佝偻病手足抽搐症

1、BackgroundWhat happened to these children ?Mellanby Edward(1918)“ no more campaign on rickets” Rickets of vitamin D deficiency 营养性维生素D缺乏性佝偻病Teaching aimsDefinition What is Rickets?Mineralization:矿化 Osteoid:骨样组织 Osteomalacia:骨软化症 Rickets is the term signifying a failure in mineralization of growing b

2、one or osteoid tissue due to deficiency of vitamin DThe source and conversion of Vitamin DResource of VitD Calciferol(vitD2)Cholecalciferol(vitD3) 7-dehydrocholesterol in skin296310nmMaterno-fetus Dietary and therapeutic source Activation of VitDVitD2 VitD325(OH)D31,25(OH)2D3DBPHydrooxylated in the

3、renalHydrooxylated in the LiverCirculating formBiologically active formFunction of 1,25(OH)2D3Reabsorption of phosphorus in the kidneysDirect effect on mineral metabolism of boneAccommodation of cell proliferation and immune systemReceptors（intestins, renal, bone）Function of 1,25(OH)2D QuizTell us t

4、he function of 1,25(OH)2D3.What is the biologically active form of vitamin D? 25(OH) D3 What is the major circulating form of vitamin D ? 1,25(OH)2D3Antiricketic function：intestines, renal, boneOthers：anticancer，immunomodulationEtiologyetiology Disease Inadequate intake Rapid growth Inadequate expos

5、ure in sunlightVitD deficiency during perinatal period childrenVitD deficiency during perinatal period Whether all pregnancies should be given vitamin D need for a large placebo-controlled double-blind trial. (Cochrane collaboration)etiology Diseases Inadequate intake Rapid growth Inadequate exposur

6、e in sunlightVitD deficiency during perinatal period childrenSeasonsRegionsSkin colourslatitudesInadequate exposure in sunlight Spring AutumCity Countryside Black Asian WhiteHigher Loweretiology Disease Inadequate intake Rapid growth Inadequate exposure in sunlightVitD deficiency during perinatal pe

7、riod childrenRapid growth Multiple SinglePremature Full termetiology Diseases Inadequate intake Rapid growth Inadequate exposure in sunlightVitD deficiency during perinatal period childrenSupply calcium without VitDDelay auxiliary foods (辅食)Milk：25 IU/1LYolk：98IU/1gCalcium deficiency =Vitamin D defi

8、ciencyInadequate intake of Vit Detiology Diseases Inadequate intake Rapid growth Inadequate exposure in sunlightVitD deficiency during perinatal period childrenAntiseizure therapy抗癫痫治疗phenobarbitalCeliac diseaseCystic disease胆道疾病胃肠道疾病苯巴比妥Disease (chronic gastrointestinal diseases/ hepatic disease /

9、renal disease) Quiz What is the major cause of rickets ? Inadequate exposure in sunlightPathology骨的进一步生长软骨储备区软骨增生区软骨钙化区成骨区q 骺软骨不断生长并被骨组织替换。CalcifyCa*P 40钙盐沉着 35旧骨脱钙钙磷的作用33Decreased serumcalcium levelDeficiency of VitDLess calcium is absorbed from the intestineHypocalcemicParathormone（PTH）serumCa PMo

10、bilization of calcium and phosphorus from the bonekidney Decrease ph reabsorptionMaintain the serum calcium levelricketstetanyA failure in mineralization of growing bone or osteoid tissueMechanism 甲状旁腺素（PTH）341. osteoporosis occurs（骨膜增厚，骨质疏松软化）2. temporary calcification line lost normal shape or ext

11、inction （临时钙化带失去正常形态或消失）3. Osteoid tissue stacking（骨样组织堆积）4. Epiphyseal ribbon broader （干骺端变宽）Parathyriod glands甲状旁腺Tetany ofVitamin D deficiencyRickets ofvitamin D deficiencyVitamin D deficincy Quiz Calcium deficiency = Vitamin D deficiency? Quiz Clinical manifestations 8-month-old female child Exc

12、lusively breast-fed without vitamin supplement The mother did not receive any vitamins or calcium Presented with irritation and night sweating for 4 months Physical examination showed pulvinar bald(枕秃), cephalus quadratus（方颅）, without primary teeth erupion. Clinical diagnosis ?Rickets of vitamin D d

13、eficiency SummaryEarly stage Active rickets Healing ricketsSequela stage 3y Osseous changes + hypotonic + neural syndrome早期激期恢复期后遗症期411. Neurologic symptoms （sweating and irritation） 2. No osseous changes（骨骼无异常） craniotabes (颅骨软化)3. Serum calcium and phosphorus , 25(OH)VitD PTH AKP 4. X ray is norma

14、lEarly stage( 6m )Question 1 Why？ Sweating Irritation IrritationBone painnerve muscle excitability increasedhypocalcemiavitD deficiencyMechanism Question 2 Why is that?pulvinar bald（枕秃）night sweating（盗汗）451. Neurologic symptoms （sweating and irritation） 2. No osseous changes（骨骼无异常） craniotabes (颅骨软化

15、)3. Serum calcium and phosphorus , 25(OH)VitD PTH AKP 4. X ray is normalEarly stage( 1yr）Bowlegs (“O” 型腿)Knock-knees (“X”型腿)hypotony Crookback （驼背）Frog belly (蛙腹) 2010. 11LabsCalcium :2 (2.25 2.75mmol/L ) Phosphorus : 1 (1.3 2.3mmol/L) CaP: 35 (35 45mg/dL)PTH : 10 （110pmol/L）AKP: 240（50240U /L) X ra

16、y changesCalcium and phosphorus AKP PTH25(OH)VitD Craniotabes Pigeon breast Bowlegs and knock-kneesCephalus quadratusRachiticOsteoporosis Temporary calcification line extinction Osteoid tissue stacking Epiphyseal ribbon broaderSummary Sweating Irritation 57Healing rickets( 6m-2y )1. Clinical manifes

17、tations become invisible2. Serum biochemistry exams are becoming normal. 3. X rays are becoming normal 58Sequela stage( 3y )1. No clinical manifestations2. Normal serum Ca, P and AKP3. Normal X ray4. Skeletal deformities Quiz What are major clinical features of Rickets of VitD deficiency? 60 分期分期 初期

18、初期 激期激期 恢复期恢复期后遗症期后遗症期神经肌神经肌肉肉改变改变 夜啼夜啼 多汗多汗 激惹激惹 运动机能迟缓运动机能迟缓 肌张力低下肌张力低下 智力发育低下智力发育低下 好转好转 无无骨骼改骨骼改变变 无无 骨骼软化骨骼软化 骨样组织堆积骨样组织堆积 好转好转 畸形畸形生化生化检查检查 X X线线 PTH Ca P AKP 25(OH)D(-)(-) PTH Ca P AKP 25(OH)D (+) (+) 好转好转 好转好转 正常正常 正常正常 佝偻病各期临床表现DiagnosislaboratoryRadiographic examSerum levels of calcium and

19、 phosphorusElevated PTH and AKPUrinalysis, renal and liver function 。PrematurityMedical history (gestational age, diet, degree of sunlight exposure, family history, disease) Physical examinationclinicalDiagnosisSerum 25-(OH)D level is decreased(20ng/mL)*63Differential diagnosis64Differential diagnos

20、isRickets of anti VitD (抗维生素D佝偻病) 1. X-linked hypophosphatemic rickets(低血磷性抗维生素D佝偻病)2. renal tubule acidosis (远端肾小管性酸中毒)3. vitamin D-dependent rickets (VitD依赖性佝偻病)4. renal rickets (肾性佝偻病)5. liver rickets (肝性佝偻病)strongly s/o recent AsphyxiaMucopolysaccharidosis (粘多糖病)achondroplasia (软骨发育不全)Hydrocepha

21、lus (脑积水) s/o recent Asphyxia65 粘多糖病鉴别诊断66软骨发育不良鉴别诊断67脑积水Treatment Treatment sunlight exposure Calcium70objective: Control disease and prevent bone deformity.1. Natural and artificial sunlight exposure 2. Oral administration of VitDVitD2 2000-4000 IU/d 2-4w 400IU/dcalcifediol(2g/kg.d) calcitriol (0.

22、05 0.2g/kg.d) 3. Intramuscle injection of VitD2/3 VitD 30-60万IU 1-3 times4. Calcium 0.5-1.0g/d, 30 to 75 mg/kg.d (hungry bone)71Monitoring After treatment initiation, all patients will required careful monitoring.1. Serum ca, p and AKP, urinary ca/creatinine ratio and kidney function should be measu

23、re 4 weeks after the start of therapy. These tests should be repeated after 3 months.A rise in the level of phosphorus followed by calciumReappearance of urinary calcium excretion 2. Radiograhs should be obtained after 3 months of therapy.If the radiographs do not show evidence of healing, the possi

24、bility of poor adherence to treatment, malabsorption, or of other forms of rickets should be considered. 72Prevention1. Breast feeding2. Ensure adequate exposure to sunlight3. Vitamin D supplementation is recommended 400IU/dPremature neonate、multiple fetals、low birth weight infants：1 week after birt

25、h 800IU/d*3 mon400 IU/dFull term neonate：2weeks after birth 400IU/d*2 years old4. VitD for pregnant women73The American Academy of pediatrics(AAP) all breastfed infant and bottlefed infants (receiving less than 500ml formula daily) should receive 200 IU vitamin D daily.74 Tetany of vitamin D deficie

26、ncy 维生素D缺乏性手足搐搦症75General consideration 76General consideration Tetany of vitamin D deficiency occurs most frequently under the ages of 6 month. Tetany is rare today owing to widespread prophylactic use of vitamin D. Tetany is occasionally associated with celiac disease, such as diarrhea. 77 Definit

27、ion VitD deficiency causes hypocalcemia directly increases peripheral neuromuscular irritability, which can cause convulsion or local muscle tic 78Pathology 79结合钙-Constructing of bone 99% 游离钙 -Accommadation in cell excretion, signal entrainment, stimulated nerve muscle convection, blood clotting, an

28、d blood oxygen trafficBiologic function of Ca80Serum CaAccommodation of Ca l 1,25（OH）2D3、PTH、CT PH Plasma protein concentration Plasma phosphorus concentration The compose of Serum Ca (1%) ionic Ca （47%）: physioactivity protein binding Ca （47%）: unactivity compound （6%）: binding with organic acid an

29、d inorganic acid,unactivity81hypocalcemiaDeficiency of VitDLess calcium is absorbed from the intestinehypocalcemiaParathormone（PTH）100NoserumCa P*Mobilization of calcium and phosphorus from the bonekidney Decrease ph reabsorptionMaintain the serum calcium levelricketstetanyA failure in mineralizatio

30、n of growing bone or osteoid tissueMechanism 82Clinical manifestations83Clinical manifestationsLatent tetany No symptoms Positive signs Chvostek Trousseau serum calcium lever is less than 1.75-1.88mmol/LManifest tetanyLaryngospasm Carpopedal spasmConvulsionsSerum calcium lever is is often well under

31、 1.75mmol/L84Figure: Carpopedal spasm85diagnosis 86diagnosis History- age, season, history of VD dificiency, symptoms and signs of ricketsClinical manifestations - convulsion without fever, repeat occurs, consciouse after seizures without CNS signsTotal Ca - 1.75-1.88mmol/L, ionic Ca1.0mmol/L。 87Differential diagnosisConvulsion without fever hypomagnesemia Hypoparathyroidism H