What is "tubulopathy"

n. (context pathology English) Any disease of the renal tubules of the nephron

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.

Characteristics of Some Inherited Tubulopathies

Disorder [OMIM Number]

Protein Defect

Chromosome Localization

Inheritance

Clinical Features/Notes

Biochemical Features

Proximal Tubule

Lowe's syndrome (oculocerebral dystrophy [309000]

OCRL1

Xq26.1

XR

Hydrophthalmia, cataract, mental retardation, hyporeflexia, hypotonia and progressive kidney failure, normotensive

Plasma: ↓K, ↓CO; Urine: ↑LMWP, ↑AA, ↑PO, ↑K

Wilson's disease [277900]

ATP7B

13q14.3-q21.1

AR

Liver disease or neurologic symptoms, or both, Kayser-Fleischer rings, normotensive

Plasma: ↑free copper, abnormal LFTs; Urine: ↑copper excretion, ↑LMWP, ↑AA, ↑PO, ↑Glycosuria

Dent's disease (X-linked recessive hypophophatemic rickets)[300009]

CLCN5

Xp11.22

XR

Nephrocalcinosis, nephrolithiasis, rachitic and osteomalacic bone disease, progressive kidney failure, normotensive

Plasma: ↓PO, N/↓K; Urine: ↑LMWP, ↑AA, ↑K, ↑Ca, ↑PO, ↑Glycosuria

X-linked dominant hypophosphatemic rickets [307800

PHEX

Xp22.2-p22.1

XD

Growth retardation, rachitic and osteomalacic bone disease, hypophosphatemia, and renal defects in phosphate reabsorption and vitamin D metabolism

Plasma: ↓PO, ↑ALP; Urine: ↑PO

Loop of Henle

Bartter's syndrome

NKCC2 (type 1)

15q15-21.1

AR

Polyuria, polydipsia, muscle weakness, hypovolemia, normotensive or hypotensive (all types). Maternal polyhydramnios, premature birth, perinatal salt wasting, nephrocalcinosis and kidney stones (type 1 and 2), milder phenotype with normocalciuria(type 3), sensorineural deafness, motor retardation, renal failure (type 4)

Plasma: ↑renin, ↓K, ↑CO, mild ↓Mg in some patients; Urine: ↑Ca

[601678]

ROMK (type 2)

11q24

AR

[241200]

C1C-Kb (type 3, classic)

1p36

AR

[607364]

1p31

AR

[602522]

Barttin (type 4)

Hypomagnesemic hypercalciuric nephrocalcinosis (magnesium-losing kidney)[248250]

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[177200]

ENaC (activating)

16p13-p12

AD

Early, and frequently severe, hypertension, stroke

Plasma: ↓renin, ↓K, ↓Mg, ↑CO; Urine: ↑K

Pseudohypoaldosteronism type 1a [264350]

ENaC (inactivating)

12p13, 16p13-p12

AR

Presents in infancy with salt-wasting and hypotension, Cough, respiratory infections

Plasma: ↑renin, ↓Na, ↑K, ↓CO; Urine: ↑K

Pseudohypoaldosteronism type 1b [177735]

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, ↓CO; Urine: ↑K

Pseudohypoaldosteronism type 2 ( Gordon's syndrome) [145260]

Unknown (?WNK)

1q31-q42, 12p13, 17q21-q22

AD

Hypertension (± muscle weakness, short stature, intellectual impairment). Correction of physiologic abnormalities by thiazide diuretics

Plasma: ↓renin, ↑K, ↓CO, ↑Cl; Urine: ↓K

Gitelman's syndrome [263800]

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, ↑CO; Urine: ↓calcium:creatinine excretion ratio (useful in distinguishing Gitelman's and Bartter's)(Note: biochemically can mimic thiazide use)

X-linked nephrogenic diabetes insipidus type 1 [304800]

V2 receptor

Xq28

XR

Hyperthermia, polyuria, polydipsia, dehydration, inability to form concentrated urine, mental retardation if diagnosis delayed. Symptoms in infancy

Hyperosmolar plasma, dilute urine

Autosomal dominant nephrogenic diabetes insipidus type 2 [192340]

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