Bone Abstracts

Background: 3 year old boy born to non-consanguineous parents. He was diagnosed to have autism at 2 years of age. He had a history of pica.

Presenting problem: He was admitted with severe carpopedal spasms of hands and feet. Investigations revealed severe hypomagnesaemia at 0.26 (0.7–1.0) mmol/l, hypocalcaemia at 1.59 (2.2–2.6) mmol/l, hypokalaemia, hyponatremia and moderately low vitamin D levels. Parathyroid hormone concentration was low. Urine analysis revealed loss of sodium, calcium, magnesium and sodium. Renal functions and renal ultrasound were normal.

Clinical management: He received multiple intravenous infusions of sodium, potassium, calcium and magnesium and was started on oral calcium, magnesium and colecalciferol. Hypocalcaemia resolved within few days. Parathyroid hormone concentrations normalised on treatment with intravenous magnesium. However, hypomagnesaemia was severe and persistent despite treatment and renal magnesium losses continued.

Meanwhile, blood film analysis revealed basophilic stippling of red blood cells suggestive of lead poisoning. Plasma lead concentration was extremely high and he received chelation therapy with dimercaptosuccinic acid, following which lead concentrations decreased. During chelation treatment, intravenous magnesium was switched to oral magnesium which could be gradually weaned and stopped after 10 weeks.

Genetic studies sent to assess known genetic causes of hypomagnesaemia revealed a previously described, but heterozygous mutation in CLDN16 gene. Heterozygous carriers are not usually symptomatic.

Discussion: Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive condition that is caused by homozygous mutations in the CLDN16 gene, which encodes claudin-16, an important tight junction protein expressed in Henle’s loop and distal tubule of the kidney. FHHNC is characterised by excessive renal magnesium and calcium loss, persistent hypomagnesaemia, nephrocalcinosis and renal failure. The overall prognosis is poor, and definitive cure is by renal transplantation.

It is known that lead poisoning causes toxic effects to all organs, including the kidney, although magnesium loss has not been previously described in humans. In young rats, competitive antagonism between lead, calcium and magnesium has been shown in experimental studies. We suggest that, in our patient, lead poisoning resulted in hypermagnesuria in the context of a heterozygous CLDN16 mutation.

Disclosure: The authors declared no competing interests.