flow-velocity peak; and the ratio between the heights of early and atrial diastolic flow-velocity peaks. All patients had normal systolic ventricular function initially, but impaired diastolic function developed, especially in the older age group who had more evidence of iron loading. In nine of those with abnormal diastolic total period (n = 10) and duration of the early diastolic flow-velocity peak (n = 12) values, regardless of age, congestive heart failure developed during the period of follow-up. Of these nine, four died within 2 years after the advent of heart failure and five remained compensated after anticongestive treatment and use of deferoxamine mesylate. The presence of an abnormal diastolic total period and duration of the early diastolic flow-velocity peak values correlated well with the prognosis. CONCLUSIONS: Left ventricular diastolic filling variables by echocardiography are important predictors of the outcome of patients with transfusion-dependent beta-thalassemia major and could provide useful measures in determining the effects of medication during long-term follow-up.

Optimization of walking in children.

Previous work demonstrated that adults naturally adopt a walking frequency to optimize physiological cost, symmetry, and stability. Furthermore, the optimal frequency is predictable using the force-driven harmonic oscillator (FDHO) model. However, no studies have established the developmental processes of optimization in children. Thus, the purposes of this study were to examine the predictability of the preferred stride frequency (PSF) and optimization features of 3- to 12-yr-old children using the FDHO model. Forty-five children and nine adults were measured for anthropometric data to calculate the predicted frequency. They later walked at three frequencies (PSF, PSF +25%, and PSF -25%) at a constant speed on a treadmill. The results indicated that the FDHO model was accurate in predicting the preferred frequency of children (prediction error < 0.07 s). We identified three stages of learning in the development of optimization: an early manifestation of sensitivity to resonant frequency, the subsequent development of ability to modulate walking frequency, and the final establishment of an adult optimization form at age seven. Our findings suggest that walking development may be determined by the dynamic cooperation of physiological, neural, and musculoskeletal systems with respect to the environmental context.

Growth of bifidobacteria in soymilk and their survival in the fermented soymilk drink during storage.

Growth of Bifidobacterium infantis CCRC 14633 and B. longum B6, in soymilk was investigated in the present study. It was found that soymilk could support the growth of both organisms tested. B. infantis grew better than B. longum in soymilk. Supplementation of bifitose (isomaltooligosccharie), glucose, lactose or galactose to soymilk increased the growth of B. infantis and B. longum as determined after 48 h of fermentation. On the other hand, addition of yeast extract, peptone, tryptone, casitone or N-Z-Case plus to soymilk enabled B. infantis to reach its maximum population in a shorter cultivation time of 24 h. Acid production by B. longum and B. infantis in soymilk was mainly non-growth associated, while in the yeast extract-supplemented soymilk, acid produced by B. infantis was found to be growth-associated. Populations of B. longum reduced more than did B. infantis in the prepared fermented soymilk drink during storage period. Viable population of both test organisms reduced less in the fermented drink held at 5 degrees C than at 25 degrees C. After a 10-day storage at 5 degrees C, viable B. infantis and B. longum reduced by 0.44 and 3.18 log CFU/ml, respectively, in the fermented drink. Addition of sucrose to the fermented drink resulted in an increased reduction of viable bifidobacteria during the storage period. This phenomenon was most prominent with B. infantis in the fermented drink held at 25 degrees C.

Angelman syndrome assessed by neurological and molecular cytogenetic investigations.

Angelman syndrome (AS) is characterized by severe psychomotor retardation, speech impairment, happy disposition with bursts of laughter, ataxia, convulsions, and some distinct physical anomalies. Correct diagnosis of AS is important because of its clinical implications, and once the disease is confirmed, familial genetic counseling becomes crucial. We evaluated 22 patients with a putative diagnosis of AS by both clinical and molecular cytogenetic analysis. A deletion of the region 15q11-13 could be identified cytogenetically in 11 cases by high-resolution technique (group I). Four additional cases were confirmed by fluorescence in situ hybridization (FISH) study with D15S11, SNRPN, D15S10, and GABRB 3 [Prader-Willi syndrome (PWS)/AS region probes] (group II). The common deletion of GABRB 3 was documented in those AS cases (n = 15) by FISH. The other 7 cases exhibited no deletion over 15q11-13 at either the cytogenetic or molecular level (group III). We compared the following associated neurological disorders: convulsions and abnormal EEG, microcephaly, sleep and behavior problems, brain anomalies proved by image studies, sexual precocity with pineal tumor among the three groups, as well as other clinical conditions including congenital heart disease, obesity, scoliosis, and hypopigmentation. In the present study, the differences in neurological and facial characteristics were not distinct among these groups. However, the associated conditions were more frequently observed in the patients with deletion than in those without deletion. The EEG features of AS appear to be less sufficient in helping identify patients at an early age before the clinical features become obvious. Therefore, a region involved in the major As phenotypes may contain only one or more tightly contiguous genes around the GABRB 3 locus, which may explain the clinical heterogeneity in AS.

Homocystinuria presenting as fatal common carotid artery occlusion.

A patient with homocystinuria presenting with fatal cerebral infarction that resulted from left common carotid artery occlusion is reported. This 13-year-old, healthy and intelligent girl presented with progressive cerebral infarction. Angiography revealed total occlusion of the left common carotid artery and stenosis of the right common carotid artery. Distal stenosis of bilateral vertebral arteries was also observed. Initially Takayasu arteritis with unusual manifestation was considered. However, later investigations revealed homocystinuria was the underlying cause. The sudden onset of fatal stroke as the initial clinical presentation of homocystinuria, as observed in this previous healthy teenager, is noteworthy. We suggest metabolic screening for homocystinuria when treating a patient with unusual vascular lesions.

MR imaging in patients with strabismus.

The patients with strabismus, including 8 with superior oblique paresis, 1 with inferior rectus paresis, and 1 with congenital constant exotropia, were examined with MR imaging at 1.5 tesla (T) or 0.5T with a surface coil. Abnormal findings of extraocular muscles were identified in 8 of the 10 patients and most of them were consistent with the clinical findings. Deviation of the optic nerves was noted in 5 patients. Coronal short repetition time (RT) and echo time (ET) images were used to measure the concerned extraocular muscles and the optic nerves. The differences in diameters between the concerned extraocular muscles of both the diseased and normal eyes were calculated. MR imaging is considered to be advantageous and can be favorably used to observe and measure the extraocular muscles and other intraorbital structures in patients with strabismus.

ESR spin trapping studies on the free radicals in gasphase of cigarette smoking.

Free radicals in the gasphase of cigarette smoke were determined by spin trapping agent PBN (N-tert-butyl-2-phenyl nitrone) and DMPO (5,5-dimethyl-1-pyrroline-oxide) on electron spin resonance spectrometer. They were identified according to the spectrum parameters calculated from the spectra. The free radicals mainly consist of alkoxyl and alkyl free radicals, of which alkoxyl free radicals make up 60-70% of the total spectral components. These free radicals are very active and reactive. They can damage cells and lead to some diseases. This work points out the importance of scavenging the free radicals of cigarette smoke to prevent diseases caused by them.

Active oxygen radicals produced by leukocytes of malignant lymphoma.

The electron spin resonance (ESR) spectra of active oxygen radicals produced during the respiratory burst of PMA-stimulated leukocytes and oxygen consumption are studied by ESR spin trapping and spin probe oxymetry for 31 times in 17 cases of malignant lymphoma. The results showed that the spectra produced from PMA-stimulated patients' leukocytes were predominantly spin adducts of DMPO-hydroxyl radicals (DMPO-OH). The decrease in oxygen consumption during respiratory burst suggested that respiratory burst function was inhibited. Kinetic observations of patient condition showed that respiratory burst and oxygen consumption were improved and even approached normal, when the patient was in remission or the condition was ameliorated. This paper is the first of its type and helps clarify the mechanism of malignant proliferation and metastasis.

Chromosomal rearrangements detected by FISH and G-banding.

Fluorescence in situ hybridization (FISH) using chromosome-specific DNA libraries as painting probes, locus-specific unique sequence (cosmid) probes, and Y-specific repetitive sequences was applied in the analysis of eighteen cases of chromosomal rearrangements of undetermined nature. FISH clarified the origin of the extra or translocated chromosome segments in seventeen patients, one with 2q+, two with 4q+, one each with 6p+, 7p+, 9q+, 10p+, 11q+ and 12p+, two with 13q+, and one each with 15q+, 17p+, 18p+, 20p+, 21p+ and Yq+, as well as the nature of a de novo supernumerary chromosome marker in a previously reported case. By G-banding and molecular cytogenetic studies of the family members, six cases were determined to have unbalanced translocations inherited from the carrier parent. The extra translocated genetic material may cause specific trisomic syndromes, including partial 6p21.3-p23, 9q32-q34.3, 13q32-q34, 15q24-q26, and 17p11.2-p13 trisomies in those patients. A translocated 21q segment on 12p was shown by a painting probe in a patient with Down features. A patient with cat cry syndrome resulting from a loss of the terminal segment of the short arm of chromosome 5 was confirmed by a cosmid probe showing de novo reciprocal translocation between chromosomes 5 and 18:t(5;18) (p13.3;p11.31). With FISH, the extra material on the rearranged chromosome could also be identified as duplicated or translocated. The FISH technique thus provides a method for the analysis of extra structurally abnormal chromosomes (especially in de novo cases), recognizable syndromes (contiguous gene syndromes) caused by translocated deletion from parental balanced chromosome rearrangements, and supernumerary marker chromosomes. FISH subsequent to G-banding is also of great help in the confirmation of preliminary abnormal G-banded karyotypes after a modified destaining procedure. In conclusion, the combination of G-banding and FISH is very useful in the accurate diagnosis of chromosomal rearrangements.

Amino acid and DNA analyses in a family with ornithine transcarbamylase deficiency.

Ornithine transcarbamylase (OTC) is a hepatic mitochondrial enzyme involved in the detoxification of ammonia by the urea cycle. OTC deficiency is an X-linked genetic disorder, usually causing neonatal or infantile hyperammonemia, coma and death. We attended a male newborn who had poor feeding since 30 hours of age, at which time, he then rapidly progressed to a comatose state. Hyperammonemia and liver dysfunction were noted. Analysis of plasma amino acids showed elevated levels of glutamine and alanine, but a decreased level of arginine and no citrulline. OTC deficiency was diagnosed by family history of early death of newborn males on the maternal side and characteristic biochemical findings. In addition, it was proved by Southern blot analysis of genomic DNA. Although OTC deficiency has been described as the most common inborn error of ureagenesis in humans, to our knowledge, this is the first report in a Chinese family confirmed by biochemical and DNA analyses.

Prader-Willi syndrome: clinical and molecular cytogenetic investigations.

Prader-Willi syndrome is characterized by hypotonia and feeding difficulties in the neonatal period, with the childhood development of hyperphagia leading to obesity, developmental delay, hypogonadism, short stature and small hands and feet. Correct diagnosis of Prader-Willi syndrome is important because of its clinical implications and the need for family genetic counseling. In order to determine the most efficient method of diagnosing the condition, we evaluated 37 patients with a putative diagnosis of Prader-Willi syndrome by both clinical and molecular cytogenetic analyses. Clinical evaluation showed that 25 patients fulfilled the diagnostic criteria for Prader-Willi syndrome. A deletion of the region 15q11.2-13 was cytogenetically identified in 20 patients using a high-resolution technique. Four additional cases were detected by fluorescence in situ hybridization (FISH) with the cosmid probes for D15S11, r-aminobutyric acid receptor beta 3 (GABRB3), small nuclear ribonucleoprotein-associated peptide N (SNRPN) or D15S10 (Prader-Willi/ Angelman syndrome region probes). The deletion of SNRPN was documented in 24 Prader-Willi syndrome patients. Only one additional patient with typical Prader-Willi syndrome features did not have any deletion over 15q11-13 at either the cytogenetic or molecular level. FISH provides a more reliable method than high-resolution chromosome analysis for the diagnosis of Prader-Willi syndrome. Associated conditions such as hypopigmentation, small-joint laxity, arachnodactyly, seizure disorder, optic atrophy, congenital heart disease, Perthes' disease, hirsutism, astigmatism/amblyopia, microcephaly and neuropsychiatric disturbances dictate the effects of a contiguous gene syndrome. Morbidity is high among patients with obesity and associated conditions. Appropriate genetic counseling should be given to the parents and dietary management should be helpful for patients with Prader-Willi syndrome.

Primed in situ (PRINS) labeling for rapid detection of numeric and structural chromosome anomalies.

Primed in situ (PRINS) labeling has been applied to replace the traditional fluorescence in situ hybridization (FISH) method for the detection of specific sequences in situ in several numerical and structural chromosome anomalies. PRINS is based on sequence-specific annealing in situ of an unlabeled DNA probe or oligonucleotide primer. The probe serves as a primer for chain elongation in situ, using the labeled nucleotides as substrate. An oligonucleotide, (CCCTAA) representing human telomeric sequences, was mixed with nucleotides, biotin-16-dUTP, and Taq DNA polymerase, and applied on metaphase slides with ring chromosomes 4, 13, 18, X and Y. Primers for alpha-satellite sequences specific for the centromeric regions of human chromosomes 13, 15, 18, X and Y were also used to characterize the nature and origin of unidentifiable supernumerary marker chromosomes. The specificity of PRINS in differentiating centromeric sequences of chromosome [3 from 21 which is not possible with FISH, was demonstrated. Absence of the telomeric sequences in all of the ring chromosomes was noted in normal and abnormal phenotypes. The results suggest a mechanism of ring formation, an end-to-end fusion after loss of the palindromic nucleotide sequences at the telomeres PRINS, a fast and sensitive method of detecting nucleic acid sequences in situ, may be a reliable technique for detecting chromosomal aneuploidies and some structural rearrangements.

Idiopathic juvenile osteoporosis: five-year case follow-up.

Juvenile osteoporosis is a disease of childhood and adolescence exhibiting marked clinical variability in bone change. The disease usually begins in the prepubertal period or even younger. A case of a Chinese boy suffering from back pain and generalized osteoporosis since 9 yr of age who spontaneously recovered at 14 yr of age when entering puberty is reported. The affected patient was clinically normal (as shown by X rays), until he fractured his left humerus. Metabolic studies indicated a negative calcium balance, but serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, calcifediol, calcitriol, cortisol and sex hormones were normal. X ray showed typical generalized osteoporosis with vertebral collapse. The disease markedly improved within 5 yr. No family history of inherited skeletal disorders or presenile osteoporosis was noted. The diagnosis of idiopathic juvenile osteoporosis was made.

Double aneuploidy with Down's-Klinefelter's syndrome.

The occurrence of double aneuploidy, ie, the existence of two chromosomal abnormalities in the same individual, is a relatively rare phenomenon. A 1-year-old boy with Down's syndrome resulting from de novo mosaic 21 trisomy with an additional X in the karyotype: 47,XXY/48,XXY,+21 (4%/96%) is reported. Besides the typical features of Down's syndrome, the patient did not have the commonly associated conditions (recurrent respiratory tract infections, congenital heart disease, thyroid or digestive tract problems). A molecular cytogenetic method with biotin-labeled probe D13Z1/D21Z1 was used to confirm the diagnosis and to clarify the status of Down's syndrome mosaicism which explained the milder stigmata of Down's syndrome in this case. The coexistence of Klinefelter's syndrome (47,XXY) also may have contributed to the development of normal height and micropenis in this patient. To our knowledge, this is the first case of Down's syndrome together with Klinefelter's syndrome in Taiwan.