RESUMO
This study was conducted to determine whether there is a genotype/phenotype correlation between aspects of cognitive, neurologic, and ovarian outcome in patients with galactosemia and the Q188R mutation of the galactose-1-phosphate uridyltransferase gene. The results showed that the Q188R mutation was found in 72% of alleles: 38 patients were homozygous and 21 were heterozygous for Q188R; eight patients did not have the mutation. The mean Broad Cognitive score for the group homozygous for Q188R was 75 (SD = 16), which was not statistically different from the outcome for the heterozygous group (mean score, 67; SD = 25) or the negative group (mean score, 88; SD = 21). Tremor, ataxia, and dysmetria were found in 12 subjects, and there was no association with Q188R status. Similarly, there was no association of this mutation with the development of primary amenorrhea (8 subjects) versus secondary amenorrhea (found in 14 women). Our findings suggests that the variability of outcome for patients with classic galactosemia cannot be explained by Q188R status alone, at least with regard to cognitive functioning, presence of neurologic symptoms, and timing of the onset of ovarian failure.
Assuntos
Cognição , Galactosemias/genética , Transtornos dos Movimentos/etiologia , Mutação , Insuficiência Ovariana Primária/etiologia , UTP-Hexose-1-Fosfato Uridililtransferase/genética , Adolescente , Adulto , Criança , Feminino , Galactosemias/complicações , Galactosemias/psicologia , Homozigoto , Humanos , Masculino , Transtornos dos Movimentos/genética , Insuficiência Ovariana Primária/genéticaRESUMO
As part of the Hemophilia Growth and Development Study, we investigated the impact of human immunodeficiency virus (HIV) infection on statural growth, weight gain, and skeletal and sexual maturity in more than 300 boys with moderate to severe hemophilia, of whom 62% were infected with HIV. Age-adjusted height and weight were reduced in the HIV-infected subjects (p < 0.001). However, mean weight for height and triceps skin-fold thickness of the infected-boys closely resembled those of the uninfected group. In HIV-infected boys, height for age was positively related to the CD4+ lymphocyte count when the count was < 200 cells/mm3. Age-adjusted serum testosterone levels did not differ by HIV status, but in the infected participants the mean age-adjusted bone age was significantly reduced (p = 0.038) and the distribution of Tanner stages, adjusted for age, differed significantly (p = 0.003). The probability of advancing one or more Tanner stages in the first study year was significantly slowed in HIV-infected boys more than 14 years of age (p = 0.0003). We conclude that linear growth was significantly impaired in boys with hemophilia and HIV infection, but the wasting of malnutrition was not found. The delays in bone age and pubertal maturation strongly suggest that part of the growth failure seen in acquired immunodeficiency syndrome can be attributed to pubertal delay. We speculate that the lack of demonstrable difference in age-adjusted testosterone concentrations might reflect subtle differences in the pattern of secretion of testosterone or in the concentration of sex-hormone binding globulin.
Assuntos
Infecções por HIV/fisiopatologia , Hemofilia A/fisiopatologia , Puberdade Tardia/fisiopatologia , Adolescente , Adulto , Estatura , Peso Corporal , Criança , Infecções por HIV/sangue , Infecções por HIV/complicações , Hemofilia A/sangue , Hemofilia A/complicações , Humanos , Estudos Longitudinais , Masculino , Maturidade Sexual , Testosterona/sangueRESUMO
Forty children and adults with classic galactosemia had vertebral bone density determined by standard quantitative computed tomography at 3.4 to 44.2 years of age. Compared with age- and sex-matched control subjects, patients with galactosemia had diminished bone density (p = < 0.001). Prepubertal patients of both sexes had bone density determinations below those of the control group (p = 0.008); similar findings were seen in postpubertal patients as well (women, p = 0.001; men, p = 0.008). Women receiving replacement estrogen-progestin therapy for premature ovarian failure had abnormal bone density (136.3 +/- 17.3 mg/cm3 vs 166.0 +/- 17.5 mg/cm3 for control subjects; p = 0.002); patients with evidence of ovarian insufficiency not receiving replacement sex steroids had even lower bone density (92.4 +/- 14.3 mg/cm3 vs 160.2 +/- 20.2 mg/cm3 for control subjects; p < 0.001). Calcium intake for the entire galactosemia group was 540 +/- 344 mg/day. Calcium intake correlated positively with bone density in women given exogenous estrogen (r = 0.87; p = 0.002) and in men (r = 0.74; p = 0.009). Thus the diminished mineralization of bones appears to be another abnormality associated with galactosemia. The results of our study suggest that this is likely secondary to abnormal levels of sex steroids in female patients, low calcium intake, and perhaps an intrinsic defect in the normal galactosylation of the collagen matrix of bone caused by the enzyme defect. Strategies to improve bone formation should be considered to diminish morbidity in patients with this inborn error of metabolism.
Assuntos
Densidade Óssea/fisiologia , Cálcio/deficiência , Galactosemias/metabolismo , Hipogonadismo/metabolismo , Adolescente , Adulto , Cálcio/metabolismo , Criança , Pré-Escolar , Dieta , Feminino , Galactosemias/diagnóstico por imagem , Galactosemias/fisiopatologia , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
The relationship between long-term blood glucose control and albuminuria in type 1 diabetes was investigated in 42 male and 58 female patients who had had diabetes mellitus for more than 7 years. Their mean (+/- SD) age and diabetes duration were 18.6 +/- 3.6 and 12.1 +/- 3.5 years, respectively. For periods of observation ranging from 1 to 6 years (mean 4.4 +/- 1.5), hemoglobin A1c (HbA1c) was measured two to six times yearly (mean of 8.8 +/- 3.9 determinations per patient). Albumin excretion rate (AER) was measured in single-void urine samples two to four times in 93 patients and once in the other seven patients. The 52 patients with mean HbA1c no more than 9.0% had significantly lower mean AER than those whose HbA1c was greater than 9.0% (20.1 +/- 24.6 vs 265 +/- 1005 mg/gm Cr, p less than 0.001). Only five (9.6%) of these 52 patients had elevated AER values (greater than 40 mg/gm Cr), whereas 21 (43.7%) of 48 patients whose mean HbA1c was greater than 9.0% had elevated AER values (p less than 0.001). Six male but no female patients had mean AER values greater than 300 mg/gm Cr. The 74 patients with normal AER had significantly lower mean HbA1c values than the 26 with elevated AER (8.6 +/- 1.5 vs 10.1 +/- 1.6%, p less than 0.001). These results support the contention that maintenance of HbA1c levels at no more than 9% (one and one-half times the upper limit of normal) will significantly decrease the likelihood that diabetic nephropathy will develop.
Assuntos
Albuminúria/epidemiologia , Glicemia/análise , Diabetes Mellitus Tipo 1/epidemiologia , Adolescente , Adulto , Albuminúria/complicações , Albuminúria/urina , Criança , Doença Crônica , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , PrevalênciaRESUMO
To evaluate the dynamics of growth hormone (GH) secretion in subjects with normal stature and to determine whether a correlation exists between height and the quantity of GH secreted, we determined the 24-hour GH concentration by measuring GH levels every 30 minutes in 27 boys and 19 girls of normal height, 7 to 18 years of age, of whom 24 were prepubertal and 22 in various stages of puberty. Spontaneous GH secretion had wide variations, with values ranging from less than 1.0 to 67.0 micrograms/L. In prepubertal children the highest GH levels were usually noted during sleep; in pubertal subjects the highest values were distributed almost equally between sleep and wake hours. In all subjects, GH secretion appeared to decrease before meals, followed by an increase after meals. Most indexes of GH secretion and insulin-like growth factor I levels were significantly greater in pubertal than in prepubertal subjects (p less than 0.002), and in both groups the GH concentration was significantly greater during sleep (p less than 0.005). In all groups the 24-hour GH concentration correlated significantly with the area under the GH curve, 24-hour GH pulse amplitude, and GH concentration and peak GH level during sleep and wake hours (P less than 0.0001); 24-hour GH concentrations correlated with insulin-like growth factor I levels only when the entire group of 46 subjects was considered (p less than 0.01). There were no significant correlations between 24-hour GH concentration and the subjects' age, bone age, height (SD score), weight (SD score), or body mass index. We conclude that in subjects with normal stature, mean 24-hour GH concentrations vary considerably and in the low range overlap with values reported in hypopituitarism.
Assuntos
Ritmo Circadiano , Hormônio do Crescimento/metabolismo , Adolescente , Fatores Etários , Criança , Ingestão de Alimentos , Feminino , Hormônio do Crescimento/sangue , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Puberdade , Fatores Sexuais , Sono/fisiologiaAssuntos
Galactosemias/fisiopatologia , Nucleotidiltransferases/metabolismo , Ovário/fisiopatologia , UTP-Hexose-1-Fosfato Uridililtransferase/metabolismo , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Galactosemias/enzimologia , Galactosefosfatos/sangue , Humanos , Lactente , Uridina Difosfato Galactose/sangueRESUMO
To assess whether growth-retarded children with a stimulated growth hormone (GH) level greater than 10 ng/mL have an abnormality in spontaneous GH secretion, we measured GH levels every half hour for 24 hours in 50 children 2.7 to 17 years of age. Growth rate was subnormal in all. Mean 24-hour GH concentration ranged from 1.2 to 7.7 ng/mL, and was significantly greater in pubertal than in prepubertal children (P less than 0.01). In both groups, GH concentration during sleep was significantly greater than during wakeful hours (P less than 0.0005); 24-hour GH concentration correlated significantly with sleep-induced GH peak. A decrease in 24-hour GH concentration and sleep-induced GH peak were noted in four pubertal children with stimulated GH less than 15 ng/mL. A progressive and significant increase in somatomedin C (SmC) level was noted with increasing age and sexual development. No correlations were found between 24-hour GH concentration and rate of growth, age, or bone age. Serum SmC values correlated significantly with age and bone age (P less than 0.01), and with 24-hour GH concentration only in prepubertal children (P less than 0.05). A strong correlation between SmC and growth rate was noted only in pubertal children (P less than 0.01). Growth velocity increased significantly during GH therapy regardless of the 24-hour GH concentration. Our results indicate that in children with growth retardation there is a wide variation in 24-hour GH concentration and a significant increase in GH concentration during puberty; the GH concentration during nocturnal sleep, rather than an entire 24-hour GH concentration, can be used for evaluation; during puberty the SmC level reflects sexual development more than GH reserve; and GH therapy appears to increase growth velocity in both non-GH-deficient and partially GH-deficient short children.