RESUMO
OBJECTIVE: A cohort of women with phenylketonuria (PKU) were selected to explore the impact of phenylalanine (Phe) levels and other factors on congenital heart defects (CHDs), microcephaly, and development of their offspring. STUDY DESIGN: Three hundred fifty-four women with PKU were followed up weekly with diet records, blood Phe levels, and sonograms obtained at 18 to 20 and 32 weeks' gestation. At birth, 413 offspring were examined and followed up at 6 months and annually by means of Bayley Mental Developmental Index and Psychomotor Developmental Index tests at 1 and 2 years. The women had Wechsler Adult Intelligence Scales and DNA testing. RESULTS: Thirty-one offspring had CHDs; of these, 17 also had microcephaly. Mean Phe levels at 4 to 8 weeks' gestation predicted CHDs (P <.0001). An infant with a CHD had a 3-fold risk of having microcephaly when the mother had higher Phe levels (P =.02). The Bayley Mental Developmental Index and Psychomotor Developmental Index scores correlated with both CHDs (P =.037 and.0015, respectively) and microcephaly (P =.0001 for both). No direct relationship to the PKU mutation was found. CONCLUSION: None of the women whose offspring had CHDs had blood Phe levels in control during the first 8 weeks of gestation. Women with PKU need to be well controlled on a low-phenylalanine diet before conception and throughout pregnancy.
Assuntos
Deficiências do Desenvolvimento/etiologia , Cardiopatias Congênitas/etiologia , Microcefalia/etiologia , Fenilcetonúrias/complicações , Complicações na Gravidez , Adulto , Desenvolvimento Infantil/fisiologia , Estudos de Coortes , Dieta , Feminino , Seguimentos , Genótipo , Idade Gestacional , Humanos , Recém-Nascido , Inteligência/fisiologia , Prontuários Médicos , Mutação/genética , Fenilalanina/efeitos adversos , Fenilalanina/sangue , Fenilalanina/uso terapêutico , Fenilcetonúrias/genética , Fenilcetonúrias/prevenção & controle , Cuidado Pré-Concepcional , Gravidez , Complicações na Gravidez/prevenção & controle , Desempenho Psicomotor/fisiologia , Fatores de Risco , Ultrassonografia Pré-NatalRESUMO
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
A collaborative study of diet discontinuation in children with PKU was initiated in 1973. Children treated with the phenylalanine-restricted diet since early infancy were randomly assigned to continue or discontinue dietary therapy at age 6 years after parental consent was obtained. The 115 children participating in this study range in age from 8 to 13 years. At 6 years of age, the IQ of continuers and discontinuers was 101 and 97, respectively. At 8 years, WISC Full-Scale IQ scores adjusted for mean differences on the 6-year Stanford-Binet IQ were 101 for continuers and 98 for discontinuers (P = 0.075). School performance measured by the Wide Range Achievement Test showed significant differences on reading (3.9 vs 3.2) and spelling (3.3 vs 2.9) grade placement, although scores were above actual grade placement (2.7 vs 2.6) for both groups. Continuers and discontinuers were not different in arithmetic scores, with performance at grade placement of 2.7 and 2.6 respectively. Although these data are preliminary in nature, they suggest that subtle changes in cerebral function may occur in children with PKU in whom the phenylalanine diet has been discontinued.