...but thou shalt conceive and bear a son. Now therefore beware, I pray thee, and drink not wine nor strong drink...
- Judges 13:3-4

Poisonous substances either biological or chemical that cause injury or death. Most important in the pediatric population are: lead, mercury, and alcohol.

Lead: plumbism (inorganic lead)
Mercury: erethism, mad hatter's disease, Minamata disease, pink disease
Alcohol: fetal alcohol syndrome

Epidemiology

Lead
• documented cases of lead poisoning are very rare
• intoxication with inorganic lead was previously common, organic lead from tetraethyl lead (gasoline)
• current source of inorganic lead is ingestion of paint chips or inhalation of contaminated dust in old buildings
• recent sources of organic lead is inhalation of gasoline
Mercury
• organic form more common in intoxication
• inorganic form in industrial workers
• ?inorganic form from maternal-fetal transfer of amalgam?
• organic intoxication usually from specific locales - Japan (Minamata, ingestion of contaminated fish) and Iraq (ingestion of bread made from wheat that was sprayed with mercury-containing antifungal)
Alcohol
• most common intoxicant from maternal-fetal transfer
• FAS incidence of 1-2 live births per 1000
• likely affects 1% of babies whose mothers drink 1oz. EtOH daily
• affects 30% babies whose mothers drink heavily

Risk Factors

Lead
• pica in children in old deteriorating buildings
• low calcium in diet enhances the absorption of lead
Mercury
• environmental contamination of food sources
Alcohol
• maternal alcohol consumption
• toddler gaining access to alcohol at home
All three toxins cross placental and damage the fetus
Suggested that maternal genotype may be factor in elimination rate for alcohol and thus susceptibility to fetal exposure

Clinical Features

Lead
• overt or subclinical encephalopathy
• pale, irrtable, listeless, anorexia
• epigastric pain, vomiting, constipation
• convultions, decreased LOC
• can develop hemiplegia, symptoms of increased ICP with nucchal rigidity
• some children can be ataxic or have CN 6-7 palsies
• peripheral neuropathy legs > arms, e.g., footdrop
• anemia with basophilic stippling of RBCs, abnormal renal tubular function and renal rickets
• elevated cell count and protein in CSF
• X-rays show opacities in long bone metaphyses
• tests include microcytic anemia, basophilic stipling, alpha-aminolevulinic acid dehydratase, zinc protoporphyrin, blood/urine levesl of coproporphyrin III and free erythrocyte protoporphyrin
Mercury
• inorganic mercury: ataxia, dysarthria, bilateral concentric constriction of visual fields, impaired hearing, sensory disturbance, tremor, muscle weakness, abnormal eye movements, dysequilibrium, chorea, ballismus, convulsions, athetosis, crying, mental disorder
Fetal alcohol syndrome (FAS)
• wide spectrum of abnormalities
• mental retardation, micrencephaly, hypotonia, poor coordination, hyperactivity
• growth deficiency and distinctive facies
• facial abnormalities: short palpebral fissures, short upturned nose, hypoplastic philtrum, hypoplastic maxilla, thin vermilion lip border, retrognathia (infancy)/micrognathia/prognathia (adolescence)
• less common abnormalities in musculoskeletal system, skin, urogenital tract, and cardiovascular system

Macroscopy

Lead
• severe brain swelling with or without congestion and petechial hemorrhages
• gross changes may be absent in lethal cases
Mercury
• features depend on age of exposure
• In utero - global necrosis and decreased brain weight
• Adult exposure - less atrophy
• Leptomeninges fibrotic, especially in occipital lobes
• brain swelling in acute/subacute intoxication
• cystic destruction/sclerosis of parenchyma
• Cerebral and cerebellar cortex preferentially affected, especially vermian folia
FAS
• microcephaly, agenesis of corpus callosum, hydrocephaus, cerebellar abnormalities, microphthalmia
• holoprosencephaly and septo-optic dysplasia have been observed

Histopathology

Lead
• no pathognomonic microscopic changes
• vascular - diliation of small vessels with endothelial swelling
• occasional thrombosis and leaking of serum into tissues
• petechial hemorrhages, especially in the cerebellum
• Astrocytosis, necrosis
• affects both Purkinje cells and granular cells
• intranuclear inclusion bodies o flead in some organs, e.g., kidney and liver
Mercury
• in utero exposure:
  • global cerebral neuronal necrosis
  • disorganization of cellular architecture
  • hypoplasia of the corpus callosum
  • hypoplasia of the cerebellar granule cell layer
• postnatal/adult exposure:
  • severe destruction of cerebellar granule cells
  • cortical neuronal damage, esp. occipital
  • displacement of Purkinje cells and torpedoes
  • stellate bodies in the molecular layer, or cactus formation
  • dendritic abnormalities of the Purkinje cells
  
• demonstration of mercury deposits witih histochemistry
FAS
• heterotopias and dysplasias
• spongy state of thalamus/hypothalamus

Differential Diagnosis

Lead
• infection, trauma, metabolic disorders, CNS hemorrhage, CNS tumour
• diganosis by toxicological analysis
Mercury
• congenital granular cell atrophy is the only other differential in selective destruction of cerebellar granular cells
FAS
• findings are nonspecific, including similarities to a number of genetic disorders

Pathogenesis

Lead
• mechanism unclear
• may be related to changes in second messenger systems involving calcium
Mercury
• methylated and demethylated mercury interacts with sulfhydryl ligands in membranes or enzyme complexes
• calcium homeostasis, neurotrasmitter metabolism, membrane biophysical properties, mitotic potential, and energy potential are disturbed
FAS
• mechanism unclear
• may be due to:
  • hypoxia from umbilical vasospasm
  • membrane damage from lipid peroxidation
  • acetaldehyde toxicity
  • inhibition of nerve growth factors
  • chromosomal damage