Tubulopathy


Tubulopathy is a disease affecting the renal tubules of the nephron.
Tubulopathic processes may be inflammatory or noninflammatory, though inflammatory processes are often referred to specifically as tubulitis.
Disorder Protein DefectChromosome LocalizationInheritanceClinical Features/NotesBiochemical Features-
Proximal Tubule-
Lowe's syndrome CLCN5Xp11.22XRNephrocalcinosis, nephrolithiasis, rachitic and osteomalacic bone disease, progressive kidney failure, normotensivePlasma: ↓PO4, N/↓K; Urine: ↑LMWP, ↑AA, ↑K, ↑Ca, ↑PO4, ↑Glycosuria-
X-linked dominant hypophosphatemic rickets ROMK 11q24ARPolyuria, polydipsia, muscle weakness, hypovolemia, normotensive or hypotensive. Maternal polyhydramnios, premature birth, perinatal salt wasting, nephrocalcinosis and kidney stones, milder phenotype with normocalciuria, sensorineural deafness, motor retardation, renal failure
C1C-Kb 1p36ARPolyuria, polydipsia, muscle weakness, hypovolemia, normotensive or hypotensive. Maternal polyhydramnios, premature birth, perinatal salt wasting, nephrocalcinosis and kidney stones, milder phenotype with normocalciuria, sensorineural deafness, motor retardation, renal failure
1p31ARPolyuria, polydipsia, muscle weakness, hypovolemia, normotensive or hypotensive. Maternal polyhydramnios, premature birth, perinatal salt wasting, nephrocalcinosis and kidney stones, milder phenotype with normocalciuria, sensorineural deafness, motor retardation, renal failure
Barttin Polyuria, polydipsia, muscle weakness, hypovolemia, normotensive or hypotensive. Maternal polyhydramnios, premature birth, perinatal salt wasting, nephrocalcinosis and kidney stones, milder phenotype with normocalciuria, sensorineural deafness, motor retardation, renal failure
Hypomagnesemic hypercalciuric nephrocalcinosis PCLN13q27ARNephrocalcinosis, renal failure, ocular/hearing defects, polyruria, polydipsia, recurrent urinary tract infections, recurrent renal colic, normotensivePlasma: ↓Mg, ↑PTH; Urine: ↑Ca, ↑Mg-
Distal Tubule/Collecting Duct-
Liddle's syndrome ENaC 16p13-p12ADEarly, and frequently severe, hypertension, strokePlasma: ↓renin, ↓K, ↓Mg, ↑CO2; Urine: ↑K-
Pseudohypoaldosteronism type 1a ENaC 12p13, 16p13-p12ARPresents in infancy with salt-wasting and hypotension, Cough, respiratory infectionsPlasma: ↑renin, ↓Na, ↑K, ↓CO2; Urine: ↑K-
Pseudohypoaldosteronism type 1b Mineralocorticoid receptor4q31.1ADPresents in infancy with salt-wasting and hypotension. Milder than type 1a and remits with agePlasma: ↑renin, ↓Na, ↑K, ↓CO2; Urine: ↑K-
Pseudohypoaldosteronism type 2 Unknown 1q31-q42, 12p13, 17q21-q22ADHypertension. Correction of physiologic abnormalities by thiazide diureticsPlasma: ↓renin, ↑K, ↓CO2, ↑Cl; Urine: ↓K-
Gitelman's syndrome NCCT16q13ARHypotension, weakness, paresthesias, tetany, fatigue, and salt craving, Presentation generally much later in life than in Bartter's and hypocalciuria is typicalPlasma: ↑renin, ↓K, ↓Mg, ↑CO2; Urine: ↓calcium:creatinine excretion ratio -
X-linked nephrogenic diabetes insipidus type 1 V2 receptorXq28XRHyperthermia, polyuria, polydipsia, dehydration, inability to form concentrated urine, mental retardation if diagnosis delayed. Symptoms in infancyHyperosmolar plasma, dilute urine-
Autosomal dominant nephrogenic diabetes insipidus type 2 AQP212q13AD and ARPolyuria, polydipsia, dehydration, inability to form concentrated urine. Symptoms after first year of lifeHyperosmolar plasma, dilute urine-

AA: Aminoaciduria; AD:autosomal dominant; AR: autosomal recessive; LFT's: Liver function tests; LMWP: low molecular weight proteinuria; XD: X-linked dominant; XR: X-linked recessive; PTH: Parathyroid hormone