RESUMEN
BACKGROUND/OBJECTIVES: Little information is available as to the cause of increased thickening of the intima-media of the carotid artery (cIMT) in the pediatric population. Therefore, cIMT was compared in obese adolescents and normal-weight controls, and associations between cIMT and lipid and non-lipid cardiovascular risk factors were assessed. SUBJECTS/METHODS: Subjects included 61 obese non-diabetic male and female volunteers aged 12-18 years inclusive with a body mass index (BMI) >95th percentile for age and 2-h blood glucose <200 mg dl(-1) matched to 25 normal-weight control volunteers with normal glucose levels. Each subject underwent a 2-h glucose tolerance test and measurement of hemoglobin A1c, ultrasensitive C-reactive protein, fasting insulin, blood lipids, visceral, subcutaneous abdominal and hepatic fat, and cIMT. RESULTS: Maximum cIMT was 0.647±0.075 mm in the obese subjects versus 0.579±0.027 mm in normal-weight controls (P<0.001). There was no difference in maximum cIMT between male and female subjects. There were significant correlations between maximum cIMT and BMI z-score, 2-h glucose, fasting insulin, homeostasis model assessment (HOMA), total low-density lipoprotein (LDL) cholesterol, very LDL cholesterol, high-density lipoprotein (HDL) cholesterol, HDL2 cholesterol, HDL3 cholesterol, triglycerides, remnant lipoprotein cholesterol, intermediate-density lipoprotein cholesterol, lipoprotein(a), apoprotein B100, abdominal subcutaneous fat volume, visceral fat volume and hepatic phase difference. On multiple regression analysis, visceral fat was the most significant predictor of maximum cIMT. Two-hour blood glucose, HOMA and systolic blood pressure were also significant predictors of maximum cIMT. CONCLUSIONS: cIMT was increased in the obese adolescents compared with the normal-weight-matched controls. Visceral fat was a key predictor of arterial wall thickening in these subjects. The results suggest that the focus of cardiovascular disease prevention in the adolescent obese should be visceral obesity, and not blood lipids or lipid subclasses.
Asunto(s)
Aterosclerosis/etiología , Grosor Intima-Media Carotídeo/efectos adversos , Resistencia a la Insulina , Grasa Intraabdominal/patología , Obesidad Infantil/complicaciones , Adolescente , Aterosclerosis/patología , Aterosclerosis/prevención & control , Glucemia/metabolismo , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Niño , Femenino , Prueba de Tolerancia a la Glucosa , Hemoglobina Glucada/metabolismo , Humanos , Insulina/sangre , Lípidos/sangre , Masculino , Obesidad Infantil/patología , Obesidad Infantil/prevención & control , Factores de RiesgoRESUMEN
BACKGROUND/OBJECTIVES: Adult studies suggest that intra-hepatic fat predicts 2-h blood glucose levels and type 2 diabetes, and may have a role in the development of insulin resistance. Our study objective was to explore relationships between intra-hepatic fat and (i) blood glucose levels and (ii) insulin resistance determined by homeostasis model assessment (HOMA) in a group of obese adolescents. METHODS: Subjects were 61 obese non-diabetic male and female volunteers aged 12-18 years inclusive with a body mass index >95th percentile for age and 2-h blood glucose <200 mg dL(-1) . Each subject underwent 2-h glucose tolerance testing and measurement of haemoglobin A1c, ultrasensitive C-reactive protein and fasting insulin. Visceral, subcutaneous abdominal and intra-hepatic fat were determined by magnetic resonance imaging. Intra-hepatic fat was measured by gradient echo chemical shift imaging. RESULTS: Alanine aminotransferase levels and hepatic phase difference were not significant correlates of fasting or 2-h glucose. In a multiple regression model including hepatic phase difference and visceral fat volume, visceral fat volume was the sole predictor of HOMA. CONCLUSIONS: This study provides no support to the notion that intra-hepatic fat has a role in the regulation of fasting blood glucose, 2-h postprandial blood glucose or systemic insulin resistance.
Asunto(s)
Diabetes Mellitus Tipo 2/etiología , Hígado Graso/etiología , Resistencia a la Insulina , Obesidad Infantil/complicaciones , Adolescente , Glucemia/metabolismo , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/prevención & control , Ayuno , Hígado Graso/metabolismo , Hígado Graso/fisiopatología , Femenino , Prueba de Tolerancia a la Glucosa , Hemoglobina Glucada/metabolismo , Humanos , Insulina/sangre , Grasa Intraabdominal/patología , Masculino , Obesidad Infantil/sangre , Obesidad Infantil/fisiopatología , Periodo PosprandialRESUMEN
To assess the importance of postprandial lipemia and delayed chylomicron clearance as early atherogenic risk factors, 60 male offspring of parents with early coronary artery disease (CAD) and 41 controls were administered a fat-rich meal containing vitamin A. There were no significant differences between CAD-positive (CAD+) offspring and CAD-negative controls for areas under the postprandial curves for triglyceride and plasma, chylomicron, and chylomicron remnant retinyl palmitate. Older CAD+ offspring, aged 31-45 yr, had significantly increased very low density lipoprotein (VLDL) cholesterol, VLDL triglyceride, VLDL apoprotein B, and areas under postprandial curves for triglyceride and plasma, chylomicron, and chylomicron remnant retinyl palmitate than younger CAD+ offspring, aged 15-30 yr. Correcting for waist/hip ratio eliminated significant differences between the two groups for VLDL and areas under the triglyceride and chylomicron remnant curves, but this was not the case for the insulin sensitivity index. We conclude that neither increased postprandial lipemia nor abnormalities of chylomicron clearance are important early atherogenic risk factors in this population. An increase in age is associated with increased VLDL and postprandial lipemia and decreased chylomicron remnant clearance. This is due mainly to an increase in the waist/hip ratio and not to a change in insulin sensitivity.
Asunto(s)
Colesterol/sangre , Quilomicrones/metabolismo , Enfermedad Coronaria/genética , Padres , Periodo Posprandial , Triglicéridos/sangre , Adolescente , Adulto , Análisis de Varianza , Estudios de Casos y Controles , Enfermedad Coronaria/sangre , Diterpenos , Humanos , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Valores de Referencia , Ésteres de Retinilo , Vitamina A/análogos & derivados , Vitamina A/sangreRESUMEN
A 2-year-old boy had acute fever, malaise, and somnolence with hepatomegaly, increased blood ammonia content (338 microM), high SGOT, low blood glucose content, and mild acidosis. A liver biopsy showed diffuse accumulation of lipid droplets in swollen hepatocytes, and abnormal urinary metabolites included beta-hydroxy-beta-methyl glutarate (HMG), beta-methylglutaconate, beta-hydroxyisovalerate, and beta-methylglutaric and glutaric acids. In cultured skin fibroblasts and liver, beta-hydroxy-beta-methyl glutaryl CoA lyase activity was about 10% of normal. Therefore, a genetic deficiency of HMGCoA lyase activity can cause a clinical syndrome similar to that of Reye syndrome when the patient is stressed by an acute viral infection.
Asunto(s)
Hidroximetilglutaril-CoA Sintasa/deficiencia , Oxo-Ácido-Liasas/deficiencia , Síndrome de Reye/enzimología , Aminoácidos/sangre , Glucemia , Preescolar , Cromatografía por Intercambio Iónico , Humanos , Hidroxibutiratos/sangre , Lactatos/sangre , Hígado/patología , Masculino , Meglutol/orina , Síndrome de Reye/diagnósticoRESUMEN
The aim of this study was to assess the importance of low-density lipoprotein (LDL) particle size as a marker of atherogenic risk in male offspring of a parent with early coronary artery disease (CAD) before the age of 60 years. CAD-positive (CAD+) offspring were recruited into two groups based on age, 15 to 30 years (n = 20) and 31 to 45 years (n = 41), and matched to CAD-negative (CAD-) offspring by age and body mass index (BMI) (n = 20 and 21 per group). LDL peak particle diameter was assessed by polyacrylamide gradient gel electrophoresis. There was no significant difference in LDL peak particle diameter between CAD+ and CAD- offspring (26.2 +/- 0.1 v 26.2 +/- 0.1 nm, mean +/- SE). There was also no difference between CAD+ offspring and CAD- offspring when comparisons were made within their own age group (26.5 +/- 0.1 nm in younger CAD+ offspring v 26.2 +/- 0.1 nm in younger CAD- offspring, and 26.0 +/- 0.1 nm in older CAD+ offspring v 26.1 +/- 0.2 nm in older CAD- offspring). Peak particle diameter was significantly greater in younger CAD+ offspring than in older CAD+ offspring (26.5 +/- 0.1 v 26.0 +/- 0.1 nm, P < .05). We conclude that small LDL particle size is not a discriminating marker for early atherogenic risk, and that measurement of LDL particle size has limited value in the assessment of coronary risk, at least in the age ranges we studied.
Asunto(s)
Biomarcadores/química , Enfermedad Coronaria/etiología , Lipoproteínas LDL/química , Adolescente , Adulto , Factores de Edad , Estudios de Casos y Controles , Enfermedad Coronaria/genética , Electroforesis en Gel de Poliacrilamida , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
The relationship between low-density lipoprotein (LDL) peak particle diameter and insulin sensitivity, very-low-density lipoprotein (VLDL) + intermediate-density lipoprotein (LDL) triglyceride, cholesterol, and apoprotein B, postprandial lipemia, and LDL + high-density lipoprotein (HDL) triglyceride was assessed. The subjects were 101 healthy males aged 15 to 45 years. Sixty-one subjects (60.4%) were offspring of a parent with coronary artery disease before age 60, and 40 subjects (39.6%) had no parental history of coronary artery disease. LDL peak particle diameter was measured following polyacrylamide gradient gel electrophoresis. An insulin sensitivity index (Si) was determined from a frequently sampled intravenous glucose tolerance test using a minimal modeling method. A fat tolerance test was performed with a test meal containing 70 g/m2 fat, with triglyceride concentrations measured hourly for 12 hours. LDL peak particle diameter was significantly correlated with body mass index (BMI) (r = -.282, P < .01), waist to hip ratio (r = -.291, P < .01), fasting triglyceride (logarithmically [log] transformed) (r = -.566, P < .001), area under the postprandial triglyceride curve (log transformed) (r = -.562, P < .001), VLDL + IDL triglyceride (log transformed) (r = -.462, P < .001), VLDL + IDL cholesterol (log transformed) (r = -.477, P < .001), VLDL + IDL apoprotein B (log transformed) (r = -.321, P < .001), LDL + HDL triglyceride (log transformed) (r = .583, P < .001), and HDL cholesterol (r = .347, P < .001), but there was no significant correlation with Si. Using stepwise regression analysis, LDL + HDL triglyceride showed the strongest relationship to LDL peak particle diameter, accounting for 34% of the variation in size. Si was not an independent predictor of LDL particle size. In conclusion, insulin sensitivity appears to have little influence on LDL particle size. The importance of LDL + HDL triglyceride should be considered a preliminary finding warranting verification in this and other populations.
Asunto(s)
Resistencia a la Insulina/fisiología , Lipoproteínas LDL/química , Adolescente , Adulto , Ayuno/sangre , Humanos , Masculino , Persona de Mediana Edad , Tamaño de la Partícula , Análisis de Regresión , Triglicéridos/sangreRESUMEN
We investigated whether the male offspring of a parent with early coronary artery disease (before the age of 60; n = 61) exhibit decreased insulin sensitivity compared with controls matched for age and body mass index (BMI) (n = 39). The insulin sensitivity index (S[I]) was determined by the minimal modeling method of Bergman from a frequently sampled intravenous glucose tolerance test with intravenous tolbutamide. Offspring and controls had a similar S[I], insulin-independent glucose utilization (S[G]), first-phase insulin response (AIR[G]), and area under the glucose curve. When subjects were separated into two age groups, younger subjects aged 15 to 30 years and older subjects aged 31 to 45 years, important differences were seen. S[G] was significantly increased in younger offspring compared with controls (22.8 +/- 2.3 v 16.8 +/- 2.3 x 10(-3) x min(-1), P < .05). Older offspring had a significantly increased area under the glucose curve compared with controls (18,250 +/- 322 v 17,225 +/- 347 mg/dL x min(-1), P < .05). Older offspring also had decreased S[I] compared with younger offspring (5.0 +/- 0.4 v 6.6 +/- 0.9 x 10(-4) x min(-1) x micro U/mL, P < .05), but this difference was eliminated after adjusting for BMI and waist to hip ratio (5.5 +/- 0.4 v5.8 +/- 0.9 x 10(-3) x min(-1), nonsignificant). This study does not support the concept that insulin resistance is an early atherogenic risk factor in offspring at risk for coronary disease because of their family history. However, it does point to the importance of maturational changes in glucose homeostasis in these offspring.
Asunto(s)
Envejecimiento/fisiología , Enfermedad Coronaria/genética , Intolerancia a la Glucosa , Insulina/fisiología , Caracteres Sexuales , Adolescente , Adulto , Animales , Prueba de Tolerancia a la Glucosa , Cobayas , Humanos , Lipoproteínas/sangre , Masculino , Registros Médicos , Persona de Mediana Edad , Modelos Biológicos , Concentración Osmolar , Padres , Valores de ReferenciaRESUMEN
Rapid hormonal replacement of children with severe primary hypothyroidism frequently results in irritability and poor concentration. To alleviate these problems we have been using initial low-dose thyroxine treatment, building up to a final dose in an incremental manner over 4 1/2 to 6 months. Because of concern this regimen may compromise growth, we reviewed our experience treating 14 children and adolescents. For the 10 patients with remaining growth potential, 5 to 7 month growth velocity from the onset of treatment was 8.5 +/- 1.9 cm/year (range 5.7-10.9), and 5 to 7 month growth velocity z-score 1.5 +/- 1.7 (range 0.2-4.9). For the entire group, the thyroxine dose required to normalize TSH was 1.6 +/- 0.74 microgram/kg (range 0.9-3.4) or 60.7 +/- 18.9 micrograms/m2 (range 37.5-97.7). Based on the 5 to 7 month z-score, we conclude that satisfactory growth can be achieved on this regimen despite biochemical hypothyroidism. Thyroxine doses required to induce initial euthyroidism are lower than previously proposed.
Asunto(s)
Terapia de Reemplazo de Hormonas , Hipotiroidismo/tratamiento farmacológico , Tiroxina/uso terapéutico , Adolescente , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Estudios RetrospectivosAsunto(s)
Enfermedad de Graves/sangre , Hipotiroidismo/sangre , Complicaciones del Embarazo/sangre , Tirotropina/sangre , Tiroxina/sangre , Autoanticuerpos/sangre , Diagnóstico Diferencial , Femenino , Enfermedad de Graves/complicaciones , Humanos , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/etiología , Inmunoglobulinas Estimulantes de la Tiroides , Recién Nacido , Masculino , Intercambio Materno-Fetal , Tamizaje Neonatal , Embarazo , Pruebas de Función de la Tiroides , Tiroxina/administración & dosificación , Tiroxina/uso terapéutico , Proteínas de Unión a Tiroxina/químicaRESUMEN
OBJECTIVE: To provide an overview of the relationship between low-density lipoprotein (LDL) density and coronary artery disease and to examine this relationship in terms of lipid peroxidation and the atherogenic remnant hypothesis. DATA SOURCES: English-language studies and reviews pertaining to LDL composition and size were identified through a MEDLINE search and reference citations. STUDY SELECTION: Clinical studies on the following topics were critically reviewed: (1) the association between LDL density and coronary artery disease, (2) the relationship between LDL density and the levels and composition of other lipoproteins, and (3) the influence of environmental and genetic factors on LDL density. DATA SYNTHESIS: Low-density lipoprotein is a heterogeneous lipoprotein containing many subpopulations identifiable on the basis of density and size. There is an increased prevalence of small, dense LDL particles in coronary artery disease and conditions commonly associated with atherogenesis, such as non-insulin-dependent diabetes mellitus and familial combined hyperlipidemia. Exercise, visceral fat accumulation, and diet influence LDL density. In comparison with buoyant LDL, dense LDL is associated with a more atherogenic type of lipoprotein profile. An important relationship exists between the triglyceride level and the formation of LDL subpopulations. CONCLUSION: Unraveling the connection between dense LDL and atherogenesis should provide important insights into the basic mechanisms underlying atherogenesis.
Asunto(s)
Enfermedad de la Arteria Coronaria/etiología , Lipoproteínas LDL/química , Humanos , Lipoproteínas/sangre , Lipoproteínas LDL/clasificación , Lipoproteínas LDL/genética , Tamaño de la Partícula , Fenotipo , Triglicéridos/sangreRESUMEN
The prevalence of pediatric obesity is increasing in the United States. Sequelae from pediatric obesity are increasingly being seen, and long-term complications can be anticipated. Obesity is the most common cause of abnormal growth acceleration in childhood. Obesity in females is associated with an early onset of puberty and early menarche. Puberty is now occurring earlier in females than in the past, and this is probably related either directly or indirectly to the population increase in body weight. The effect of obesity on male pubertal maturation is more variable, and obesity can lead to both early and delayed puberty. Pubertal gynecomastia is a common problem in the obese male. Many of the complications of obesity seen in adults appear to be related to increased accumulation of visceral fat. It has been proposed that subcutaneous fat may be protective against the adverse effects of visceral fat. Males typically accumulate fat in the upper segment of the body, both subcutaneously and intraabdominally. In females, adiposity is usually subcutaneous and is found particularly over the thighs, although visceral fat deposition also occurs. Gender-related patterns of fat deposition become established during puberty and show significant familial associations. There are no reliable means for assessing childhood and adolescent visceral fat other than radiologically. Noninsulin-dependent diabetes is being seen more commonly in the pediatric population. Diabetes and impaired glucose tolerance are noted particularly in obese children with a family history of diabetes. In this situation, a glucose tolerance test may be indicated, even in the presence of fasting normoglycemia. Hypertriglyceridemia and low high-density lipoprotein-cholesterol levels are the primary lipid abnormalities of obesity and are related primarily to the amount of visceral fat. Low-density lipoprotein-cholesterol levels are not typically elevated in simple obesity. The offspring of parents with early coronary disease tend to be obese. Very low-density lipoprotein and intermediate-density lipoprotein particles, which are small in size, may be important in atherogenesis but they cannot be identified in a fasting lipid panel. The propensity to atherogenesis cannot be interpreted readily from a fasting lipid panel, which therefore should be interpreted in conjunction with a family history for coronary risk factors. Hypertriglyceridemia may be indicative of increased visceral fat, familial combined hyperlipidemia, familial dyslipidemic hypertension, impaired glucose tolerance, or diabetes. Almost half of adult females with polycystic ovary syndrome are obese and many have a central distribution of body fat. This condition frequently has its origins in adolescence. It is associated with increased androgen secretion, hirsutism, menstrual abnormalities, and infertility, although these may not be present in every case. Adults with polycystic ovary syndrome adults are hyperlipidemic, have a high incidence of impaired glucose tolerance and noninsulin-dependent diabetes, and are at increased risk for coronary artery disease. Weight reduction and lipid lowering therefore are an important part of therapy. Obstructive sleep apnea with daytime somnolence is a common problem in obese adults. Pediatric studies suggest that obstructive sleep apnea occurs in approximately 17% of obese children and adolescents. Sleep disorders in the obese may be a major cause of learning disability and school failure, although this remains to be confirmed. Symptoms suggestive of a sleep disorder include snoring, restlessness at night with difficulty breathing, arousals and sweating, nocturnal enuresis, and daytime somnolence. Questions to exclude obstructive sleep apnea should be part of the history of all obese children, particularly for the morbidly obese. For many children and adolescents with mild obesity, and particularly for females, one can speculate that obesity may not be a great health risk
Asunto(s)
Tejido Adiposo/metabolismo , Crecimiento/fisiología , Obesidad/complicaciones , Obesidad/metabolismo , Pubertad/fisiología , Adolescente , Adulto , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Niño , Diabetes Mellitus/etiología , Femenino , Humanos , Hipertrigliceridemia/etiología , Masculino , Obesidad/epidemiología , Síndrome del Ovario Poliquístico/etiología , Factores de Riesgo , Síndromes de la Apnea del Sueño/etiología , Tasa de SupervivenciaRESUMEN
Two infant boys developed scrotal hairs within the first three months of life. There was no other clinical or biochemical evidence of excessive androgen production, and no further progression of hair growth.
Asunto(s)
Cabello/crecimiento & desarrollo , Escroto , Humanos , Lactante , MasculinoRESUMEN
The association between diabetic ketoacidosis and acute pancreatitis is examined with reference to four patients. Hypertriglyceridemia was noted in only one of the patients. The pancreatitis was relatively mild and resolved rapidly.
Asunto(s)
Cetoacidosis Diabética/complicaciones , Pancreatitis/etiología , Enfermedad Aguda , Adolescente , Niño , Femenino , Humanos , Pancreatitis/diagnóstico , Pronóstico , Triglicéridos/sangreRESUMEN
A 12-year-old girl had a severe genu valgum deformity and osteomalacia with hypophosphatemia, hypercalciuria, and modestly elevated levels of 1,25-dihydroxyvitamin D3 and intact parathyroid hormone. This patient seems to have a different type of hypophosphatemic osteomalacia from that previously described.
Asunto(s)
Hipercalcemia/complicaciones , Hipercalcemia/orina , Hipofosfatemia/complicaciones , Osteomalacia/complicaciones , Calcitriol/administración & dosificación , Calcitriol/sangre , Calcitriol/uso terapéutico , Niño , Femenino , Humanos , Hipercalcemia/sangre , Rodilla/fisiopatología , Osteomalacia/tratamiento farmacológico , Osteomalacia/fisiopatología , Hormona Paratiroidea/sangre , Fósforo/uso terapéuticoRESUMEN
Increased chromosomal rearrangements and chromosomal fragility have been previously observed in lymphocytes of children treated with human GH, implying that treatment could predispose to malignancy. Twenty-four children with classic GH deficiency, neurosecretory GH dysfunction, and Turner syndrome were treated with recombinant human GH (0.3 mg x kg(-1) x wk(-1)). Metaphase cells were assessed for spontaneous chromosomal and chromatid aberrations at baseline and 6 mo into treatment. There were no significant differences in aberrations between baseline and the 6-mo samples. However, the mean frequency of chromatid-type aberrations on a per cell basis was significantly higher than at baseline, 0.0088 versus 0.0064 aberrations per cell (p < 0.024). Two patients contributed inordinately to this increase. A third sample from these two patients was almost identical to their baseline samples. Cells were also irradiated in vitro (3 Gy) to assess chromosomal fragility. After irradiation, no patient showed a significant difference for any aberration type, although there was a significantly lower frequency of ring chromosomes on a per cell basis in the 6-mo samples (p < 0.001). We find no evidence that GH therapy influences spontaneous chromosomal aberrations or chromosomal fragility.
Asunto(s)
Aberraciones Cromosómicas , Fragilidad Cromosómica , Trastornos del Crecimiento/tratamiento farmacológico , Hormona de Crecimiento Humana/efectos adversos , Linfocitos/efectos de los fármacos , Síndrome de Turner/tratamiento farmacológico , Adolescente , Células Cultivadas , Niño , Preescolar , Cromátides/efectos de los fármacos , Cromátides/efectos de la radiación , Cromosomas Humanos/efectos de los fármacos , Cromosomas Humanos/efectos de la radiación , Femenino , Trastornos del Crecimiento/sangre , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Linfocitos/sangre , Linfocitos/citología , Linfocitos/efectos de la radiación , Masculino , Metafase/efectos de los fármacos , Metafase/efectos de la radiación , Fase de Descanso del Ciclo Celular/efectos de la radiación , Síndrome de Turner/sangreRESUMEN
Gaucher disease is the most prevalent lysosomal storage disease. This autosomal recessive disease is caused by the defective activity of the enzyme acid beta-glucosidase and the resultant accumulation of glucosylceramide primarily within cells of the reticuloendothelial system. Because the primary manifestations of Gaucher disease are due to involvement of monocyte/macrophage-derived cells, this disease is thought to be an excellent candidate for curative intervention via bone marrow transplantation (BMT). A Hispanic female with subacute neuronopathic Gaucher disease and rapidly progressing visceral manifestations underwent BMT at 23 mo of age using her histocompatible normal brother as the donor. Cytogenetic analyses demonstrated complete, stable engraftment by 1 mo post-BMT. During the subsequent 24 mo, clinical, biochemical, enzymatic, and histologic studies demonstrated nearly complete correction in the viscera. Her neuropathic manifestations did not progress. Complete reconstitution of enzymatic activity in peripheral blood leukocytes was achieved by 1 mo. Cytogenetic analyses demonstrated complete engraftment by d 79 and nearly complete loss of bone marrow Gaucher cells was observed by 8 mo. Plasma glucosylceramide levels normalized by 8-12 mo. Nearly coincident improvements in hepatic size, enzyme levels, and histology were found by 12-24 mo post-BMT. Fatal sepsis occurred at 24 mo post-BMT. Autopsy revealed sparse Gaucher cells in clusters in the liver, lymph nodes, and lungs as well as the lack of periadventitial Gaucher cells surrounding brain vessels. The findings provide the time course and rationale for studies directed to gene therapy via BMT for this disease after introduction of acid beta-glucosidase gene constructs into autologous pluripotent stem cells of selected Gaucher disease patients.