Lead and δ-Aminolevulinic Acid Dehydratase Polymorphism: Where Does It Lead? A Meta-Analysis

BACKGROUND: Lead poisoning affects many organs in the body. Lead inhibits δ-aminolevulinic acid dehydratase (ALAD), an enzyme with two co-dominantly expressed alleles, ALAD1 and ALAD2. OBJECTIVE: Our meta-analysis studied the effects of the ALAD polymorphism on a) blood and bone lead levels and b) indicators of target organ toxicity. DATA SOURCE: We included studies reporting one or more of the following by individuals with genotypes ALAD1-1 and ALAD1-2/2-2: blood lead level (BLL), tibia or trabecular lead level, zinc protoporphyrin (ZPP), hemoglobin, serum creatinine, blood urea nitrogen (BUN), dimercaptosuccinic acid–chelatable lead, or blood pressure. DATA EXTRACTION: Sample sizes, means, and standard deviations were extracted for the genotype groups. DATA SYNTHESIS: There was a statistically significant association between ALAD2 carriers and higher BLL in lead-exposed workers (weighted mean differences of 1.93 μg/dL). There was no association with ALAD carrier status among environmentally exposed adults with BLLs < 10 μg/dL. ALAD2 carriers were potentially protected against adverse hemapoietic effects (ZPP and hemoglobin levels), perhaps because of decreased lead bioavailability to heme pathway enzymes. CONCLUSION: Carriers of the ALAD2 allele had higher BLLs than those who were ALAD1 homozygous and higher hemoglobin and lower ZPP, and the latter seems to be inversely related to BLL. Effects on other organs were not well delineated, partly because of the small number of subjects studied and potential modifications caused by other proteins in target tissues or by other polymorphic genes

A Coordinated Relocation Strategy for Enhancing Case Management of Lead Poisoned Children: Outcomes and Costs

Controlling residential lead hazards is critical for case management of lead poisoned children. To attain this goal, permanent relocation of the family is sometimes necessary or advisable for many reasons, including poor housing conditions; extensive lead hazards; lack of abatement resources, landlord compliance and local enforcement capacity; and family eviction. During 1996–1998, the Kennedy Krieger Institute implemented a unique capitated program for case management of Baltimore City children with blood lead concentrations (PbB) >19 μg/dL. The Program provided financial, housing, and social work assistance to facilitate relocation as a means of providing safer housing. Nearly half of the Program families relocated with direct assistance, and 28% relocated on their own. The Program evaluation examined the costs and benefits of relocation. Average relocation cost per child was relatively inexpensive (<$1,500). Average relocation time of 5 months (range <2 months to >12 months) was less than the 8-month average time to complete lead hazard control work in 14 city and state programs funded by U.S. HUD. Relocation was associated with (1) a statistically significant decrease in dust lead loadings on floors, windowsills and window troughs that persisted for one year, and (2) statistically significantly greater decreases in children’s PbB compared to children who did not relocate from untreated homes. Children relocated to housing that met current Federal residential dust lead standards had statistically significant decreases in blood lead levels. Visual inspection did not consistently identify relocation houses with dust lead levels below current Federal standards, indicating that dust testing should be an essential component of future programs. This will require additional resources for dust testing and possibly cleaning and repairs but is expected to yield additional benefits for children. The findings support recent U.S. CDC case management recommendations suggesting that permanent relocation to safer housing is a viable means to reduce children’s lead exposure. The benefits of relocation notwithstanding, 40% of families moved at least twice. Research is needed to better understand how to expedite relocation and encourage families to remain in safe housing. Relocation does not negate owners’ and health authorities' responsibilities to address lead hazards in the child's original house in order to protect future occupants