Body composition in prepubertal children with human immunodeficiency virus type 1 infection.

OBJECTIVE: To characterize the body composition of human immunodeficiency virus (HIV)-infected children, especially those with growth failure (GF), using laboratory-based methods. DESIGN: A cross-sectional study of body composition measurements. SETTING: Urban, hospital-based body composition laboratory. PARTICIPANTS: Thirty-four prepubertal children with HIV infection, aged 4 to 11 years, recruited from a pediatric HIV clinic. Eighteen HIV-infected children with GF, 16 HIV-infected children with normal rates of growth, and 52 healthy children were studied. MAIN OUTCOME MEASUREMENTS: Anthropometrics, body cell mass (BCM) by total body potassium counting, body fat percent, fat mass, and fat-free mass (FFM) by dual-energy x-ray absorptiometry were determined. RESULTS: Both groups of boys with HIV infection had significantly lower FFM/height ratios compared with healthy boys. The mean BCM/height ratio was also lower in HIV-infected boys with GF compared with healthy boys. Measures of fat of the HIV-infected boys with GF did not differ from healthy controls, but a statistical trend suggesting decreased body fat percent and fat mass/height ratio was observed in HIV-infected boys without GF (P=.06 and .07, respectively). Mean height-for-age, weight-for-age, and weight-for-height percentiles were significantly decreased in HIV-infected boys regardless of growth status as compared with healthy boys. The mean FFM/ height and BCM/height ratios were decreased in HIV-infected girls with GF compared with healthy girls. Body fat percentage and fat mass/height ratio did not differ among the 3 groups of girls. The mean weight-for-height percentiles were not different among the 3 groups of girls. The HIV-infected girls with GF had significantly lower mean height-for-age and weight-for-age percentiles than HIV-infected girls without GF and healthy girls. The mean height-for-age percentiles of the HIV-infected girls with GF did not differ from the healthy girls. CONCLUSIONS: Boys and girls with HIV-associated GF had diminished FFM and BCM. The decrease in FFM and BCM was in striking contrast to the fat compartment, which was normal. Decreased FFM was also detected in boys with HIV infection and normal growth but not in girls with HIV infection and normal growth, suggesting that HIV infection may affect boys differently than girls. The preferential decrease in FFM and BCM over fat observed in these children is similar to findings reported in adults with acquired immunodeficiency syndrome wasting.

Diagnosis of X-linked adrenal hypoplasia congenita by mutation analysis of the DAX1 gene.

OBJECTIVE: To develop a rapid diagnostic approach to individuals with the X-linked cytomegalic form of adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH) due to mutations in DAX1, a new member of the nuclear hormone receptor gene superfamily. DESIGN: Molecular genetic diagnostic investigations of individuals with AHC and their relatives included polymerase chain reaction amplification of DAX1 for identification of intragenic mutations and fluorescence in situ hybridization with a cosmid containing the DAX1 gene for evaluation of larger deletions. PARTICIPANTS: Families that had males affected with AHC were evaluated for mutations involving the DAX1 gene. RESULTS: DAX1 mutations were identified in four families that had males affected with AHC. Two apparently independent pedigrees had an identical frame-shift mutation due to a single base pair deletion, and a third had a larger deletion involving the entire DAX1 locus. The fourth family was evaluated by fluorescence in situ hybridization for prenatal diagnosis, and both the DAX1 locus and the contiguous glycerol kinase region were deleted. CONCLUSIONS: Molecular genetic and molecular cytogenetic techniques represent rapid and complementary approaches to the diagnosis of mutations in the DAX1 gene responsible for AHC and the associated HH. Specific diagnosis of the cause of adrenal insufficiency in these boys permits anticipatory management of the HH and prenatal counseling for parents of the affected child and other members of their families.

Familial Pallister-Hall syndrome: case report and hormonal evaluation.

Pallister-Hall syndrome is a usually lethal dysplasia/malformation syndrome characterized by hypothalamic hamartoblastoma, hypopituitarism, postaxial polydactyly, craniofacial malformations, imperforate anus, and other malformations. We report a familial case in a male infant and his female sib fetus, suggesting autosomal recessive inheritance, or germinal mosaicism for an autosomal dominant mutation, or a segregating submicroscopic chromosome abnormality. Detailed endocrine evaluation on the surviving infant revealed documented pituitary function, pituitary deficit, and hypothalamic deficiency. We suggest that hypothalamic dysfunction contributes to the hypopituitarism seen in Pallister-Hall syndrome.

Inappropriate suppression of thyrotropin during medical treatment of Graves disease in childhood.

Twenty-nine patients (22 female) aged 2 to 17 years were followed with serial measurements of serum triiodothyronine, thyroxine, and thyrotropin during medical therapy for Graves disease. Fourteen patients had 17 instances of hypothalamic-pituitary-thyroid suppression with inappropriately low thyrotropin levels. Five patients had six episodes of low thyroxine and triiodothyronine levels with normal levels of thyrotropin, and 10 patients had 11 episodes of normal thyroxine and triiodothyronine levels with subnormal levels of thyrotropin. We conclude that thyrotropin values may not be reliable for diagnosing either mild hypothyroidism or persistent hyperthyroidism during the medical treatment of Graves disease.

46,XX pure gonadal dysgenesis with growth hormone deficiency and impaired 3 beta-hydroxysteroid dehydrogenase activity.

Patients with 46,XX pure gonadal dysgenesis generally are of normal stature and have less than usual amounts of pubic and axillary hair. We report on a patient who presented at age 11.9 years with short stature, absence of breast development, and excessive pubic hair. Her karyotype in leukocytes, fibroblasts, and streak gonad was 46,XX. The patient was diagnosed as having growth hormone deficiency. Elevated ACTH stimulated levels of 17-hydroxypregnenolone and dehydroepiandrosterone and elevated ACTH stimulated ratio of 17-hydroxypregnenolone to 17-hydroxyprogesterone suggested inadequate adrenal 3 beta-hydroxysteroid dehydrogenase activity. Treatment with growth hormone resulted in improvement in growth velocity and replacement with estrogen in feminization. We suggest that the finding of short stature in patients with 46,XX pure gonadal dysgenesis should not be attributed to the syndrome, but rather requires investigation for possible growth hormone deficiency. The poor growth of our patient prior to growth hormone replacement implies that dehydroepiandrosterone, unlike testosterone and estrogen, is ineffective in promoting linear growth in the absence of adequate growth hormone.

Very low-density lipoprotein metabolism in an unusual case of lipoatrophic diabetes.

Complete acquired lipoatrophic diabetes (LD) is characterized by nonketotic insulin-resistant diabetes, elevated very low-density lipoprotein (VLDL) triglyceride (TG) levels, and absent subcutaneous fat. We studied a young child in whom LD atypically developed after the onset of type 1 diabetes mellitus. On uncontrolled home diet the patient had triglyceride levels over 1,000 mg/dL on multiple occasions. In order to demonstrate the effects of caloric and dietary-fat restriction on VLDL metabolism, 3H-glycerol and autologous 125I-VLDL were used to quantitate the turnover of VLDL-TG and VLDL-apolipoprotein B (apo B) during two periods of caloric restriction. Consumption of a 900-kcal 40-g fat diet resulted in a plasma triglyceride level of 1383 mg/dL (ten-fold elevation). This hypertriglyceridemia was associated with markedly increased production rates of both VLDL-TG (73.7 mg/kg/h) and VLDL-apo B (126.9 mg/kg/d). Consumption of a 900-kcal 25-g fat diet resulted in a plasma TG level of 663 mg/dL. This reduction in plasma TG was associated with a 40% decrease in VLDL-TG production rate (PR) (45.1 mg/kg/h). There was no change in the production rate (PR) of VLDL-apo B. The hypertriglyceridemia in this patient was due to marked over production of VLDL. Furthermore, the studies demonstrate: (1) the independent benefits of caloric and dietary-fat restriction in the treatment of LD, and (2) that fat restriction lowered plasma triglyceride by its effect on the VLDL-TG production rate.