Hereditary tubulopathies

Tubulopathy is a heterogeneous group of diseases combined by the presence of disorders in the tubular epithelium of the nephron functions of one or more enzyme proteins that cease to function as a reabsorption of one or several substances filtered from the blood through the glomeruli into tubules, which determines the development of the disease. There are primary and secondary tubulopathies. The primary ones involve a hereditary defect of the genes that regulate the function of a particular tubular enzyme, resulting in the development of pathology usually from the first months or years of life of the child. Currently, not all genes are known, the mutation of which leads to the development of hereditary tubulopathies.

There are several classifications of primary (hereditary) tubulopathies.

One option is to isolate diseases in which the reabsorption capacity of the proximal and distal segments, collecting tubes or all sections of the tubules is predominantly affected.

Classification of primary tubulopathies for defect localization.

• With the primary lesion of the proximal tubules (disease and de Toni-Debreu-Fanconi syndrome, glycinuria, cystinuria, phosphate-diabetes, renal tubular acidosis of type II (infant), renal glucosuria, etc.).
• With the predominant involvement of the distal tubule (renal tubular acidosis type I, nephrogenic diabetes insipidus, pseudohyperdosteronism).
• With the violation of sodium reabsorption in the epithelial sodium channel of the cortical part of the collecting tubules with early development:
  • arterial hypertension (Liddle syndrome, hyperaldosteronism, etc.);
  • arterial hypotension (Bartter syndrome, Gitelman syndrome).
• With damage to the entire tubular apparatus (nephronophytosis).

Optimal for a practical physician is considered a classification based on the isolation of the leading clinical symptom complex. At present, more than 30 different primary tubulopathies are known, their number increases with further study of the pathophysiology of the kidneys. According to some authors, it is advisable to classify tubulopathy according to the leading clinical manifestation. The classification below does not purport to represent all existing hereditary tubulopathies and is limited to the most common diseases.

Classification of hereditary tubulopathies according to the leading clinical symptom (syndrome).

• Hereditary tubulopathies, proceeding with polyuria.
  • Renal glucosuria.
  • Kidney diabetes insipidus (pseudohypoaldosteronism):
    • X-linked recessive;
    • autosomal dominant;
    • autosomal recessive.
• Hereditary tubulopathies, proceeding with deformation of the skeleton.
  • Disease de Toni-Debreu-Fanconi (autosomal dominant, autosomal recessive, X-linked type of inheritance).
  • Renal distal tubular metabolic acidosis of type I:
    • classical, autosomal dominant;
    • autosomal recessive.
• Phosphate-diabetes (hypophosphatemic rickets, vitamin D-resistant):
  • hypophosphatemic rickets X-linked dominant;
  • hypophosphatemic rickets are autosomal dominant;
  • hypophosphatemic rickets with hypercalciuria are autosomal recessive.
• Renal distal tubular metabolic acidosis of type 1 (autosomal dominant, autosomal recessive).
• Renal proximal tubular metabolic acidosis of type II (autosomal recessive with mental retardation and eye damage).
• Combined distal and proximal renal tubular metabolic acidosis of type III (autosomal recessive with osteoporosis).

• Hereditary tubulopathies occurring with nephrolithiasis:
  • cystinuria;
  • primary hyperoxaluria;
  • glycinuria;
  • xanthturia;
  • alkaponuria;
  • Dent's syndrome;
  • others.
• Hereditary tubulopathies, proceeding with arterial hypertension:
  • Liddle syndrome (autosomal dominant);
  • pseudohyperdosteronism (Gordon's syndrome);
  • "Imaginary" excess of mineralocorticoids.
• Hereditary tubulopathies, proceeding with arterial hypotension:
  • Bartter's syndrome type I (neonatal);
  • Bartter's syndrome type II (neonatal);
  • Bartter's syndrome type III (classical);
  • Bartter's syndrome with deafness.
• Hereditary tubulopathies, with hypomagnesemia syndrome:
  • Iggelman's syndrome;
  • family hypomagnesemia syndrome with hypercalciuria, metabolic acidosis and nephrocalcinosis (autosomal recessive);
  • hypomagnesemia with secondary hypocalcemia (autosomal recessive);
  • isolated family hypomagnesemia (autosomal recessive, autosomal dominant).

Among numerous hereditary tubulopathies, special attention is drawn to the syndrome and de-Tony-Debreu-Fanconi's disease in connection with the severity and sufficient prevalence of this pathology.

[1], [2], [3], [4], [5], [6], [7]