V.N. V.N. Karazin Karazin Kharkiv Kharkiv National National UniversityUniversity

The The Department Department of Pediatricsof Pediatrics

RICKETSRICKETS

Assistant of the Department of PediatricsAssistant of the Department of PediatricsLyudmyla OlexandrivnaLyudmyla Olexandrivna RakovskaRakovska

The plan of the lecture:The plan of the lecture:1. Definition and types of Rickets2. Metabolism of Vitamin D, Ca, and P3. Etiology of Rickets4. Pathogenesis of Rickets5. Classification of Rickets6. Clinical manifestations of Rickets 7. Laboratory and radiological findings8. Differential diagnosis9. Treatment and Prevention of Rickets10. Hypervitaminosis D: pathogenesis,

clinical features, diagnosis, differential diagnosis, treatment

Rickets (Rickets (RachitisRachitis))

is a metabolic disease of is a metabolic disease of growing bone that is unique growing bone that is unique to children (especially of first to children (especially of first 2 years) and adolescents. It 2 years) and adolescents. It is caused by a failure of is caused by a failure of osteoid to calcify in a growing osteoid to calcify in a growing person. person.

RicketsRickets characterized by a failure of characterized by a failure of

bone tissue to be properly bone tissue to be properly mineralized, especially by mineralized, especially by imperfect calcification, typically imperfect calcification, typically resulting in soft bones and resulting in soft bones and skeletal deformities.skeletal deformities.

““English disease” is another English disease” is another name of Ricketsname of Rickets

old English old English word word wrickwrick, , ((wrickkenwrickken) ) means "to twist”. means "to twist”.

The Greek word The Greek word "rachitis" "rachitis" (ῥαχίτης, (ῥαχίτης, meaning “to meaning “to bend”bend”

Types of Types of RicketsRickets Nutritional Rickets or vitamin Nutritional Rickets or vitamin

D-deficiency RicketsD-deficiency Rickets Vitamin D-dependent RicketsVitamin D-dependent Rickets

• Type IType I• Type IIType II

Vitamin D-resistant Rickets Vitamin D-resistant Rickets (“looks like Rickets”)(“looks like Rickets”)

Secondary Secondary RicketsRickets

ETIOLOGYETIOLOGY

Main cause of Rickets is Main cause of Rickets is vitamin D deficiencyvitamin D deficiency

VITAMINVITAMIN

Vitamin D is a Vitamin D is a fat-soluble fat-soluble vitamin. It is vitamin. It is often called often called the "sunshine" the "sunshine" vitaminvitamin

calcium homeostasiscalcium homeostasis

absorption of Ca and P absorption of Ca and P in the small intestinein the small intestine

Role of vitamin DRole of vitamin DRole of vitamin DRole of vitamin D

normal mineralization of normal mineralization of bonebone

reabsorption Ca and P reabsorption Ca and P in the renal tubulein the renal tubule

Vitamin DVitamin D

D2D2ergocalciferolergocalciferol

D3D3cholecalciferolcholecalciferol

Vitamin D Metabolism

(Adapted from Lucas et al.) Taylor S N et al. Neoreviews 2009;10:e590-e599 ©2009 by American Academy of Pediatrics

Pathophysiology Pathophysiology

Vitamin D and HealthVitamin D and Health

Results of vitamin D deficiency:Results of vitamin D deficiency: rickets in childrenrickets in children osteomalacia in adultsosteomalacia in adults fractures in adults and older adultsfractures in adults and older adults cancers (breast, prostate, colon)cancers (breast, prostate, colon) autoimmune diseasesautoimmune diseases infectious diseasesinfectious diseases type I diabetes mellitus and othertype I diabetes mellitus and other

PATHOGENESIS PATHOGENESIS Causes of vitamin D deficiencyCauses of vitamin D deficiency

1. 1. Disorders associated with Vitamin D Disorders associated with Vitamin D synthesissynthesis

• Deficiency in cutaneously synthesized Deficiency in cutaneously synthesized vitamin D vitamin D

• Lack of dietary intakeLack of dietary intake

2. 2. Disorders associated with Vitamin D Disorders associated with Vitamin D absorbtionabsorbtion

3. 3. Chronic diseases Chronic diseases of theof the liver liver oror kidney kidney

4. 4. Hereditary (congenital) anomalies Hereditary (congenital) anomalies of metabolism of Vitamin D, Ca, P.of metabolism of Vitamin D, Ca, P.

Sun ExposureSun Exposure

20 to 30 minutes 20 to 30 minutes of sun of sun (especially (especially between the between the hours of 10:00 hours of 10:00 am and 3:00 am and 3:00 pm)pm) three or three or four times a four times a week ensure week ensure enough vitamin enough vitamin D in peopleD in people..

Causes of vitamin D deficiency Causes of vitamin D deficiency cutaneously synthesizedcutaneously synthesized

Cancer???

Lack of Lack of dietary Intakedietary Intake

Vitamin D malabsorption Vitamin D malabsorption problemsproblems

celiac sprue, celiac sprue, short bowel syndrome, short bowel syndrome,  cystic fibrosiscystic fibrosis

Medications are associated Medications are associated with vitamin D deficiencywith vitamin D deficiency

SteroidsSteroids Antiepileptic (anticonvulsants) drugs:Antiepileptic (anticonvulsants) drugs:PhenobarbitalPhenobarbital and and PhenytoinPhenytoin

(brand name Dilantin®)(brand name Dilantin®) OrlistatOrlistat (brand names Xenical® and (brand names Xenical® and

alliTM) and the cholesterol-lowering alliTM) and the cholesterol-lowering drug drug CholestyramineCholestyramine (brand names (brand names Questran®, LoCholest®, and Questran®, LoCholest®, and Prevalite®)Prevalite®)

Secondary Secondary RicketsRickets

Chronic liver diseasesChronic liver diseases End-stage renal diseases (renal End-stage renal diseases (renal

osteodystrophy)osteodystrophy)

Hereditary (congenital) Hereditary (congenital) anomalies of metabolism of anomalies of metabolism of

Vitamin D, Ca and PVitamin D, Ca and P Vit D-dependent rickets of I typeVit D-dependent rickets of I type

(pseudovitamin D-deficiency rickets)(pseudovitamin D-deficiency rickets) - defect - defect in the gene coding of renal 1-alpha-hydroxylase. in the gene coding of renal 1-alpha-hydroxylase. Autosomal recessive desease.Autosomal recessive desease.

Vit D-dependent rickets of II typeVit D-dependent rickets of II type (hereditary 1-alfa, 25-dihydroxyvitamin D-(hereditary 1-alfa, 25-dihydroxyvitamin D-resistent rickets)resistent rickets) - mutation exists in the - mutation exists in the vitamin D receptors (VDR). Autosomal recessive vitamin D receptors (VDR). Autosomal recessive desease.desease.

Vit D-resistent ricketsVit D-resistent rickets (familial (familial hypophosphatemic rickets)hypophosphatemic rickets) - mutations of the - mutations of the phosphate-regulating gene on the X chromosomephosphate-regulating gene on the X chromosome

Classification of RicketsClassification of Rickets

Degree Period of disease Course

Mild (I)Moderate(II)Severe(III)

Initial Height (manifest) (“Florid rickets”)Reconvalescenction (reparation)Residual symptoms (permanent changes)

Acute

Subacute

Recurring

CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONS

I. Findings I. Findings specificspecific to the bone to the bone tissue in ricketstissue in rickets

Symptoms of osteomalacia:Symptoms of osteomalacia: Symptoms of hyperplasia of Symptoms of hyperplasia of

osteoid tissueosteoid tissue Symptoms of hypoplasia of Symptoms of hypoplasia of

osseous tissueosseous tissueII. Findings II. Findings not specificnot specific to the to the

bone tissue in ricketsbone tissue in rickets

Findings Findings specificspecific to the bone tissue to the bone tissue

Symptoms of osteomalacia:Symptoms of osteomalacia:

ссraniotabesraniotabes softening of the big fontanel's softening of the big fontanel's

edgesedges softening of ribs softening of ribs kyphosiskyphosis bowing in the legs bowing in the legs

Findings Findings specificspecific to the bone tissue to the bone tissue Symptoms of hyperplasia of Symptoms of hyperplasia of

osteoid tissue:osteoid tissue:

increase of frontal and occipital increase of frontal and occipital tubers (frontal bossing, “caput tubers (frontal bossing, “caput quadratum”)quadratum”)

costohondral prominence ("rachitic costohondral prominence ("rachitic rosary")rosary")

chest deformities (Harrison’s groove chest deformities (Harrison’s groove and pigeon breast)and pigeon breast)

Findings Findings specificspecific to the bone tissue to the bone tissue Symptoms of hypoplasia of Symptoms of hypoplasia of

osseous tissue:osseous tissue:

delayed fontanel closure delayed fontanel closure delayed teethingdelayed teething enamel hypoplasiaenamel hypoplasia costal or lower extremity fractures costal or lower extremity fractures

(particularly greenstick fractures)(particularly greenstick fractures) lag of growth of tubular bones in lag of growth of tubular bones in

length in severe cases.length in severe cases.

Findings not specific to the Findings not specific to the bone tissue in rickets:bone tissue in rickets:

occipital alopecia occipital alopecia muscular hypotonia muscular hypotonia constipation,constipation, hypocalcemic convulsions,hypocalcemic convulsions, anemia, anemia, increased risk for respiratory infections.increased risk for respiratory infections. growth retardation and low growth retardation and low

height−for−age (rachitic dwarfism).height−for−age (rachitic dwarfism).

In acute course of rickets symptoms of In acute course of rickets symptoms of osteomalacia prevail, in subacute – osteomalacia prevail, in subacute – symptoms of hyperplasia of osteoid tissue. symptoms of hyperplasia of osteoid tissue. Skeletal deformities become obvious in Skeletal deformities become obvious in stage II and worsen in stage III. stage II and worsen in stage III.

Initial period is starting from 2-3 month of Initial period is starting from 2-3 month of life, lasts from 2-3 weeks to 2-3 months. In life, lasts from 2-3 weeks to 2-3 months. In breast-fed infants whose mothers have breast-fed infants whose mothers have osteomalacia, rickets may develop before osteomalacia, rickets may develop before 2 mo. 2 mo.

Florid rickets appears toward the end of Florid rickets appears toward the end of the 1st and during the 2nd year of life. the 1st and during the 2nd year of life. Later in childhood, manifest vitamin D Later in childhood, manifest vitamin D deficient rickets is rare. deficient rickets is rare.

PHYSICAL EXAMINATION: HeadPHYSICAL EXAMINATION: Head Craniotabes Craniotabes (areas (areas

of thinning and of thinning and softening of bones of softening of bones of the skull) manifests the skull) manifests early in infants older early in infants older than 2−3 months. than 2−3 months.

It detected by pressing It detected by pressing firmly over the firmly over the occiput or posterior occiput or posterior parietal bones. A parietal bones. A ping-pong-ball ping-pong-ball sensation will be felt.sensation will be felt.

PHYSICAL EXAMINATION:PHYSICAL EXAMINATION: Head Head

frontal bossing which give the head a frontal bossing which give the head a boxlike or boxlike or "square headed""square headed" appearance appearance (caput quadratum)(caput quadratum)

PHYSICAL EXAMINATION:PHYSICAL EXAMINATION: ChestChest

knobby knobby deformities deformities ««rachitic rosaryrachitic rosary»» ( (“rosary beads”) “rosary beads”) along the along the costochondral costochondral junctionsjunctions

PHYSICAL EXAMINATION:PHYSICAL EXAMINATION: ChestChestThe weakened ribs pulled by muscles also The weakened ribs pulled by muscles also

produce flaring over the diaphragm, which produce flaring over the diaphragm, which is known as is known as Harrison grooveHarrison groove..

PHYSICAL EXAMINATION:PHYSICAL EXAMINATION: ChestChest

pigeon-breast pigeon-breast deformitydeformity

PHYSICAL EXAMINATION:PHYSICAL EXAMINATION: ExtremitiesExtremities

enlargement thickening of the wrists enlargement thickening of the wrists

PHYSICAL EXAMINATION:PHYSICAL EXAMINATION: ExtremitiesExtremities

enlargement enlargement thickening of the thickening of the anklesankles

Вowing in the legsВowing in the legs

Genu varumGenu varum

bowlegs or “O“−type leg deformity bowlegs or “O“−type leg deformity occurs when the femoral occurs when the femoral intercondylar distance exceeds 5 cm intercondylar distance exceeds 5 cm

Genu varumGenu varum

Genu valgumGenu valgum

knock-knees or knock-knees or “X“−type leg “X“−type leg deformitydeformity

PHYSICAL EXAMINATION:PHYSICAL EXAMINATION: SpineSpine

kyphoskyphos

PHYSICAL EXAMINATION:PHYSICAL EXAMINATION: non specific symptomsnon specific symptoms

Muscular hypotoniaMuscular hypotonia Generalized muscular hypotoniaGeneralized muscular hypotonia "floppy baby syndrome" or "slinky "floppy baby syndrome" or "slinky

baby" (such that the baby is floppy baby" (such that the baby is floppy or slinky-like)or slinky-like)

PHYSICAL EXAMINATION:PHYSICAL EXAMINATION: non specific symptomsnon specific symptoms

Neurologic abnormalitiesNeurologic abnormalities observed in all cases and revealed at observed in all cases and revealed at

initial period of disease as irritability, initial period of disease as irritability, interrupted sleep, sweating. interrupted sleep, sweating.

PHYSICAL EXAMINATION:PHYSICAL EXAMINATION: non specific symptomsnon specific symptoms

Occipital alopeciaOccipital alopecia Increased sweating, particularly Increased sweating, particularly

around the head, may also be around the head, may also be present as non specific symptom. It present as non specific symptom. It leads to occipital alopecia and occurs leads to occipital alopecia and occurs in 30%.in 30%.

rachitic rosary (62.1%), rachitic rosary (62.1%), craniotabes (49%), occipital craniotabes (49%), occipital alopecia (31.4%) and alopecia (31.4%) and enlargement of the wrists enlargement of the wrists (27.1%) were the four most (27.1%) were the four most common physical examination common physical examination findings for the age group 0−6 findings for the age group 0−6 monthsmonths

TETANY (SPASMOPHILIA)TETANY (SPASMOPHILIA)

disease of infants, resultdisease of infants, resultinging from from disturbances of disturbances of CaCa metabolism and metabolism and characterized characterized by the by the development of development of tonetic and tonoclonic tonetic and tonoclonic convulsions. convulsions.

Most frequent symptoms and Most frequent symptoms and signs of latent Tetanysigns of latent Tetany

Chvostek’s sign;Chvostek’s sign; Trousseau’s symptom;Trousseau’s symptom; Maslov’s symptom;Maslov’s symptom; Erb’s symptomErb’s symptom;; Lust’s signLust’s sign

Most frequent symptoms and Most frequent symptoms and signs of Manifestsigns of Manifest TetanyTetany

LaryngospasmLaryngospasm Carpopedal spasmCarpopedal spasm General tonic convulsionsGeneral tonic convulsions

Convulsive spasm of a heart Convulsive spasm of a heart muscle leading to child’s death is muscle leading to child’s death is possiblepossible!!!!!!

In a patient suspected to have In a patient suspected to have rickets based on clinical findings, rickets based on clinical findings, the diagnosis is confirmed by the diagnosis is confirmed by biochemical and radiological biochemical and radiological findingsfindings. . 

LABORATORY FINDINGSLABORATORY FINDINGS

Obligatory Obligatory serum measurementsserum measurements :: Calcium Calcium PhosphorusPhosphorus ((N)N) Alkaline phosphataseAlkaline phosphatase (N) (N)

Additional:Additional: 25-hydroxy vitamin D25-hydroxy vitamin D Parathyroid hormoneParathyroid hormone Sulkovich’s test of urineSulkovich’s test of urine

Calcidiol Calcidiol PTHPTH

(25-hydroxy (25-hydroxy

vitamin D)vitamin D)

Serum 25(OH)D (calcidiol)Serum 25(OH)D (calcidiol)

vitamin Dvitamin D -- NormalNormal potentialpotentialdeficiency-insufficiecydeficiency-insufficiecy adverseadverse

effectseffects

00 2525 5050 7575 125 125 nmol/L

** 1 nmol/L = 0.4 ng/mL** 1 nmol/L = 0.4 ng/mL

≥50 nmol/L (≥20 ng/mL)

>125 nmol/L (>50 ng/mL)

Sulkovich’s testSulkovich’s test

This test gives approximate This test gives approximate presentation about Ca content in presentation about Ca content in blood from is presents in urine.blood from is presents in urine.

Assessment of result:Assessment of result:

““+” – normal level+” – normal level

““++, ++++” – hypercalcaemia and ++, ++++” – hypercalcaemia and hypercalciuria hypercalciuria

RADIOLOGICAL FINDINGSRADIOLOGICAL FINDINGS

RADIOLOGICAL FINDINGSRADIOLOGICAL FINDINGS

Rickets leads to Rickets leads to cupping and to a cupping and to a brush−like brush−like appearance of the appearance of the epiphyseal ends on epiphyseal ends on radiograms.radiograms.

Radiographs of the Radiographs of the knee of a 3.6-year-knee of a 3.6-year-old girl with old girl with hypophosphatemia hypophosphatemia depict severe depict severe fraying of the fraying of the metaphysis.metaphysis.

N Active Rickets recovery

RADIOLOGICAL FINDINGSRADIOLOGICAL FINDINGS

Anteroposterior and lateral radiographs of Anteroposterior and lateral radiographs of the wrist demonstrates cupping and the wrist demonstrates cupping and fraying of the metaphyseal region.fraying of the metaphyseal region.

RADIOLOGICAL FINDINGSRADIOLOGICAL FINDINGS

Rosary beads of Rosary beads of ricketsrickets

curved backcurved back

DIFFERENTIAL DIAGNOSISDIFFERENTIAL DIAGNOSIS Vitamin D [ deficient ricketsVitamin D [ deficient rickets Vitamin D [ dependent rickets (types I and II)Vitamin D [ dependent rickets (types I and II) Vitamin D-resistent Rickets (“looks like Rickets”):Vitamin D-resistent Rickets (“looks like Rickets”):

• Hereditary X-linked hypophosphatemic rickets with Hereditary X-linked hypophosphatemic rickets with hypocalciuriahypocalciuria

• Familial hypophosphatrmicFamilial hypophosphatrmic• Phosphat-diabetesPhosphat-diabetes• Achondrodroplasia Achondrodroplasia • Fanconi syndrome (De Toni-Debre-Fanconi desease) (types I Fanconi syndrome (De Toni-Debre-Fanconi desease) (types I

and II)and II) PseudohypoparathyroidismPseudohypoparathyroidism Renal tubular acidosisRenal tubular acidosis CystinosisCystinosis TyrosinemiaTyrosinemia Secondary Secondary Rickets (renal, gastrointestinal, tumor-Rickets (renal, gastrointestinal, tumor-

associated, medications, malabsortion syndromes et associated, medications, malabsortion syndromes et all)all)

Familial Familial hypophosphatemichypophosphatemicLow stature in the Low stature in the

family, dental family, dental deformities, deformities, orthopaedic orthopaedic abnormalities, and abnormalities, and consanguineous consanguineous marriage indicated marriage indicated for hereditary for hereditary hypophosphatemic hypophosphatemic rickets rickets

Renal osteodystrofyRenal osteodystrofy

Chronic renal Chronic renal failure IV st, failure IV st, prolonged of prolonged of haemodyalishaemodyalis

AchondrodroplasiaAchondrodroplasia

Differential diagnosis tetanyDifferential diagnosis tetany

includesincludes hyperthermic convulsions, hyperthermic convulsions, complicated pneumonia, meningitis, complicated pneumonia, meningitis, viral diseases. In hypoparathyroidism viral diseases. In hypoparathyroidism which is very rare in babies, which is very rare in babies, hypocalcemia and hypocalcemia and hyperphosphatemia are usual. hyperphosphatemia are usual. Eclamptic form is necessary to Eclamptic form is necessary to differentiate from epilepsy.differentiate from epilepsy.

TREATMENTTREATMENT

Common measures Common measures in rickets in rickets treatment treatment irrespective of its irrespective of its form are the form are the following:following:

adequate feeding, adequate feeding, regimen and walks;regimen and walks;

massage and massage and physical trainingphysical training

It is marketed under various names It is marketed under various names including Deltalin (Eli Lilly and Company), including Deltalin (Eli Lilly and Company), Drisdol (Sanofi-Synthelabo) and Calcidol Drisdol (Sanofi-Synthelabo) and Calcidol (Patrin Pharma).(Patrin Pharma).

Ergocalciferol is a form of Ergocalciferol is a form of vitamin D, also called vitamin D2.vitamin D, also called vitamin D2.

Cholecalciferol is a form of vitamin Cholecalciferol is a form of vitamin D, also called vitamin D3 D, also called vitamin D3 or calciolor calciol

1. Low dosage 1. Low dosage andand long−term long−term vitamin D therapy vitamin D therapy ((gradual method)gradual method)

1000− 10 000 IU/day (125-250 mcg) for 2−3 1000− 10 000 IU/day (125-250 mcg) for 2−3 monthsmonths

Vitamin D can be given according to the Vitamin D can be given according to the infant’s age as follows: infant’s age as follows:

1000 IU/day for infants <1000 IU/day for infants < 1 month of age, 1 month of age, 1000-5000 IU/ day for children 1-12 mon1000-5000 IU/ day for children 1-12 mon.. 5000-10 000 IU/day for children >5000-10 000 IU/day for children > 12 mon.12 mon. If hypocalcemia is seen the initial dose of vit If hypocalcemia is seen the initial dose of vit

D must be doubled.D must be doubled. Afterwards, it is recommended to give Afterwards, it is recommended to give

maintenance therapy of 400 IU/ day. maintenance therapy of 400 IU/ day.

Because this method requires daily Because this method requires daily treatment, success depends on treatment, success depends on compliance.compliance.

Levels of Ca and P are normalized in 6−10 Levels of Ca and P are normalized in 6−10 days by this therapy, while it takes 1−2 days by this therapy, while it takes 1−2 months for PTH to reach normal levels. months for PTH to reach normal levels. Depending on the severity of the disease, Depending on the severity of the disease, it may take 3 months for the normal serum it may take 3 months for the normal serum ALP levels to be restored and the ALP levels to be restored and the radiological findings of rickets to radiological findings of rickets to disappear. disappear.

In this treatment model, lack of In this treatment model, lack of compliance is an important cause of lack compliance is an important cause of lack of responseof response

2. Stoss therapy 2. Stoss therapy ((single-day therapy)single-day therapy)

For patients who are suspected to For patients who are suspected to have poor compliance, a high dose of have poor compliance, a high dose of vitamin D can be given orally or vitamin D can be given orally or intramuscularly as a single dose of intramuscularly as a single dose of 100 000−600 000 IU after the first 100 000−600 000 IU after the first month of life.month of life.

This dose is usually divided into 4 or This dose is usually divided into 4 or 6 oral doses. An intramuscular 6 oral doses. An intramuscular injection is also available.injection is also available.

Stoss therapy Stoss therapy ((single-day therapy)single-day therapy)

Administration of 150 000−300 000 units Administration of 150 000−300 000 units of vitamin D and 600 000 units (15,000 of vitamin D and 600 000 units (15,000 mcg) in severe rickets is an effective and mcg) in severe rickets is an effective and safe method of treatment.safe method of treatment.

Vitamin D (cholecalciferol) is well stored Vitamin D (cholecalciferol) is well stored in the body and is gradually released over in the body and is gradually released over many weeks. This treatment evokes a many weeks. This treatment evokes a rapid clinical response, resulting in rapid clinical response, resulting in biochemical recovery in a few days and biochemical recovery in a few days and radiological recovery in 10−15 days.radiological recovery in 10−15 days.

The single-day therapy avoids The single-day therapy avoids problems with compliance and may problems with compliance and may be helpful in differentiating be helpful in differentiating nutritional rickets from familial nutritional rickets from familial hypophosphatemia rickets (FHR). In hypophosphatemia rickets (FHR). In nutritional rickets, the phosphorus nutritional rickets, the phosphorus level rises in 96 hours and level rises in 96 hours and radiographic healing is visible in 6-7 radiographic healing is visible in 6-7 days. Neither happens with FHR.days. Neither happens with FHR.

Ca therapyCa therapy Ca administration Ca administration

becomes becomes necessary when necessary when clinical signs of clinical signs of tetany or tetany or convulsions are convulsions are present. present.

Emergency care of tetanyEmergency care of tetany 10% Ca gluconate (1−2 ml/kg, or 0,3-0,5 10% Ca gluconate (1−2 ml/kg, or 0,3-0,5

mg\kg 3 times a day) IV and slowly while mg\kg 3 times a day) IV and slowly while monitoring ECG (bradicardia, arrhythmia).monitoring ECG (bradicardia, arrhythmia).

In convulsions it is necessary to inject i.v. In convulsions it is necessary to inject i.v. seduxen (0.1 ml/kg or 0,5 mg\kg of 0,5% seduxen (0.1 ml/kg or 0,5 mg\kg of 0,5% solution), MgSO4 (0,2-0.5 ml/kg of 25% solution), MgSO4 (0,2-0.5 ml/kg of 25% solution), sodium oxybutirate (0.5 ml/kg or solution), sodium oxybutirate (0.5 ml/kg or 50-120 mg\kg of 20% solution), oxygen 50-120 mg\kg of 20% solution), oxygen inhalations. inhalations.

In laryngospasm it is necessary to create a In laryngospasm it is necessary to create a dominant focus of excitement in the brain dominant focus of excitement in the brain (irritation of nasal mucosa, skin with a (irritation of nasal mucosa, skin with a prick, tap). prick, tap).

Ca levels should then be maintained Ca levels should then be maintained with oral Ca supplements.with oral Ca supplements.

Infants with latent tetany may Infants with latent tetany may respond orally calcium gluconate respond orally calcium gluconate (5%) or calcium chloride (1-2%) – 1 (5%) or calcium chloride (1-2%) – 1 teaspoonful x 3 times a day.teaspoonful x 3 times a day.

Restriction of cow milk because of Restriction of cow milk because of great quantity of phosphates.great quantity of phosphates.

After 3-4 days – vit D 2-4 000 twice a After 3-4 days – vit D 2-4 000 twice a day is prescribed.day is prescribed.

Orthopedic correctionOrthopedic correction

If severe If severe deformities have deformities have occurred, occurred, orthopedic orthopedic correction may be correction may be required after required after healing. Most of healing. Most of the deformities the deformities correct with correct with growth.growth.

Pharmacologic Therapy Pharmacologic Therapy of D 3 resistant ricketsof D 3 resistant rickets

familial hypophosphatemic ricketsfamilial hypophosphatemic rickets The usual vitamin D preparations are not The usual vitamin D preparations are not

useful for treatment in this disorder, useful for treatment in this disorder, because they lack significant 1-alpha-because they lack significant 1-alpha-hydroxylase activity. Original treatment hydroxylase activity. Original treatment protocols advocated vitamin D at levels of protocols advocated vitamin D at levels of 25,000-50,000 U/d (at the lower limit of 25,000-50,000 U/d (at the lower limit of toxic dosage). Amiloride and toxic dosage). Amiloride and hydrochlorothiazide are administered to hydrochlorothiazide are administered to enhance calcium reabsorption and to enhance calcium reabsorption and to reduce the risk of nephrocalcinosis.reduce the risk of nephrocalcinosis.

Result of treatment Result of treatment of familial of familial hypophosphatemic ricketshypophosphatemic rickets

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PREVENTIONPREVENTION

AntenatalAntenatal PostnataPostnata

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Physiological method to prevent Physiological method to prevent vitamin D insufficiency/deficiencyvitamin D insufficiency/deficiency

To educate society, sufficiently To educate society, sufficiently exposed to sunlight mothers and exposed to sunlight mothers and infants and rational feeding infants and rational feeding (balanced diet rich in Ca and vitamin (balanced diet rich in Ca and vitamin D), individual care, gymnastics, D), individual care, gymnastics, massage.massage.

Dietary IntakeDietary Intake

Natural nutritional Natural nutritional sources of vitamin D are sources of vitamin D are limited primarily to limited primarily to fatty, ocean-going fish.fatty, ocean-going fish.

The fortification of milk The fortification of milk with vitamin D with vitamin D beginning in the 1930s beginning in the 1930s has made rickets a rare has made rickets a rare disease in the United disease in the United States. Thus, the States. Thus, the disorder is rarely seen disorder is rarely seen today in countries today in countries where "fortified" milk is where "fortified" milk is available.available.

Specific methods of prevent of Specific methods of prevent of vitamin D-deficiency Ricketsvitamin D-deficiency Rickets (VDR)(VDR)

Supplementation vitamin D Supplementation vitamin D for mother and child.for mother and child.

Today, vitamin D Today, vitamin D prophylaxis means not only prophylaxis means not only prevention of clinical prevention of clinical rickets (VDD) but also rickets (VDD) but also maintenance of optimal maintenance of optimal serum 25 (OH)D level in serum 25 (OH)D level in order to prevent vitamin D order to prevent vitamin D insufficiency. insufficiency.

The daily maintenance dose of The daily maintenance dose of vitamin D varies by age. It has been vitamin D varies by age. It has been reported that the dose of reported that the dose of prophylactic vitamin D should be prophylactic vitamin D should be between 400 and 1000 IU/day to between 400 and 1000 IU/day to maintain the serum 25(OH)D at maintain the serum 25(OH)D at optimum levels (50-75 nmol/L).optimum levels (50-75 nmol/L).

The The 20032003 American Academy of American Academy of Pediatrics (AAP) vitamin D guidelines Pediatrics (AAP) vitamin D guidelines recommended a minimal vitamin D dose recommended a minimal vitamin D dose of 200 IU/day due to evidence of 200 IU/day due to evidence demonstrating that this dose would demonstrating that this dose would maintain serum 25(OH)D concentrations maintain serum 25(OH)D concentrations greater than greater than 27.5 nmol/L27.5 nmol/L. .

The The 20082008 AAP guidelines recommend an AAP guidelines recommend an increased minimum supplementation of increased minimum supplementation of 400 IU/day to ensure serum 25(OH)D 400 IU/day to ensure serum 25(OH)D values greater than values greater than 50 nmol/L50 nmol/L to avoid to avoid vitamin D-deficient rickets. AAP report vitamin D-deficient rickets. AAP report recommends 400 IU/day for all infants, recommends 400 IU/day for all infants, children, and adolescents, with initiation of children, and adolescents, with initiation of the supplementation in the “first few days” the supplementation in the “first few days” after birth.after birth.

The Endocrine Society The Endocrine Society recommends (2011) :recommends (2011) :

The Endocrine Society, along with the Canadian Society The Endocrine Society, along with the Canadian Society of Endocrinology and Metabolism and the National of Endocrinology and Metabolism and the National Osteoporosis Foundation, published a clinical practice Osteoporosis Foundation, published a clinical practice guideline in 2011 titled "Evaluation, Treatment and guideline in 2011 titled "Evaluation, Treatment and Prevention of Vitamin D Deficiency."Prevention of Vitamin D Deficiency."

400 IU (10 mcg) for children aged 0-1 year400 IU (10 mcg) for children aged 0-1 year 600 IU/day (15 mcg) for children aged 1-18 600 IU/day (15 mcg) for children aged 1-18

years years 1500-2000 IU for all men and women older 1500-2000 IU for all men and women older

than 18 years, including lactating and than 18 years, including lactating and pregnant women whose infants are not pregnant women whose infants are not ingesting vitamin D. ingesting vitamin D.

Also with a perspective to prevent Also with a perspective to prevent early rickets, it is recommended that early rickets, it is recommended that vitamin D at a dose of 2000 IU/day vitamin D at a dose of 2000 IU/day should be administered during the should be administered during the last trimester of pregnancy to last trimester of pregnancy to mothers with poor exposure to mothers with poor exposure to sunlight due to various reasons and sunlight due to various reasons and who are at high risk of Vitamin D who are at high risk of Vitamin D deficiency. deficiency.

Ergocalciferol and Ergocalciferol and Cholecalciferol are used for Cholecalciferol are used for specific prevent of rickets. Use of specific prevent of rickets. Use of total 2-5 daily doses in one total 2-5 daily doses in one intake (correspondingly every 2-5 intake (correspondingly every 2-5 days).days).

Prophylactic course of vitamin D Prophylactic course of vitamin D may be interrupted by UV may be interrupted by UV irradiation. irradiation.

Specific prevention isn’t carried Specific prevention isn’t carried out in the children receiving out in the children receiving formula feeding.formula feeding.

Families with inherited rickets may Families with inherited rickets may seek genetic counseling.seek genetic counseling.

HYPERVITAMINOSIS DHYPERVITAMINOSIS D

Hypervitaminosis D is a condition Hypervitaminosis D is a condition result from toxic action of vitamin D result from toxic action of vitamin D and is characterized with intoxication and is characterized with intoxication of different degree, affection of of different degree, affection of organs and systems and organs and systems and development of hypercalcemiadevelopment of hypercalcemia..

HYPERVITAMINOSIS DHYPERVITAMINOSIS D

10,000 - 40,000 IU/day

PathogenesisPathogenesis

direct toxic action upon cellular direct toxic action upon cellular membranes, metabolism, and membranes, metabolism, and consequences of hypercalcemia. consequences of hypercalcemia.

Classification of Classification of Hypervitaminosis DHypervitaminosis D

CourseCourse FormForm PeriodPeriod

Acute (as Acute (as neurotoxicosis neurotoxicosis or toxicosis or toxicosis with with dehydration of dehydration of 1-3 degree) 1-3 degree)

Chronic Chronic

NervousNervousGastro-Gastro-

intestinalintestinalRenalRenalCardio-Cardio-

vascularvascular

Clinical Clinical manifestationsmanifestations

Residual Residual signssigns

Symptoms of vitamin D Symptoms of vitamin D poisoning include:poisoning include:

Dehydration (polyuria, vomiting)Dehydration (polyuria, vomiting) Decreased appetite (anorexia)Decreased appetite (anorexia) IrritabilityIrritability ConstipationConstipation FatigueFatigue Muscle weaknessMuscle weakness

An excess of vitamin D causes An excess of vitamin D causes abnormally high blood abnormally high blood concentrations of calcium concentrations of calcium (hypercalcemia), which can cause (hypercalcemia), which can cause overcalcification of the bones, soft overcalcification of the bones, soft tissues, heart and kidneys. tissues, heart and kidneys.

Laboratory findings:Laboratory findings: A serum 25(OH)D concentration >500 A serum 25(OH)D concentration >500

nmol/L (>200 ng/mL) nmol/L (>200 ng/mL) hypercalcemia, hypophosphatemia. hypercalcemia, hypophosphatemia.

hypomagnesemia, hypokalemia, hypomagnesemia, hypokalemia, increased levels of cholesterinincreased levels of cholesterin ; ;

metabolic acidosis.metabolic acidosis. Blood: leucocytosis; Blood: leucocytosis; Urine: increase of calcium, Sulkowitch's Urine: increase of calcium, Sulkowitch's

test is positive (++++);test is positive (++++);

TreatmentTreatment To cancel immediately vit D, and limited To cancel immediately vit D, and limited

quntety of cow milk (that is rich in calcium).quntety of cow milk (that is rich in calcium). Intensive detoxicative therapy: Intensive detoxicative therapy: i.v. injections of albumin, 5% solution of glucose i.v. injections of albumin, 5% solution of glucose

with Ringer’s solution, cocarboxylase, vit C, with Ringer’s solution, cocarboxylase, vit C, prednisolone (1-2mg/kg), vit A (5-10000 prednisolone (1-2mg/kg), vit A (5-10000 IU/day), vit E, furosemid (1 mg/kg 3 times/d), IU/day), vit E, furosemid (1 mg/kg 3 times/d), thyreocalcitonin (75-150 U i.m. every day), 3% thyreocalcitonin (75-150 U i.m. every day), 3% solution of ammonium chloride (1 teaspoonful 3 solution of ammonium chloride (1 teaspoonful 3 times a day), almagel, chlolestiramine (0.5 g/kg times a day), almagel, chlolestiramine (0.5 g/kg 3 times/day),Trilon B 50 mg/kg 2-3 times/d 3 times/day),Trilon B 50 mg/kg 2-3 times/d orally, in severe cases –i.v. are used.orally, in severe cases –i.v. are used.