Vitamin D-resistant rickets (vitamin D-resistant rickets) has two types: hypophosphatemic and hypocalcemic. This section mainly discusses the more common hypophosphatemic vitamin D-resistant rickets, also known as familial hypophosphatemia (familial hypophosphatemia), or renal hypophosphatemic rickets (renal hypophosphatemic rickets). The characteristics of this disease are:

1. low blood phosphorus levels, with no response to ordinary doses of vitamin D;
2. increased urinary phosphorus;
3. poor calcium absorption from the intestines, with reduced or normal urinary calcium;
4. rickets symptoms appearing after one year of age;
5. slow growth, although older children who develop the disease may have normal growth.

bubble_chart Etiology

It is caused by reduced renal tubular reabsorption of phosphorus. Poor intestinal absorption of calcium and phosphorus leads to decreased blood phosphorus levels, ranging from 0.65 to 0.97 mmol/L (2–3 mg/dl), with the calcium-phosphorus product mostly below 30, making bone calcification difficult.

Genetically, it manifests as X-linked dominant inheritance. Male patients can only pass this Bingchuan to their daughters. Female patients can transmit it to both sons and daughters. Female patients are more numerous but exhibit milder symptoms, often presenting only with low blood phosphorus levels without obvious rickets skeletal changes. The incidence is lower in males, but symptoms are more severe. Occasionally, some cases belong to autosomal recessive inheritance. There are also sporadic cases with no family history.

bubble_chart Clinical Manifestations

Symptoms often begin to appear when the lower limbs start bearing weight around the age of one. The earliest signs are typically "O" shaped legs or "X" shaped legs, while other rickets symptoms are mild. Features such as rachitic rosary and Harrison's groove are less common, and the muscle hypotonia typically seen in nutritional vitamin D deficiency rickets is absent. These signs often go unnoticed by parents. In more severe cases, progressive bone deformities and multiple fractures may occur, accompanied by bone pain, especially in the lower limbs, which can even impair walking. Severe deformities often affect height growth. Poor tooth quality, toothache, and easily lost teeth that are slow to regenerate are also observed.

X-ray films reveal varying degrees of rickets changes, with active lesions coexisting with those in the stage of convalescence, most easily detected in the femur and tibia. Laboratory findings primarily show hypophosphatemia, mostly around 0.65 mmol/L (2 mg/dL), while serum calcium may be within the normal range or slightly low. Routine urine tests and renal function are normal, with no amino acids in the urine. The renal tubular reabsorption rate of phosphate is reduced.

bubble_chart Treatment Measures

The treatment principle is to prevent bone deformity, increase blood phosphorus as much as possible, and maintain it above 0.97 mmol/L (3 mg/dl) to facilitate bone calcification. It is also essential to maintain normal growth rates while avoiding hypercalciuria and hypercalcemia caused by vitamin D toxicity. The advantages and disadvantages of various measures are briefly described below:

1. **Oral phosphate alone**: To raise blood phosphorus to normal levels, phosphate preparations are often required. A common formulation is 18 g of sodium dihydrogen phosphate and 145 g of disodium hydrogen phosphate, diluted in 1000 ml of water, taken at 15–20 ml per dose, five times daily, providing 2 g of elemental phosphorus per day. Phosphate preparations have an unpleasant taste and may cause diarrhea. To enhance intestinal phosphorus absorption, vitamin D or DHT should ideally be administered concurrently.
2. **Combined phosphate and vitamin D therapy**: The dosage of vitamin D ranges from 10,000 to 50,000 IU/day, with a maximum of 100,000 IU/day. Vitamin D tends to accumulate in body fat, and toxicity symptoms may only manifest after significant storage, making overdose a risk. DHT, a vitamin D analog, Neijing exerts vitamin D-like effects after hydroxylation in the body but does not accumulate in fat, reducing the risk of toxicity and improving safety. Initially, a dose of nearly 2 mg/day is required for 2–4 weeks, followed by a maintenance dose of 0.5–1.5 mg/day to control the condition. After treatment, plasma alkaline phosphatase normalizes, but blood phosphorus remains low, necessitating concurrent phosphate supplementation. Potassium phosphate is more palatable among phosphate preparations, though it may lower blood calcium if taken alone. Combining 1.25(OH)₂D₃ at 0.75–1 μg/day with phosphate therapy yields better outcomes.

To prevent hypercalcemia, 24-hour urinary calcium and creatinine should be monitored every 1–3 months. The normal urinary calcium-to-creatinine ratio is 0.15–0.3. A ratio exceeding 0.4 indicates excessive vitamin D or DHT dosage, warranting early dose reduction to minimize toxicity risk. Some advocate using diuretics such as hydrochlorothiazide at 1.5–2 mg/kg/day, divided into multiple doses, to avoid hypercalcemia and significantly increase blood phosphorus levels.

bubble_chart Differentiation

The differentiation between this disease and vitamin D-deficient rickets lies in the following characteristics:

1. The intake of vitamin D exceeds the general requirement, yet active rickets skeletal changes still occur;
2. Active manifestations of rickets persist beyond the age of 2–3 years;
3. Administering 400,000–600,000 IU of vitamin D orally or intramuscularly once typically results in increased blood phosphorus levels within days and improvement in long-bone X-rays within two weeks for children with general D-deficient rickets, whereas patients with this disease show no such changes;
4. Family members often exhibit hypophosphatemia, which is a hallmark of hypophosphatemic vitamin D-resistant rickets.

This disease must also be distinguished from hypocalcemic vitamin D-resistant rickets. The latter, also known as vitamin D-dependent rickets (vitamin D dependent rickets), is rare and results from a deficiency of the renal 1-hydroxylase enzyme, impairing the synthesis of 1,25(OH)₂D. Symptoms typically appear within months after birth and are often accompanied by muscle weakness, with early-onset hand and foot convulsions. Blood calcium levels are low, phosphorus levels are normal or slightly low, and chloride levels are elevated, with possible aminoaciduria. Despite conventional doses of vitamin D therapy, X-rays of long bones still show signs of rickets. Increasing the vitamin D dosage to 10,000 IU daily or administering dihydrotachysterol (DHT) 0.2–0.5 mg is required for efficacy. Treatment with 0.25–2 μg of 1,25(OH)₂

Additionally, this disease must be differentiated from Fanconi syndrome and renal tubular acidosis.