Case history
Case history #1
The parents of a 30-month-old boy become concerned about his relative frailty and small size. On examination, his growth is below the second percentile for height, and he had moderate weakness and some bowing at the knees. An arterialised venous blood sample shows that both the pH (at 7.23) and the total CO₂ (at 14 mmol/L [14 mEq/L]) are low. Urinalysis finds a low urine pH, but is positive for glucose. Further studies define non-gap metabolic acidosis, amino aciduria, hyperphosphataemia and hypophosphaturia, and hyperuricosuria. When the patient is given bicarbonate intravenously to raise the serum bicarbonate above 20 mmol/L (20 mEq/L), the urine pH rises and bicarbonate appears in the urine. The fractional excretion of bicarbonate is calculated at this time and is significantly elevated. The patient has normal vitamin D levels, and responds to citric acid/sodium citrate supplementation with recovery of skeletal growth.
Case history #2
A 22-year-old man is found to have nephrocalcinosis on an abdominal x-ray. Further evaluation shows mild hyperchloraemic metabolic acidosis with a normal serum anion gap and a urine pH over 5.5. He is also found to have sensorineural hearing loss. Genetic studies reveal a mutation of the gene SLC4A1.
Other presentations
Adults with diabetes and chronic kidney disease can present with hyperkalaemia and hyperchloraemic metabolic acidosis in the absence of drugs known to cause hyperkalaemia (e.g., beta-blockers, heparin, potassium sparing diuretics, trimethoprim, and non-steroidal anti-inflammatory drugs). Measurement of serum renin and aldosterone levels may show that the concentrations of both of these hormones are depressed (hyporeninaemic hypoaldosteronism), or that the aldosterone concentration is low but the serum renin is normal. The urine pH is appropriately low (below 5.0), but the urine anion gap is positive, indicating that no ammonium is present in the urine. Patients with Addison's disease present with hyperchloraemic and hyperkalaemic metabolic acidosis and a positive urine anion gap due to the absence of urinary ammonium. Serum cortisol is also depressed in this instance.
Adults with acquired Fanconi syndrome do not have the skeletal findings present in children, but do have similar urinary findings and an identical response to bicarbonate administration. In adults, a typical clinical presentation is the discovery of hyperchloraemic metabolic acidosis after standard laboratory testing or while evaluating weakness or fatigue related to an associated hypokalaemia. Alternatively, adults or children may simply show a serum bicarbonate concentration <15 mmol/L (<15 mEq/L), and a high fractional excretion of bicarbonate after bicarbonate loading (isolated proximal RTA). Further testing reveals hypophosphataemia, glycosuria, and proteinuria. Bicarbonaturia may then be demonstrated during bicarbonate infusion. Careful questioning may reveal prior exposure to a heavy metal, outdated tetracycline medication, chemotherapy treatment, a history of abnormal urinary protein excretion, or the clinician may already be aware of these risk factors. Adults living in the Balkan region are also at risk.[9][10] People from the northern part of Thailand are at increased risk for hyperkalaemic distal RTA.[11]
Primary Sjogren's syndrome has been associated with hypokalaemic distal RTA. It has been reported that up to 40% of patients with Sjogren's syndrome may have distal RTA, and the primary presentation may be hypokalaemic paralysis.[12]
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