Neurologic Sequelae of Lead Intoxication in a Child With Sickle Cell Disease

An 8-year-old female with sickle cell disease (SCD), hemoglobin SS genotype, global developmental delay, and pica established care shortly after moving from out of state. The patient and her family had been living in a weathered house. The child’s caregiver reported a recent history of weakness in the right side of her body, with preferential use of her non-dominant left hand, raising concerns for stroke. On physical examination, the child responded slowly to questions and had difficulty following complex commands. She demonstrated decreased strength of her right upper extremity; a slow, shuffling gait with both arms held in flexion and adduction; and reduced arm swing during walking. Her lifetime transcranial Doppler ultrasounds and recent magnetic resonance imaging and magnetic resonance angiogram of the brain were normal. Labs showed normal ranges of total iron, total iron binding capacity, and ferritin. Her exam findings, her history of pica without convincing evidence of iron deficiency, and her living situation raised our concerns for lead toxicity. Her blood lead level (BLL) was 44.8 mcg/dL. Shortly after this, she was admitted for initiation of chelation therapy with succimer.

During the past four decades, regulations have significantly reduced or eliminated lead content in household and industrial products, including paint and gasoline.¹ Because many of the effects of lead intoxication are irreversible, primary prevention has been a priority for regulatory agencies and children's advocacy groups. Even mildly elevated serum lead levels can cause variable degrees of cognitive impairment.¹ Higher levels may lead to behavioral problems, intellectual deficits, attention deficits, poor growth, hearing impairment, and kidney damage.¹

Anemia in lead poisoning results from inhibition of ferrochelatase and delta-aminolevulinic acid dehydratase, which is involved in synthesizing heme.² A cross-sectional study by Leah Seifu, MD, MPH, and colleagues reported a potential association between SCD and increased lead levels.³ In this New York-based study, data from 2005 to 2019 showed that SCD was found among 2.14% of black children with BLLs of 15 mcg/dL or greater. Notably, peak BLL (42.59 vs. 23.06 mcg/dL; p=.008), as well as the mean age at peak BLL (62.8 vs 42.7 months; p=.003) were higher among patients with SCD than in children without SCD.³ Children with SCD were significantly more likely to engage in both pica and chewing non-food items compared to those without SCD — behaviors that can also be seen in iron deficiency.³ Importantly, iron deficiency is an independent risk factor for lead poisoning due to the upregulation of intestinal iron transporters that facilitate the absorption of other divalent metals such as manganese, lead, and cadmium.⁴ Of note, although this study highlights the importance of lead poison prevalence in SCD, many confounding factors could have affected the outcomes, including the difference in the proportion of children who lived in older homes among both cohorts (97% in the SCD cohort vs. 88% in the non-SCD cohort), as well as unexplored environmental factors.

Lead poisoning in patients with SCD can be challenging to diagnose due to overlapping symptom profiles.⁵ SCD is associated with cognitive delays, as well as silent or overt strokes. Chronic lead poisoning can lead to similar symptoms and must remain on the differential when faced with neurologic dysfunction and cognitive challenges that could be misattributed to SCD. Establishing chronicity and characterizing these symptoms in detail is essential to avoiding misdiagnosis and delays in care.

1. Council on Environmental Health, Lanphear BP, Lowry JA, et al. Prevention of childhood lead toxicity. Pediatrics. 2016;138(1):e20161493.
2. Balali-Mood M, Naseri K, Tahergorabi Z, et al. Toxic mechanisms of five heavy metals: mercury, lead, chromium, cadmium, and arsenic. Front Pharmacol. 2021;12:643972.
3. Seifu L, Sedlar S, Grant T, et al. Sickle cell disease and lead poisoning in New York City, 2005–2019. Pediatrics. 2024;154(Suppl 2):e2024067808G.
4. Kim Y, Park S. Iron deficiency increases blood concentrations of neurotoxic metals in children. Korean J Pediatr. 2014;57(8):345-350.
5. Jung JM, Peddinti R. Lead toxicity in the pediatric patient with sickle cell disease: unique risks and management. Pediatr Ann. 2018;47(1):e36-e40.

Disclosure Statement: The authors indicated no relevant conflicts of interest.

Acknowledgment: This article was reviewed by Damilola Akani, MD, MPH, and Alexander Boucher, MD.