National University Faculty of Medicine RICKETS. Dr. Gehan M. Osman MBBS, MD Pediatrics Jaffar Ibn Auf Specialized Hospital

Transcription

1 National University Faculty of Medicine RICKETS Dr. Gehan M. Osman MBBS, MD Pediatrics Jaffar Ibn Auf Specialized Hospital

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6 DEFINITION o Rickets is consequence of the vitamin D deficit and may occur due to calcium and phosphorus metabolic disorders. Blood analysis shows hypophosphatemia. Histology- Failure in mineralisation of the bone and cartilaginous tissues. Clinical- manifests as skeletal growth disorder. hypocalcemia and

7 HISTORY Rickets ( from Greek word meaning spinal column ) was known since the first years of the human generation. It is described by Soran Efess (A.D) and by Galen ( A.D). It is described in detail by a British anatomist and orthopedician, Glisson in Incidence: Rickets is frequently in premature children and the children fed only wheat floor. In Moldova diagnosis was confirm in 35.5%, X-Ray 21.5% (A.Voloc, M.Garabedian, 1996)

8 RICKETS Disorder of mineralization of the bone matrix / osteoid in growing bone Involved: growth plate Newly trabecular formed Cortical bone Osteomalacia After cessation of growth Involves only a bone, not the growth plate

9 What is Rickets? Calcipaenic Rickets Phosphopaenic Rickets Vitamin D Related Rickets - Vitamin D Deficiency - Impaired Hepatic 25-hydroxylation - Impaired Renal 1α-hydroxylation of 25 (OH)D - End organ resistance to 1,25(OH)2D Rickets due to Dietary Calcium Deficiency Raised PTH Hypophosphataemic Rickets - X-linked Dominant (PHEX gene mutation) - Autosomal Dominant (FGF23 mutation) - Autosomal Recessive Type 1 (DMP1mutation) - Autosomal Recessive Type 2 (ENPP1mutation) - With Hypercalciuria (SLC34A3 gene mutation) - Associated with: (a) McCune-Albright syndrome (b) Tumour induced osteomalacia (c) Linear nevus sebaceous syndrome Renal Phosphate Wastage Hypophosphatemia Impaired Apoptosis of Terminally Differentiated Chondrocytes in the Growth Plate

10 RISK FACTORS Living in northern latitudes (>30o); Dark skinned children; Decreased exposure to sunlight Maternal vitamin D deficiency; Diets low in calcium, phosphorus and vit. D Prolonged parenteral nutrition in infancy with an inadequate supply of intravenous calcium and phosphate; Intestinal malabsorption

11 1. Lack of sunshine due to: Lack of outdoor activities Lack of ultraviolet light in fall and winter Too much cloud, dust, vapour and smoke

12 2. Improper feeding: 2.1 Inadequate intake of Vitamin D Breast milk 0-10IU/100ml Cow s milk 0.3-4IU/100ml Egg yolk 25IU/average yolk Herring 1500IU/100g 2.2 Improper Ca and P ratio

13 3. Fast growth, increased deficiency) requirement (relative 4. Diseases and drug: Liver diseases, renal diseases Gastrointestinal diseases Antiepileptic Glucocorticosteroid

14 Intestinal malabsorption: defective production of 25(OH)D3 liver disease. Increased metabolism of 25(OH)D3 enzyme induction by anticonvulsants; Defective production of 1,25(OH)2D3 Hereditary type I vitamin D-resistant (or dependent) rickets (mutation which abolishes activity of renal hydroxylase); Familial (X-linked ) hypophosphataemic rickets renal tubular defect in phosphate transport; Chronic renal disease; Fanconi syndrome (renal loss of phosphate) Target organ resistance to 1,25(OH)2D3- hereditary vitamin D-dependent rickets type II (due to mutations in vitamin D receptor gene).

15 Calcium regulation in the blood is as follows: Vitamin D2 in the food (exogenous) + vitamin D3 (skin, endogenous) =>liver microsomes =>25(OH) D3 => Mitochondrial kidney tubules membrane activated 3 forms: 24,25 (OH)2 D3; 1,24,25 (OH)2 D3; 1,25 (OH)2 D3!!! last more active. In placental macrophage of pregnancy women are present 1,25(OH)2 D3

16 FUNCTIONS OF VITAMIN D Intestine: Increases calcium binding protein Active transport in the jejunal cells Phosphorus ions absorption through specific phosphate carrier Alkaline phosphatase (AP) synthesis ATP-ase sensibility to calcium ions

17 BONES Mineralization of the bone and osteoblast differentiation Skeletal growth

18 KIDNEY Tubular re-absorption of calcium and phosphorus Produce 1,25(OH)2D3, the most active form

19 MUSCLES Increases the muscular protein and the ATP in myocytes Tonicity and the normal contraction of the muscles

20 PARATHYROID GLANDS Controls parathyroid hormone synthesis In case of low plasma calcium PTH secretion increases In response to secretion of PTH increase synthesis of 1,25(OH)2D3 PTH causes renal losses of phosphate, reducing the bone calcification Demineralization of bone level serum Ca increase to normal

21 OTHER EFFECTS OF VITAMIN D Cellular metabolism: citric acid oxidation Formation of soluble complex of citrate and Ca in the blood Skin differentiations in the local treatment of Psoriasis Pulmonary differentiation (Increases the surfactant in preterm infants) Immunomodulatory action in autoimmune disorders

22 SIGNS & SYMPTOMS Bony deformities Bowing of the legs (genuvarum, tibiae vara) Knock-knees (genuvalgum) Rachitic rosary costochondral junctions Swelling of the epiphysial growth plates Frontal bossing of the skull Pathological fractures. Poor growth Delayed dentition

23 Slow motor development. Muscle weakness. Extra skeletal (Tetany, Seizures, Laryngospasm, Hypocalcemic myocardiopathy, Death).

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29 CLINICAL MANIFESTATIONS Rickets may develop in any age of an infant, more frequent at 3-6mo, early in prematures. The first signs of hypocalcaemia are CNS changesexcitation, restlessness, excessive sweated during sleep and feeding, tremors of the chin and extremities. Skin and muscle changes- pallor, occipital alopecia, fragile nails and hair, muscular hypotony,motor retardation. Complications- apnoea, stridor, low calcium level with neuromuscular irritability (tetany). CNS changes are sometimes interpreted as CNS trauma and the administration of the Phenobarbital which activates the hepatic enzyme may deactivates vit.d and with in 1-2wk of the treatment with Phenobarbital the clinical stage worsens.

30 ACUTE SIGNS Have acute and subacute clinical signs Craniotabes acute sign of rickets, osteolyses detected by pressing firmly over the occipital or posterior parietal bones, ping-pong ball sensation will be felt. Large anterior fontanella, with hyperflexible borders, cranial deformation with asymmetric occipital flattening.

31 SUBACUTE SIGNS Subacute signs are all the following: frontal and temporal bossing False closure of sutures (increase protein matrix), in the X-ray craniostenosis is absent. Maxilla in the form of trapezium, abnormal dentition. Late dental evolution, enamel defects in the temporary and permanent dentition. Enlargement of costo-chondral junctions- rickets rosary Thorax, sternum deformation, softened lower rib cage at the site of attachment of the diaphragmharrison groove.

32 SUBACUTE SIGNS Spinal column- scoliosis, lordosis, kyphosis. Pelvis deformity, entrance is narrowed (add to cesarean section in females) Extremitiespalpated wrist expansion from rickets, tibia anterior convexity, bowlegs or knock kness legs. Deformities of the spine, pelvis and legs result in reduced stature, rachitic dwarfism. Delayed psychomotor development (heat holding, sitting, standing due to hypotonia).

33 VDDR TYPE I Corr Ca 2.02 mmol/l P 0.59 mmol/l ( ) ALP 3636 IU/l ( ) PTH 1087 pg/ml (10-60) 25(OH)D 31 ng/ml 1,25(OH)2D < 10 pg/ml (20-50) Known inactivating mutations in the CYP27B1 gene September month old child with severe Rickets

34 DIAGNOSIS Assessed according to the followings: 1. History 2. Physical examination 3. Laboratory findings 4. Roentgen-graphic changes

35 LABORATORY FINDINGS The most common laboratory findings in nutritional rickets are: Decreases in serum calcium, serum phosphorus, calcidiol, calcitriol, urinary calcium. Parathyroid hormone, alkaline phosphatase, urinary phosphorus levels are elevated.

36 Classic radiographic findings include: widening of the distal epyphysis, fraying and widening of the metaphysis, and angular deformities of the arm and leg bones. Anteroposterior and lateral radiographs of the wrist of an 8year-old boy with rickets demonstrates cupping and fraying of the metaphyseal region Radiographs of the knee of a 3-year-old girl with hypophosphatemia depict severe fraying of the metaphysis.

37 X-ray in rickets

38 COMPLICATIONS Rickets tetany Convulsions Respiratory disorders Cardiac disorders Skeletal deformation Frequent illness

39 DIFFERENTIAL DIAGNOSIS 1. Osteogenesis imperfecta, chondrodystrophy, congenital diseases- CMV, rubella, syphilis. 1. Chronic digestive and malabsorption disorders. 1. Hereditary Fanconi s disease, diabetes, renal tubular acidosis. phosphorus

40 TREATMENT 1. Special therapy: Vitamin D therapy General method: Vitamin D IU/day for 2-4 weeks, then change to preventive dosage 400 IU. A single large dose: For severe case, or Rickets with complication, or those who can t bear oral therapy. Vitamin D IU,, preventive dosage will be used after 2-3 months.

41 PROPHILAXIS IN RICKETS Specific antenatal prophylactic dose administration : IU/day of vitamin D3 solution at the 28-th week of pregnancy. The total dose administered is IU. In term infants prophylactic intake of vitamin D2 400IU/d started at 10 days of age during the first 2 years of life; in premature the dose may increase to 1000IU/day.

42 TREATMENT OF VITAMIN D DEFICIENCY Oral calcium supplements if necessary Monitoring: Improvement in symptoms (~ 2weeks) in serum PTH & alkaline phosphatase in serum phosphate, calcium & 25(OH)vitamin D Radiological healing (~ 3 months) Improvement of bow legs or knock-knees (~ 2 years. Provide vitamin D supplements (~ 400 iu/day) after the rickets has healed

43 4. Calcium supplementation: Dosage: 1-3 g/day only used for special cases, such as baby fed mainly with cereal or infants under 3 months of age and those who have already developed tetany. 5. Plastic therapy: In children with bone deformities after 4 years old plastic surgery may be useful.

44 VITAMIN D DEFICIENCY LONG TERM EFFECTS. Osteoporosis in later life. Cancer of the colon, prostate, breast, ovary, esophagus, etc. Autoimmune diseases like type 1 Diabetes Mellitus, Crohn s disease. Hypertension and heart diseases.

45 RADIOLOGICAL CHANGE Rx Vitamin D3 + Calcium

46 Rickets in wrist - uncalcified lower ends of bones are porous, ragged and saucer-shaped (A) Rickets in 3 month old infant (B) Healing after 28 days of treatment (C) After 41 days B C of treatment

47 THANKS FOR ATTENTION... ANY QUESTIONS??????