A case of nephrocalcinosis in a 7‐month‐old with congenital hypothyroidism: Insights from targeted exome sequencing

Abstract

Abstract Nephrocalcinosis is a complex disease with a multitude of triggering factors. An association with congenital hypothyroidism has been described in the literature, but the mechanisms leading to its development remain unclear. A 7‐month‐old infant presented with muscular hypotonia and signs of malnutrition was diagnosed with congenital hypothyroidism, nephrocalcinosis of unclear origin, and multiple kidney stones. Urine analysis revealed the presence of calcium oxalate crystals and slightly elevated oxaluria without hypercalciuria. Targeted exome sequencing found no variants in the four causative genes of primary oxaluria, namely AGXT, CBX5, GRHPR, and HOGA1. The clinical outcome was favorable with thyroid hormone and potassium citrate treatment. Ultrasound follow‐up showed progressive improvement of nephrocalcinosis. The low level of urinary oxalate and the prevalence of dihydrate calcium oxalate crystals spoke against primary or secondary oxaluria. Recent evidence from mitochondrial research shows that thyroid hormone T3 enhances mitochondrial calcium levels by stimulating calcium uptake by the mitochondrial calcium uniporter. A reduced calcium uptake and metabolism in mitochondria might represent an explanation for cytoplasmic calcium accumulation in tubular cells, subsequently precipitating nephrocalcinosis in the absence of thyroid hormone. Even if the pathophysiological mechanisms are not yet fully understood, recent evidence is supportive of a causal relationship between hypothyroidism and nephrocalcinosis, a sometimes overlooked association.

Keywords

• congenital hypothyroidism
• hyperoxaluria
• nephrocalcinosis
• targeted exome sequencing