Hereditary tubulopathies

Tubulopathies are a heterogeneous group of diseases united by the presence of disorders in the tubular epithelium of the nephron of the functions of one or more protein enzymes, which cease to perform the function of reabsorption of one or more substances filtered from the blood through the glomeruli into the tubules, which determines the development of the disease. Primary and secondary tubulopathies are distinguished. Primary ones involve a hereditary defect in the genes that regulate the function of one or another tubular enzyme, as a result of which the pathology usually develops from the first months or years of the child's life. At present, far from all the 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 identify diseases in which the reabsorption capacity of the proximal and distal sections, collecting tubules, or all sections of the tubules is predominantly affected.

Classification of primary tubulopathies by defect localization.

• With predominant damage to the proximal tubules (de Toni-Debre-Fanconi disease and syndrome, glycinuria, cystinuria, phosphate diabetes, renal tubular acidosis type II (infantile), renal glucosuria, etc.).
• With predominant damage to the distal tubule (renal tubular acidosis type I, nephrogenic diabetes insipidus, pseudohypoaldosteronism).
• With impaired sodium reabsorption in the epithelial sodium channel of the cortical part of the collecting ducts with early development:
  • arterial hypertension (Liddle's syndrome, hyperaldosteronism, etc.);
  • arterial hypotension (Bartter, Gitelman syndromes).
• With damage to the entire tubular apparatus (nephronophthisis).

The optimal classification for a practicing physician is considered to be the one based on the identification of the leading clinical symptom complex. Currently, more than 30 different primary tubulopathies are known, their number increases as the pathophysiology of the kidneys is further studied. According to some authors, it is advisable to classify tubulopathies by the leading clinical manifestation. The classification given below does not claim to represent all existing hereditary tubulopathies and is limited to the most common diseases.

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

• Hereditary tubulopathies accompanied by polyuria.
  • Renal glucosuria.
  • Renal diabetes insipidus (pseudohypoaldosteronism):
    • X-linked recessive;
    • autosomal dominant;
    • autosomal recessive.
• Hereditary tubulopathies accompanied by skeletal deformation.
  • De Toni-Debré-Fanconi disease (autosomal dominant, autosomal recessive, X-linked inheritance).
  • Renal distal tubular metabolic acidosis type I:
    • classical, autosomal dominant;
    • autosomal recessive.
• Phosphate diabetes (hypophosphatemic rickets, vitamin D-resistant):
  • hypophosphatemic rickets X-linked dominant;
  • hypophosphatemic rickets autosomal dominant;
  • hypophosphatemic rickets with hypercalciuria autosomal recessive.
• Renal distal tubular metabolic acidosis type 1 (autosomal dominant, autosomal recessive).
• Renal proximal tubular metabolic acidosis type II (autosomal recessive with mental retardation and eye involvement).
• Combined distal and proximal renal tubular metabolic acidosis type III (autosomal recessive with osteoporosis).

• Hereditary tubulopathies accompanied by nephrolithiasis:
  • cystinuria;
  • primary hyperoxaluria;
  • glycinuria;
  • xanthunia;
  • alkaptonuria;
  • Dent's syndrome;
  • other.
• Hereditary tubulopathies occurring with arterial hypertension:
  • Liddle syndrome (autosomal dominant);
  • pseudohypoaldosteronism (Gordon syndrome);
  • "apparent" excess of mineralocorticoids.
• Hereditary tubulopathies accompanied by arterial hypotension:
  • Bartter syndrome type I (neonatal);
  • Bartter syndrome type II (neonatal);
  • Bartter syndrome type III (classic);
  • Bartter syndrome with deafness.
• Hereditary tubulopathies occurring with hypomagnesemia syndrome:
  • Iggelman syndrome;
  • familial hypomagnesemia syndrome with hypercalciuria, metabolic acidosis and nephrocalcinosis (autosomal recessive);
  • hypomagnesemia with secondary hypocalcemia (autosomal recessive);
  • isolated familial hypomagnesemia (autosomal recessive, autosomal dominant).

Among the numerous hereditary tubulopathies, de Toni-Debre-Fanconi syndrome and disease attract special attention due to the severity and sufficient prevalence of this pathology.

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