Unveiling atypical diagnoses: when whole-genome analysis performed for refractory infantile hypomagnesemia reveals primary hyperoxaluria

Genetic testing is increasingly recognized as crucial in inherited nephropathies. Here, we report on an atypical presentation of a complex tubulopathy that led to an unexpected diagnosis of primary hyperoxaluria type 1 (PH1).

At 2 weeks of age, a premature boy with stunted growth was diagnosed with complex tubulopathy associating hyponatremia, hypokalemia, hypomagnesemia, hypophosphatemia, metabolic acidosis, and acute kidney injury. Despite electrolyte replacement, severe hypomagnesemia persisted while massive parallel sequencing of genes involved in hypomagnesemia yielded negative results, including HNF1β. At 3 years of age, despite satisfactory growth, hypomagnesemia persisted and nephrocalcinosis appeared and progressed rapidly thereafter. Whole-genome analysis then revealed compound heterozygous mutations in the AGXT gene, thus leading to the diagnosis of PH1.

Given the emergence of new targeted therapies, thorough genetic analysis including whole-genome analysis should be pursued, especially in case of atypical clinical presentation.