IllnessRenal-tubular acidosis, differential diagnosis

NGS +

Renal-tubular acidosis is the development of metabolic acidosis due to a defect in the renal tubules, either to absorb bicarbonate or to increase hydrogen excretion in response to acidemia. Four types are distinguished: Type 1 (distal; ATP6V0A4, ATP6V1B1, FOXI1, SLC4A1, WDR72 genes) inability to excrete hydrogen ions. Type 2 (proximal; SLC4A4 gene) Aggravated bicarbonate absorption when plasma bicarbonate is above a threshold value; often associated with generalized proximal tubular dysfunction (e.g. also in Lowe and Fanconi syndrome) with bicarbonaturia, glucosuria, phosphaturia, uricosuria, proteinuria, aminoaciduria. Type 3 (distal and proximal; CA2 gene) Rare cases of autosomal recessive osteopetrosis with renal-tubular acidosis. Type 4 (hypoaldosteronism; CYP11B2 gene) Disturbed ammonia synthesis and thus limited acid buffering. Both autosomal-recessive and autosomal-dominant inheritance is observed regrading the different inherited causes. The diagnostic sensitivity of the DNA tests has been sufficiently investigated for type 1; 15% of the cases have unknown genetic causes as well as largely unknown proportions in type 2-4. An inconspicuous genetic finding therefore does not mean a reliable exclusion of the suspected clinical diagnosis.

(Basic diagnostic genes: ###; additional gene: ###)

References: https://www.ncbi.nlm.nih.gov/books/NBK547595/

https://www.ncbi.nlm.nih.gov/books/NBK1127/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882136/?_ga=2.179720620.987290377.1606664293-187355794.1606060682

• Alias: Hereditary distal renal tubular acidosis
• Alias: Primary renal tubular acidosis
• Allelic: Amelogenesis imperfecta, type IIA3 (WDR72)
• Allelic: Blood groups, Diego, Froese, Swann, Waldner, Wright
• Allelic: Cryohydrocytosis (SLC4A1)
• Allelic: Malaria, resistance to (SLC4A1)
• Allelic: Ovalocytosis, SA type (SLC4A1)
• Allelic: Spherocytosis, type 4 (SLC4A1)
• Distal renal tubular acidosis 1 (SLC4A1)
• Distal renal tubular acidosis 2 with progressive sensorineural hearing loss (ATP6V1B1)
• Distal renal tubular acidosis 3 with/-out sensorineural hearing loss (ATP6V0A4)
• Distal renal tubular acidosis 4 with hemolytic anemia (SLC4A1)
• Enlarged vestibular aqueduct (FOXI1)
• Fanconi renotubular syndrome 3 (EHHADH)
• Metabolic acidosis, glucosuria, phosphaturia, aminoaciduria + proteinuria (EHHADH)
• Osteopetrosis, AR 3, with renal tubular acidosis (CA2)
• Renal tubular acidosis, proximal, with ocular abnormalities (SLC4A4)