Pediatric Medical Genetics - S.I. Smiian 2003

Hereditary Nephropathies
Renal Tubular Acidosis (Lightwood-Butler-Albright Syndrome)

This is a specific tubular defect that causes the Kidneys to fail to maintain the body's acid-base balance. It is inherited in an autosomal recessive manner and is rare. There are two types of renal tubular acidosis: Type I, an acidosis resulting from impaired H⁺ ion transport in the distal tubules ("adult form", "fixed acidosis", Butler-Albright syndrome), and Type II, an acidosis resulting from the failure of the proximal tubules to reabsorb bicarbonates (infantile, transient form, Lightwood syndrome).

The diagnostic criteria for both types of the disease include the following:

1. Polyuria, polydipsia, hyposthenuria.

2. Severe metabolic acidosis accompanied by a significant deficit of Blood bicarbonates.

3. Alterations in blood ionogram (hypokalemia, hypocalcemia, hyperchloremia, etc.).

4. Delayed physical development in children.

5. Nephrocalcinosis, Nephrolithiasis (in 30% of cases).

6. Osteopathies with Osteoporosis and Rickets-like bone changes.

7. Development of secondary Pyelonephritis.

Despite similar clinical presentations, both types of the disease also have distinct differences.

Type I (distal acidosis) typically manifests no earlier than 3 years of age, more commonly in girls (70%). In addition to the metabolic changes already mentioned, there are severe Water-electrolyte balance disorders, and hypercalciuria is frequently observed. Osteoporosis and severe osteopathy—manifesting as knock-knees accompanied by limb pain—are almost constant symptoms. Physical growth retardation is more pronounced than in the proximal type. Nephrocalcinosis, nephrolithiasis, and pyelonephritis more frequently complicate the course of this form of renal tubular acidosis.

The diagnostic criteria for Type I of the disease are as follows:

1. Growth retardation.

2. Rickets-like bone changes.

3. Dehydration crises, polyuria.

4. Nephrocalcinosis, urolithiasis, interstitial nephritis, pyelonephritis.

5. Alkaline urine reaction.

6. Persistent base deficit in the blood.

Type II (proximal acidosis) may appear as early as one month of age, often triggered by introducing cottage cheese or cow's milk—which are rich in phosphates and sulfates—into the child's diet. Affected children develop anorexia, vomiting, constipation, exicosis, restlessness, irritability, and unexplained fever. Examination reveals polyuria, polydipsia, signs of hypokalemia (adynamia, decreased Muscle tone, intestinal paresis), and developmental delay.

Rickets-like skeletal changes—such as leg bowing—appear early, and nephrocalcinosis and nephrolithiasis frequently develop. Despite the severe clinical course, spontaneous recovery is possible.

The diagnostic criteria for Type II renal tubular acidosis are as follows:

1. Onset of the disease within the first months of life.

2. Unexplained vomiting and fever.

3. Severe, progressive rickets-like bone changes.

4. Delayed physical development.

5. Hypercalciuria, hypokalemia.

Treatment should be aimed at correcting acidosis and electrolyte imbalances, as well as preventing osteopathies. A potato-based diet and high fluid intake are prescribed, while the consumption of animal protein is restricted.

Metabolic acidosis is corrected by administering sodium bicarbonate solutions; however, rapid correction is not only unjustified but also harmful if the bicarbonate deficit is significant, as this poses a risk of respiratory alkalosis.

During the first 12 hours, it is recommended to correct the bicarbonate deficit only partially (by approximately one-third), and over the subsequent 36 hours — the remaining deficit. The approximate amount of bicarbonate required for administration can be calculated using the formula:

Class="center">НСО₃ (mmol) = ВЕ (blood bicarbonate deficit) х 1/3 body weight (kg)

It should be kept in mind that 100 ml of a 1.4% sodium bicarbonate solution contains 15 mmol, while 100 ml of a 5% solution contains about 60 mmol of НСО₃.

During acidosis correction, it is essential to continuously monitor blood potassium levels to keep them within the range of 4–5.5 mmol/L. If potassium drops to 3 mmol/L, potassium supplements must be administered. To correct hypocalcemia, it is recommended to intravenously administer 10 ml of 10% calcium gluconate every 4 hours until blood levels normalize. To treat acidosis, oral administration of various citrate mixtures has also been proposed: 140 g of citric acid and 98 g of sodium citrate per 1 L of distilled water. 1 ml of this solution contains 1 mmol of НСО₃. The solution is prescribed in a dosage of 50–100 ml per day, divided into 3 doses:

For Osteomalacia, calcium salts and vitamin D are prescribed at a dose of 50,000 IU per day until ossification processes improve. For calcium oxalate urolithiasis, long-term oral administration of magnesium oxide at a dose of 150–200 mg per day is used (for up to 5 years).

The prognosis worsens with the onset of secondary pyelonephritis and urolithiasis, particularly in the presence of a progressive decline in the Glomerular Filtration rate and The Development of Chronic Kidney Disease. In the absence of these complications, patients with renal tubular acidosis can have a normal life expectancy. In type II (proximal) renal tubular acidosis, spontaneous recovery is frequently observed by 12–18 months of age.