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 defect	Chromosome localization	Inheritance	Clinical features/notes	Biochemical features	-
Proximal tubule						-
Lowe's syndrome	CLCN5	Xp11.22	XR	Nephrocalcinosis, nephrolithiasis, rachitic and osteomalacic bone disease, progressive kidney failure, normotensive	Plasma: ↓PO₄, N/↓K; urine: ↑LMWP, ↑AA, ↑K, ↑Ca, ↑PO₄, ↑glycosuria	-
X-linked dominant hypophosphatemic rickets	ROMK	11q24	AR	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
	C1C-Kb	1p36	AR	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
		1p31	AR	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
	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	PCLN1	3q27	AR	Nephrocalcinosis, renal failure, ocular/hearing defects, polyruria, polydipsia, recurrent urinary tract infections, recurrent renal colic, normotensive	Plasma: ↓Mg, ↑PTH; urine: ↑Ca, ↑Mg	-
Distal tubule/collecting duct						-
Liddle's syndrome	ENaC	16p13-p12	AD	Early, and frequently severe, hypertension, stroke	Plasma: ↓renin, ↓K, ↓Mg, ↑CO₂; urine: ↑K	-
Pseudohypoaldosteronism type 1a	ENaC	12p13, 16p13-p12	AR	Presents in infancy with salt-wasting and hypotension, cough, respiratory infections	Plasma: ↑renin, ↓Na, ↑K, ↓CO₂; urine: ↑K	-
Pseudohypoaldosteronism type 1b	Mineralocorticoid receptor	4q31.1	AD	Presents in infancy with salt-wasting and hypotension. Milder than type 1a and remits with age	Plasma: ↑renin, ↓Na, ↑K, ↓CO₂; urine: ↑K	-
Pseudohypoaldosteronism type 2	Unknown	1q31-q42, 12p13, 17q21-q22	AD	Hypertension. Correction of physiologic abnormalities by thiazide diuretics	Plasma: ↓renin, ↑K, ↓CO₂, ↑Cl; urine: ↓K	-
Gitelman's syndrome	NCCT	16q13	AR	Hypotension, weakness, paresthesias, tetany, fatigue, and salt craving, presentation generally much later in life than in Bartter's and hypocalciuria is typical	Plasma: ↑renin, ↓K, ↓Mg, ↑CO₂; urine: ↓calcium:creatinine excretion ratio	-
X-linked nephrogenic diabetes insipidus type 1	V2 receptor	Xq28	XR	Hyperthermia, polyuria, polydipsia, dehydration, inability to form concentrated urine, intellectual disability if diagnosis delayed. Symptoms in infancy	Hyperosmolar plasma, dilute urine	-
Autosomal dominant nephrogenic diabetes insipidus type 2	AQP2	12q13	AD and AR	Polyuria, polydipsia, dehydration, inability to form concentrated urine. Symptoms after first year of life	Hyperosmolar plasma, dilute urine	-

AA: aminoaciduria; AD: autosomal dominant; AR: autosomal recessive; LFTs: liver function tests; LMWP: low molecular weight proteinuria; XD: X-linked dominant; XR: X-linked recessive; PTH: parathyroid hormone