Vitamin D Metabolism
1.25 (OH) Vit D
• As the serum concentration of calcium (Ca) and phosphorus (PO4) decreases, it increases.
• Increases intestinal absorption of Ca and PO4
• It increases the absorption of Mg from the intestine.
• Increases the mobilization of Ca and PO4 from the bone.
24.25 (OH) Vit D
• The serum concentration of Ca and PO4 increases as it rises.
• It allows Ca and PO 4 to precipitate in the osteoid tissue.
25(OH)2 Vit D
• The 25 (OH) level in the blood is the parameter that best reflects the vitamin D status in humans.
Rickets (Richitis)
• Rickets is a metabolic bone disease that occurs due to the deterioration in the concentration of calcium and phosphorus ions in the extracellular fluid, and the deposition of calcium phosphate salts in the bone.
Rickets Etiological Classification
1. Calcipenic Rickets:
Rickets due to Vitamin D deficiency
• Congenital rickets (maternal osteomalacia, hypophosphatasia)
• Insufficient vitamin D intake with food (meat and milk-poor diet)
• Not being exposed to sufficient sun rays (mother or baby)
• Vitamin D malabsorption (pathologies causing fat malabsorption)
Situations where the need for Vitamin D is increased
• Prematurity
• Anticonvulsant use (Vitamin D metabolism accelerates)
Inability to convert Vitamin D to its active metabolites
• Chronic liver disease
• Chronic kidney disease
• Strontium, aluminum, lead, mercury, cadmium intoxication (reduces 1-a-hydroxylase activity in the kidneys)
Vitamin D dependent rickets
• Type 1
• Type 2
2. Phosphopenic Rickets
• Hereditary primary hypophosphatemia
• Hereditary hypophosphatemic hypercalciuric rickets (HHHR)
• Fanconi Syndrome
Rickets due to vitamin D deficiency
Clinic:
• Rickets due to Vitamin D deficiency is most common between the ages of 3 months and 2 years.
• It can also be seen in premature babies. Subclinical rickets may occur due to accelerated growth in adolescence.
• Vitamin D deficiency in the mother is an important risk factor.
• It is most common in winter and spring.
Ossification (calcification) disorder
• Findings are most common in rapidly growing bones (upper extremity, skull and ribs). Sweating, craniotabes, and wide anterior fontanelle are early signs. Cartilage maturation is delayed due to decreased calcification in the bone matrix. Accordingly, rachitic rosary, pectus excavatus, genu valgum/varum, thickening of the parietal bones and caput quadratum occur. The eruption of teeth is delayed.
The costochondral joints are enlarged (rachitic rosary):
• The attachment areas of the ribs to the diaphragm are pulled inward to form the "Harrison groove".
Hypocalcemia:
• Tetany, muscle weakness, convulsions.
Rachitic pneumopathy:
• Frequent lung infections and rickets pneumopathy develop as a result of respiratory muscle weakness. The abdomen swells (frog belly) due to decreased tone in the abdominal muscles. Sitting and walking are delayed due to general hypotonia.
Deformities that develop as they grow:
• Scoliosis, dorsolumbar kyphosis, pectus carinatum, genu varum, genu valgum, coxa vara deformities and asymmetry in the head develop. In female patients, stenosis at the entrance of the pelvis may cause problems during delivery in the future. The epiphyses of the wrists and ankles are enlarged. Green tree fractures may occur.
Diagnosis:
• Diagnosis is made by history, physical examination, biochemical analysis and radiography.
• Serum calcium is normal or low, serum phosphorus is below 4 mg/dl, serum Al-kalene phosphatase is increased, cyclic adenosine monophosphate (cAMP) is increased in urine and serum 25 hydroxycholecalciferol level is decreased, 1,25-(OH)2D3 is normal or increased, Parathormone may be found to be increased.
• Rickets is examined in 3 periods according to biochemical data.
Serum (Ca, P, ALP, PTH, 1.25 Vit D), Urine (P, Camp, Aminoaciduria)
1st semester; all are normal in serum and urine (only Ca is low)
2nd semester; all are high (only Ca is normal and P in serum is low)
3rd Term; all are high (only Ca, P, 1.25 Vit D low)
• On the wrist X-ray taken to evaluate the radiological findings; Irregularity, brushy appearance and concavity can be seen at the distal end of the radius and ulna. Expansion of the rib ends, concavity, and rachitic pneumopathy in the lung can be detected in the chest X-ray.
Treatment
• There are two approaches in the treatment of nutritional vitamin D.
1. Stoss treatment: High dose (300,000-600,000) can be given orally (preferred) or intramuscularly in 2-4 doses within 1 day.
2. A minimum of 2000 IU of vitamin D daily is given for at least 3 months. At the end of this period, 400 IU vitamin D maintenance therapy is continued in children aged less than1 year and 600 for more than 1 year old. If it does not respond to treatment, it is Vitamin D-dependent rickets or there is an underlying metabolic disease. Further research is required.
• Adequate calcium (500 mg/day) and phosphorus should be given with diet during treatment. Oral calcium should be continued for 2-6 weeks after IV calcium bolus in children with symptomatic hypocalcemia.
Type 1 Vitamin D Dependent Rickets
• In the type IA form, the main biochemical defect is the deficiency in the enzyme la-hydroxylase, which converts 25(OH)D3 to 1,25(OH\D3.
• The responsible gene is on the long arm of the 12th chromosome. It shows autosomal recessive inheritance.
• Plasma 1.25 (OH\ D3 concentration is low, 1,25(OH)2 D3 production does not increase in response to parathormone stimulation. 25OH Vitamin D levels are normal.
• 0.5-2 mcg/day 1.25 (OH) D3 is given in treatment.
• In the type 1B form, because there is a mutation in the 25 hydroxylase gene; 25 OHD levels are low, but 1.25 (OH)2 D3 levels are normal. Vitamin D2 3000 U/day is used in the treatment.
Type 2 Vitamin D Rickets Dependent
• It is autosomal recessive.
• In the type 2A form, there is resistance to Vitamin D at the receptor level in the target organ. Type 2B develops as a result of overexpression of an HRE-binding protein that interferes with the effects of 1,25 vitamin D. The clinical picture is similar to Type I.
• However, there is alopecia.
• Findings begin to appear from the 6th month of life.
• Plasma 1.25(0H) 2 D3 concentration is too high.
• High dose 1.25 (OH) D3 (up to 50-60 mcg per day) and calcium are given in treatment.
X-Linked Hypophosphatemic Rickets (Genetic Primary Hypophosphatemic Rickets)
• Hereditary Vitamin D is the most common cause of resistant hypophosphatemic rickets. X-linked dominant.
pathogenesis
• As a result of the mutation in the PHEX gene, the breakdown of FGF-23 (phosphatonin) is reduced.
• As a result of excess FGF-23 in the body, tubular phosphate reabsorption is impaired and active vitamin D production decreases because 1 alpha hydroxylase activity is inhibited.
• Rickets due to FGF-23 excess may also be seen in some secondary causes (neurdfibromatosis, McCune Albright syndrome, tumors, epidermal nevus syndrome).
Clinic:
• Boys have a more severe picture than girls.
• Although craniocytosis, frontal or occipital dislocation may occur in early childhood, it is usually clinically normal.
• Harrison's groove, rachitic rosary, vertebral anomalies, decrease in muscle strength, and tetany, which are findings related to hypocalcemia, are not observed. " Patients usually present with growth retardation and deformity from the age of 3 years.
• When the child starts walking, shape changes such as genu varum (rarely genu valgum) and coxa vara are observed in the weight-bearing extremity.
• The eruption of teeth is delayed, dentin development is impaired. Spontaneous dental abscesses are common.
• Serum calcium and PTH levels are normal. Alkaline phosphatase is increased.
• There is no aminociduria, glycosuria, bicarbonaturia. Increased urinary phosphate excretion.
• 1.25(0H)2 D3 is not increased, normal or low despite severe hypophosphatemia.
Treatment: Oral phosphate and active vitamin D are used.
Hereditary Hypercalciuric Hypophosphatemic Rickets
• It shows autosomal recessive inheritance.
• Sodium-phosphate cotransport (SLC3A43) is impaired in the proximal tubule.
• The clinical picture is similar to X-linked hypophosphatemic rickets, but renal 1-alpha hydroxylase activity is normal in this disease.
• High serum level of 1.25(0H)2 D3 and associated hypercalciuria are seen in these patients. Excessively increased renal phosphate excretion stimulates 1-alpha hydroxylase and synthesis of 1,25-(0H\D3 is increased.
• Parathormone level is low.
• With phosphate treatment alone, clinical and radiological improvement is achieved, urinary Ca excretion decreases, plasma 1.25-(0H\ D3 concentration decreases to normal.
• The use of vitamin D is contraindicated in this disease.
