Search

Focal dermal hypoplasia (FDH) is a rare genetic disorder caused by mutations in the PORCN gene located on the X chromosome. Short stature was previously noted to be a common finding in FDH, however the etiology of this is unclear. The present study sought to elucidate specific causes for short stature by assessing growth charts, determining bone ages and auxologic measurements, examining laboratory data for the common causes of growth failure, assessing dietary intake, and performing a growth hormone stimulation test. Sixteen patients with FDH between the ages of 3 and 18 years of age consented to the study. While 11 out of 16 patients had short stature based on height less than 2 standard deviations below mid-parental target height percentile and bone age not suggestive of likely catch-up growth, only four had a BMI less than the 5th percentile for age. Laboratory studies did not support a gastrointestinal, allergy or autoimmune cause of growth failure. Three patients had results suggestive of possible growth hormone deficiency. Although short stature is a common feature in FDH, our data suggests that severe undernutrition is not common in this group and that there may be underlying treatable causes for this short stature in some patients.

Background: HIV infection occurs in 30% of children with severe acute malnutrition in sub-Saharan Africa. Effects of HIV on the pathophysiology and recovery from malnutrition are poorly understood. Methods: We conducted a prospective cohort study of 75 severely malnourished Ugandan children. HIV status/CD4 counts were assessed at baseline; auxologic data and blood samples were obtained at admission and after 14 days of inpatient treatment. We utilized metabolomic profiling to characterize effects of HIV infection on metabolic status and subsequent responses to nutritional therapy. Findings: At admission, patients (mean age 16.3 mo) had growth failure (mean W/H z-score 24.27 in non-edematous patients) that improved with formula feeding (mean increase 1.00). 24% (18/75) were HIV-infected. Nine children died within the first 14 days of hospitalization; mortality was higher for HIV-infected patients (33% v. 5%, OR=8.83). HIV-infected and HIV-negative children presented with elevated NEFA, ketones, and even-numbered acylcarnitines and reductions in albumin and amino acids. Leptin, adiponectin, insulin, and IGF-1 levels were low while growth hormone, cortisol, and ghrelin levels were high. At baseline, HIV-infected patients had higher triglycerides, ketones, and even-chain acylcarnitines and lower leptin and adiponectin levels than HIV-negative patients. Leptin levels rose in all patients following nutritional intervention, but adiponectin levels remained depressed in HIV-infected children. Baseline hypoleptinemia and hypoadiponectinemia were associated with increased mortality. Conclusions: Our findings suggest a critical interplay between HIV infection and adipose tissue storage and function in the adaptation to malnutrition. Hypoleptinemia and hypoadiponectinemia may contribute to high mortality rates among malnourished, HIV-infected children.

Malnutrition is a major cause of childhood morbidity and mortality. To identify and target those at highest risk, there is a critical need to characterize biomarkers that predict complications prior to and during treatment.We used targeted and nontargeted metabolomic analysis to characterize changes in a broad array of hormones, cytokines, growth factors, and metabolites during treatment of severe childhood malnutrition. Children aged 6 months to 5 years were studied at presentation to Mulago Hospital and during inpatient therapy with milk-based formulas and outpatient supplementation with ready-to-use food. We assessed the relationship between baseline hormone and metabolite levels and subsequent mortality.Seventy-seven patients were enrolled in the study; a subset was followed up from inpatient treatment to the outpatient clinic. Inpatient and outpatient therapies increased weight/height z scores and induced striking changes in the levels of fatty acids, amino acids, acylcarnitines, inflammatory cytokines, and various hormones including leptin, insulin, GH, ghrelin, cortisol, IGF-I, glucagon-like peptide-1, and peptide YY. A total of 12.2% of the patients died during hospitalization; the major biochemical factor predicting mortality was a low level of leptin (P = .0002), a marker of adipose tissue reserve and a critical modulator of immune function.We have used metabolomic analysis to provide a comprehensive hormonal and metabolic profile of severely malnourished children at presentation and during nutritional rehabilitation. Our findings suggest that fatty acid metabolism plays a central role in the adaptation to acute malnutrition and that low levels of the adipose tissue hormone leptin associate with, and may predict, mortality prior to and during treatment.

Among the factors predisposing to type 2 diabetes in children, adolescents, and young adults, the health and behavior of both the mother and father are critical. Prevention and treatment of parental nutritional disorders (including obesity and malnutrition), promotion of breastfeeding, and avoidance of overfeeding of young children are essential for childhood health and metabolic function. Focusing research and policy on parental influences on childhood health should reduce the risks of obesity and type 2 diabetes in future generations.