Electrolyte homeostasis is maintained by the kidney through a complex transport function mostly performed by specialized proteins distributed along the renal tubules. Pathogenic variants in genes encoding these proteins impair this function and have consequences on the whole organism. Inherited tubulopathies represent a heterogeneous group of disorders characterized by impaired function of one or more of these specific transport molecules. The clinical consequences can range from isolated alterations in the concentration of specific solutes in blood or urine to serious and life-threatening disorders of homeostasis. Clinical manifestations of hereditary tubulopathies are commonly nonspecific and may include failure to thrive, stunted growth, poor feeding, recurrent vomiting, diarrhea, constipation, polyuria, polydipsia, or recurrent febrile episodes. In some instances, however, more specific manifestations such as rickets, urolithiasis, or hypertension aid in the diagnosis of a specific tubulopathy.
Kidney stone disease (or nephrolithiasis) is an increasingly prevalent condition with remarkable clinical heterogeneity, with regards to stone composition, age of manifestation, rate of recurrence, and impairment of kidney function. Calcium-containing kidney stones account for the vast majority of cases, but their etiology is poorly understood, notably their genetic drivers. Monogenic conditions are most likely underestimated in prevalence, and new disease genes are constantly being identified. Modes of inheritance in monogenic forms include autosomal-dominant, autosomal-recessive, and X-linked transmission. This panel includes sequence and deletion/duplication analysis of the listed genes.
