July 2020 – Clinical Chemistry: Case 1

19 month old male was presented with frequent abdominal pains, constipation, sleep disorders, hyperactivity and high irritability. Upon evaluation, developmental delay for speech was also evident. Two of his older siblings, when younger had significant issues with attention deficit hyperactivity disorder (ADHD) but less severe than the patient.

What is the likely diagnosis?

  • Hepatotoxicity
  • Lactose intolerance
  • Acute intermittent Porphyria
  • Lead Toxicity

The correct answer is...

Correct answer is Lead Toxicity.

Lead poisoning often presents with the nonspecific signs and symptoms such as abdominal pain, constipation, irritability, and anemia with individual variations.

In the heme synthesis pathway, aminolevulinic acid dehydratase) is required for the conversion of aminolevulinic acid (sometimes denoted as ALA) to porphobilinogen and porphobilinogen deaminase helps in the conversion of porphobilinogen to porphyrins. Lead directly inhibits aminolevulinic acid dehydratase causing an impaired conversion of aminolevulinic acid to porphobilinogen. The result is an overproduction of aminolevulinic acid but normal levels of porphobilinogen. Acute intermittent porphyria is a rare autosomal dominant metabolic disorder caused from a deficiency of the porphobilinogen deaminase resulting in elevated levels of both aminolevulinic acid and porphobilinogen. Measurement of heme precursors in the urine such as aminolevulinic acid and porphobilinogen is crucial for the differential diagnosis between Lead poisoning and acute porphyria. In this case, since only the aminolevulinic acid and not the porphobilinogen were elevated, presence of acute porphyria was ruled out. One of the common and early clinical manifestations of lead poisoning includes irritability secondary to lead induced abdominal colic. Moreover, the patient’s abdominal pain was not specific to eating or drinking any dairy products, so the suspicion for lactose intolerance was eliminated. After exposure, most of the lead binds to the red blood cells and the rest is distributed to several organs such as liver, kidney and brain. Although causes for neurotoxicity is not clear, abnormal neural transmission due to oxidative stress and deregulated calcium signaling are some of the proposed mechanisms. Similar processes can also occur in the hepatic cells leading to its damage and release of transaminases into the blood stream.

Buildings with chipping and peeling lead paint and lead dust from these materials isthe most common sources of lead exposure in young children. The use of lead paint in construction was banned in 1978 in the United States. High levels of lead can cause permanent brain dysfunction, behavioral disorders, attention deficits and hyperactivity. The patient’s family lived in an older construction with damaged lead paint, which was later identified as the cause of lead poisoning. This had resulted in similar but less severe outcomes in the older siblings. The landlord was informed to recheck and correct the source of exposure by the Minnesota Department of Health.

1. T Venkatesh. Editorial role of a clinical biochemist in evaluating the impact of lead poisoning. Indian J Clin Bio chem. 2013;28(1):1–2.
2. JM Lamon. Clinical aspects of porphyrin measurement, other than lead poisoning. Clin Chem. 1977;23(2):260–63.
3. Castelbón Fernández FJ, Solares Fernandez I, Arranz Canales E, Enríquez de Salamanca Lorente R, Morales Conejo M. Protocol for Patients with Suspected Acute Porphyria. Rev Clin Esp. 2020; S0014-2565(20)30022-9.
4. Sanders, T., Liu, Y., Buchner, V., & Tchounwou, P. B. (2009). Neurotoxic effects and biomarkers of lead exposure: a review. Reviews on environmental health, 24(1), 15–45.
5. Protect Your Family from Sources of Lead - https://www.epa.gov/lead/protect-your-family-sources-lead.

Vijayalakshmi (Viji) Nandakumar, Ph.D., M.S.
Medical Director, Clinical Immunology, ARUP Laboratories
Assistant Professor of Pathology, University of Utah
Fellow, Clinical Chemistry, Mayo Clinic (2019-2020)

Photo of Joshua A. Bornhorst, Ph.D. Joshua Bornhorst, Ph.D.
Consultant, Clinical Biochemistry
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

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