Hypophosphatemic Rickets as a Key Sign for the Diagnosis of Hereditary Tyrosinemia Type 1: Case Reports and Narrative Review of the Literature.

Hereditary tyrosinemia type 1 (HT-1) is an inborn error of metabolism caused by a defect in tyrosine (tyr) degradation. This defect results in the accumulation of succinylacetone (SA), causing liver failure with a high risk of hepatocarcinoma and kidney injury, leading in turn to Fanconi syndrome with urine loss of phosphate and secondary hypophosphatemic rickets (HR). HT-1 diagnosis is usually made in infants with acute or chronic liver failure or by neonatal screening programs. HR is rarely described in the literature as the main feature or chief complaint of patients with HT-1. Clinical cases: We present three children who presented signs of HR during infancy. Patient 1 had early liver dysfunction, leading to a quick diagnosis of HT-1. Patients 2 and 3 started conventional therapy for HR (calcitriol and oral phosphate) with partial clinical response. Later, both developed liver dysfunction, and patient 3 presented neurological symptoms (porphyria-like crises). An HT-1 diagnosis was made using tandem mass spectrometry, which confirmed high plasma levels of SA and tyr. After diagnosis, all started treatment with a specific diet and nitisinone with prompt recovery and a quick remission of clinical signs of HR, being able to discontinue their conventional rickets therapy successfully.

Conclusion

We present three patients with HT-1 whose main complaint was HR. It is important to know the main features of this metabolic disorder and have a high index of suspicion when we follow-up children with HR, especially if they are not responding to conventional therapy or develop liver dysfunction.