Rickets presentation

Rickets

DR.KUMAR SUPRASHANT

HINDU RAO HOSPITAL AND NDMC MEDICAL COLLEGE

CALCIUM METABOLISM

Increase in calcium starts in 3rd trimester reaches a nadir in adulthood and then

declines at the rate of 1-2 % per year

Total body calcium- 1-2 kg , of which 99% lies in skeleton

Intracellular content – less (100 nmol /lt)

Extracellular content – 1000 times more (2.2- 2.6 mmol/lt ---- 8. 5 -10.5 mg/dl)

leading to a steep extracellular to intracellular gradient

50 % ionized 50% unionized

( active form and major regulator) (bound to albumin, Igs,

sulphate,phosphate ,

citrate)

Ionized calcium maintain calcium homeostasis by regulating PTH secretion

and 1,25 D production

In gut – absorbed in distal duodenum & proximal jejunum- paracellular

pathway( non saturable ) trans cellular pathway(vit D dependent).

Absorption favored by acidic PH,absence of chelators , presence of bile

which reduces formation of calcium fatty soaps and increase availability of

fat soluble Vit D.

EXCRETION- mainly by kidney- reabsorbed 65% in PCT concomitant with

Nacl absorption(passive) ; 20% in thick asc loh (passive) dependent on

level of ionized calcium through a protein paracellin 1; 10% in DCT

(actively) PTH, vit D dependent by using ca2+ATPase,ca2+ na+ exchanger.

Absorption decreased by high conc. Of Na+ in urine , increased by PTH and

Vit D.

Normally over 95 % of filtered calcium is reabsorbed

Fecal excretion is dependent on dietary intake and comes into significance in

renal diseases

PHOSPHOROUS METABOLISM

Total body content- 600 mg ( 85% in bones)

Intracellular & extracellular contents are almost equal( 1-2 mmol/l, 2.5 -4.5

mg/dl)reabsorbed in

65% of phosphate can be reabsorbed in absence of vitamin D, in its

presence increases to 90%

90% of phosphate is reabsorbed in proximal tubules( Na+Phosphate

cotransporter)

Phosphate reabsorption has a Tm(2 -6 mg per minute)

Reabsorption control- vit D increases, PTH & FGF 23 decreases

For diagnosis best to use Basal fasting levels

VIT D METABOLISM

Major dietary source – D2 (calciferol)- produced from ergosterol

Formed in body – D3( cholecalciferol) produced from 7-

dehydrocholesterol

U.V radiation of 230-313 nm required for conversion of ergo & dehydroch.

to D2 & D3

D2 absorbed in upper 2/3 rd part of intestine – goes to lymphatics (aided by

bile salt) & D3 endogenous synthesized form, both binds to globulin and

reaches liver- hydroxylation occours form 25 OH Vit D ( 25 OH

ergocalciferol & 25 OH cholecalciferol/calcifediol)

25 OH Vit D is major circulating form- 0.03% free, rest bound to vit D

binding protein(mainly) and albumin.

25 OH Vit D goes to kidney for second hydroxylation by 1α hydroxylase in

PCT to 1,25 OH Vit D( calcitriol)

Other places of 1 α hydroxylase – keratinocytes, trophoblast of placenta,

macrophages of granuloma and lymphoma.

1 α hydroxylase – induced by PTH , hyphophosphatemia

repressed by ↑ ca2+; 1,25 D; FGF 23

Action- acts through nuclear receptor- ↑ ca2+ reabsorption in gut, resorption

of bone( receptors present on osteoblast which activate RANK ligand

expression which promotes osteoclast activity), reabsorption of calcium in

renal tubels , antiproliferative effect on parathyroid.

For diagnosis 25 OH D is most appropriate ( bcoz its pool is large enough

to form sufficient 1,25 D even in deficient state so measuring 1,25 D can be

fallacious).

Sufficient levels - > 50 nmol/lt(>20 ng/ ml)

<37 nmol/lt(15 ng/ml) deficient

Adequate supplies of vitamin

D3 can be synthesized with

sufficient exposure to solar

ultraviolet B radiation

Melanin, clothing or

sunscreens that absorb UVB

will reduce cutaneous

production of vitamin D3

PARATHORMONE

↑ ca2+ flow from bone to blood

↓ Renal clearance of calcium

↑ intestinal absorption of calcium by activating vit D

In kidney-In Proximal tubule- inhibit phosphate reabsorption, activate renal

1 α hydroxylase

In Distal tubules- ↑ calcium absorption

also inhibit bicarbonate reabsorption

Bones- acute- causes resorption

chronic- causes increase in both osteoblastic and osteoclastic activity

continuous- ↑ osteoclastic activity

intermittent- ↑ bone formation

Receptors are present on osteoblast which release cytokines to activate

osteoclast.

RICKETS & OSTEOMALACIA

These are different expression of the same disease.

Lack of available calcium and phosphorus ( or both)

for mineralization of newly formed osteoid .

Called as English disease

Rickets-

Occur in children

Before fusion of epiphysis

Leads to softening of bone & deformity

Osteomalacia- occur in adult

- softening of bone

GROUPS AT RISK

• Infants

• Elderly

• Dark skinned

• Covered women

• Kidney failure patients

• Patients with chronic liver disease

• Fat malabsorption disorders

• Genetic types of rickets

• Patients on anticonvulsant drugs

PATHOPHYSIOLOGY

Metabolic abnormality- ↓ vitamin D- ↓ ca2+ - feedback ↑ in PTH – lead to overall increase calcium absorption , phosphate loss , increase mobilization of ca2+ and po43- from bone – overall negative balance of ca2+ & po43- for mineralization of bone.

Epiphysial plate abnormality

RESTING- cells sparse rounded randomly arranged

PROLIFERATIVE- cells regular flattened & arranged in column site of DNA synthesis & mitotic activity and growth in length of plate

MATURATION- columnar arrangement becomes large & more rounded, contain glycogen→ lowermost part k/a ZONE OF HYPERTROPHY –cells have ↑ lacunae shrunken nuclei, vascular buds grows from metaphysis at the base of column towards lacunae whereas bars of cartilage which are highly calcified lies in b/w columns – this entire region k/a ZONE OF PROVISIONAL CALCIFICATION.

ZONE OF PRIMARY SPONGIOSA – lower in metaphysis calcified bars surrounded by osteoblast which produce seams of osteoid around bars.

CHANGES IN GROWTH PLATE

Resting & proliferative zones are normal

Maturation zones column of cells largely

elongated as irregular tongue of cartilage

sometimes extending to metaphysis→

increased height of cartilagenous plate as well

as width.

Hypertrophic zones column of bars cannot be

identified properly

CAUSES OF CHANGES

Normally in hypertrophic zone vascular

ingrowth occours from metaphysis towards

tunnels formed by calcified cartilage which

destroys the basilar cells of hypertrophic layer

along with intervening cartilage.

IN RICKETS- calcified tunnels not formed-

vascular in growth does not occour so basilar

layer cannot be destroyed leading to increased

proliferation without destruction.

CUPPING- normally epiphyseal plate growth push against

calcified lower zones, so opposite pressure from both sides

leads to push of epiphyseal nucleus farther from metaphysis

along the axis of bone leading to longitudinal growth.

IN RICKETS- cartilage softened--calcified zone & metaphysis

collapse and spread under applied external force & intrinsic

growth force.

BIOCHEMICAL- resting and proliferative zone are normal

with normal DNA synthesis , zone of maturation is selectively

targeted along with zone of hypertrophy – respiratory paralysis

& shift from aerobic to anaerobic & HMP shunt, ↓ high energy

phosphate molecules→ ↓ RNA, protein , glycogen,

proteoglycan, polysaccharide leading to maturation arrest.But

no change in lysosomal activity.

HISTOLOGICAL FEATURES

Thinned cortex, ↑ porosity , ↓ density

Irregular haversian system

Trabecular bone is thin & porous with diminished

total no of trabeculae.

Trabeculae shows osteoid seams (thin layer of

mineralized bone surrounded by unmineralized

osteoid synthesized in preparation of mineralization

but cannot be done due to deficiency). Osteoid seams

are cardinal features but not pathognomic, width &

total no of osteoid seams is a good index of severity of

disease.

Osteoid seams generally in relation to 1

trabeculae but in one or more bones due to

very poor mineralization contain very large

ribbion like radiolucent area of osteoid seams

k/a looser’s zone/ umbauzons/ milkman

pseudofracture (VIRTUALLY DIAGNOSTIC

of osteomalacic syndrome)

PARADOX OF RICKETS

As the rickets become more severe and patient

become systemically more sicker with greater

abberation of biochemical abnormality the

changes in growth plate become less severe or

even disappear( if child survives) bcoz rickets

is a disease of growing bones with severe

systemic illness growth is suppressed due to

decreased nutrition & hypoprotenemia&

epiphyseal manifestation of rickets fade away

as they are directly related to rapidity of

growth.

CLINICAL FEATURES

AGE OF PRESENTATION

VITAMIN D DEFICIENCY RICKETS –

6 to 18 months.

NON NUTRITIONAL RICKETS

Beyond this age group.

Stereotyped can rarely diffrentiate one form

from other, infants & young children with

florid rickets manifest by 6 months of age.

Failure to thrive

Listless, apathic , irritable, hypotonic,

underweight, anemic, ligamentous laxity,

sweating of face and forehead, hypocalcemic

features

craniotabes(soft skull)

frontal bossing

Widening of suture,

persistent fontanelae

Delayed dentition, caries, enamel hypoplasia

Caput quadratum/ hot cross bun skull( cruciate pattern in skull due to widened sutures & thickening around sutures)

Rachitic rosary

Flattening of hemithorax

Harrison groove

Pigeon chest

Respiratory infection and

atelectasis

Protuberant abdomen

Widening of wrist, knee and ankle due to physeal over growth

Deformity

Toddlers: Bowed legs

(genu varum)

Deformity

Older children: Knock-knees

(genu valgum)

Deformity

windswept knees

Rachitic cat back- thoracic khyphosis, lumbar lordosis, scoliosis, waddling gait

Rachitic saber shin, coxa vara

String of pearl deformity- enlarged ends of phalanx and metacarpals with constricted joints

Hypotonia

Pathological #- especially greenstick

Tetany, PEM

Bone pain or tenderness

Clinical evaluation

Dietary history

Maternal risk factors

GI disease

Renal disease

Diagnosis

History & physical examination finding

Biochemical study

Radiographic abnormality

Special etiology confirmed with lab. test

Biochemical findings

Calcium - n/↑/↓, rarely fall below 7.5 to 8 mg/dl

Urinary calcium-↓ usually less than 3 mg/ kg / 24 hr(

below normal level of 5 mg / kg / 24 hr in children),

in adults on dietary intake of 750 to 1000 mg / day if

urinary excretion less than 200 mg/day – significant.

Fecal calcium - ↑ depends on dietary intake

Phosphate- ↓ in all cases(b/w 1- 3.5 mg/dl) except

renal osteodystrophy - ↑ due to inadequate filteration

from kidney. Best to measure basal fasting levels as

dependent on time of day, GH levels

Urinary phosphate- ↑ due to decreased tubular

reabsorption of phosphate but may be dependent on

dietary intake as well as serum levels( if high serum

conc. Excretion may be upto 300- 1000 mg/day, if low

serum conc.clearnce may be low despite ↓

reabsorption.

Better to measure % tubular reabsorption- <

85% significant, < 60% abnormal

Po43- creatinine clearance, max tubular

reabsorption, exogenous phosphate load

handling- done to diagnose hyperPTH

Alk. Phophatase - ↑(> 15 – 50 bodansky unit)

Bone biopsy

Hb, ESR

Other specefic tests

DISORD

Ca2+ Po43- PTH 25 D 1,25D Alk.ph Urine

Vit D def N/↓ ↓ ↑ ↓ ↓/N/↑ ↑ ↓ ↑

Ca2+ def N/↓ ↓ ↑ N ↑ ↑ ↓ ↑

Po43- def N ↓ N/↓ N ↑ ↑ ↑ ↓

VDDR 1 N/↓ ↓ ↑ N ↓ ↑ ↓ ↑

VDDR 2 N/↓ ↓ ↑ N ↑↑ ↑ ↓ ↑

VDRR N ↓ N N ↓ ↑ ↓ ↑

HHRH N ↓ N/↓ N ↓ ↑ ↑ ↑

RTA N ↓↓ N N ↓ ↑ ↑/↓ ↑

CRF N/↓ ↑ ↑ N ↓ ↑ N/↓ ↓

ETIOLOGICAL CLASSN & DIAGNOSIS

Dietary deficiency

Vit D def.

Decreaserd vit D - ↓ calcium -secondary hyperPTH- causes

phosphaturia & ↑ 1α hydroxylase: 1,25 D can be↑/N

(compensatory increase bcoz still 25 D pool is enough to

produce 1,25 D or ↓(in severe def of 25 D)

Metabolic acidosis – PTH induced HCO3- loss

N/↓ ↓ ↑ ↓ ↓/N/↑ ↑ ↓ ↑

CALCIUM DEFICIENCY

Calcium chelators- phytate, oxalate , fatty acid( forms

insoluble soap with calcium) excessive phosphate

(forms insoluble salt with calcium)

N/↓ ↓ ↑ N ↑ ↑ ↓ ↑

Phosphate def.

Rare (bcoz almost all food are sufficient enough in phosphate)

N ↓ N/↓ N ↑ ↑ ↑ ↓

Absorptive defect- can be gastric( post surgery) biliary( bile salts are required for proper emulsification of fat soluble vit D) enteric ( malabsorption syndromes)

VDDR TYPE 1

Defect in 1 α hydroxylase

1,25 D is decreased in spite of hypophosphatemia & ↑

N/↓ ↓ ↑ N ↓ ↑ ↓ ↑

VDDR TYPE 2

Defect in Vit D receptors

1,25 D ↑↑

N/↓ ↓ ↑ N ↑↑ ↑ ↓ ↑

RENAL TUBULAR RICKETS

Spectrum of renal tubular abnormalities causing hypophosphatemic rickets having resistance to vit D to varied extent

Pathophysiology –

↑ phosphate clearance due to ↓ reabsorption

Failure to produce H+ ions & and its substitution with fixed base in distal tubules

Failure of conversion of 25 OH D to 1, 25 OH D

Two theories has been given for pathogenesis –

1)Renal tubular deficit is primarily genetic due to which vitD cannot cause phosphate reabsorption whereas ca2+

absorption is normal in gut.

2) Either defect in hydroxylation of vitamin D or end

organ insensitivity to vitamin D( primary lesion is

calcium deficiency leads to increase in PTH which

causes phosphate wastage)

PHOSPHATONIN

A humoral mediator that decreases –

Renal tubular reabsorption of phosphate

Decreases hydroxylation of vitamin D

Decreased reabsorption of po43- due to phosphatonin

cause hypophosphatemia which should ↑ 1α

hydroxylase activity(1α hydroxylase activity

increased by PTH & ↓ po43- ) but phosphatonin ↓ the

activity of 1α hydroxylase also so in these conditions

rather than increase, a decrease occours in the the

level of 1,25,OH D.

FGF-23– well known phosphatonin

Renal tubular rickets can be broadly divided into 3

catogeries

A. Proximal tubular lesions

B. Distal tubular lesions

C. Proximal and distal tubular lesions

General biochemical picture

With some specific findings acc. to disease

VDRR N ↓ N N ↓ ↑ ↓ ↑

PROXIMAL TUBULAR LESIONS

4 TYPES

1)Classical Vit D resistant rickets( hypophosphatemicrickets/ phosphate diuresis)- Commonest form

X linked HPOPHOSPHATEMIC RICKETS- primary

mode of inheritance X linked dominant. Defective

PHEX(phosphate regulating gene with homologies to endopeptidase on x

chromosome) gene which is required to inactivate FGF23.

In presence of defective PHEX there is ↑ FGF 23

leading to abnormality.

ADHR- mutation in FGF23 which prevents degradation

of FGF23 by proteases.

ARHR- mutation in dentin matrix protein 1 which

results increase in FGF-23.

May be recognized at about 3 months milder forms at

about 2-3 years, sometimes hypophosphatemia may

be only finding. Unlike deficiency rickets hypotonia

& other systemic findings are less & overt

manifestations are mainly confined to skeletal systems

X ray- features of rickets, metaphyseal lines shows sclerotic

lines at irregular intervals, In adults looser zones are less

common.

% tubular reabsorption of phosphate is 40- 70%.

Most striking feature is failure to respond toVit D even

massive doses

2)VDRR WITH GLYCOSURIA- hypophosphatemic

rickets with glycosuria without diabetes or pancreatic

disease.

3) PROXIMAL FANCONI SYNDROME- phosphate,

glucose & AA wastage. Serum AA is normal. The

disease is more florid than above two but less

refractory to treatment with Vit D.

4) Rare type which manifest in adulthood & PTH action

on tubules is cause of defect rather than primary

tubular defect.

PROXIMAL AND DISTAL TUBULAR LESIONS

features common to syndromes in this group

Aminoaciduria with normal serum AA,Dehydration,

alkaline urine(bicarbonate loss)

acidosis,hyperchloremia, hyponatremia,

hypokalemia

1)Proximal and distal fanconi syndrome-

Due to anatomical defect in renal tubules

Autosomal recessive, less refractory to treatment

May be secondary to multiple myeloma or toxic drug

reaction

Epiphyseal plate several centimeter in height.

2) lignac fanconi syndrome(cystinosis)

Metabolic abnormality as above with cystine deposition throughout soft tissue( doubly refractile crystal on slit lamp examination). Disease difficult to treat & patient rarely survives beyond ten years of age despite adequate treatment.

3) Occulocerebral syndrome/ lowe’s syndrome

Features of rickets, undescended testes, CNS abnormality- MR, hypotonia ,dyskinetic movements, nystagmus, megalocornea, glaucoma, mixture of glomerular(rbc, wbc cast) PT & DT lesion- gives above metabolic abnormality.less refractory to treatment.

4)superglycine syndrome- hypophosphatemic rickets

withhyperglycinuria

RENAL TUBULAR ACIDOSIS

Two types-

Type 1- distal tubular lesion

Type 2- proximal tubular lesion

Hyponatremic hypokalemic hyperchloremic normal anion gap metabolic acidosis with alkaline urine in type 1 and acidic urine in type 2 with dehydration

Cause of bone lesion – excretion of calcium as fixed base

RTA N ↓↓ N N ↓ ↑ ↑/↓ ↑

Causes chronic hypocalcemia and secondary hyperPTH

which cause bicarbonate loss and mobilization of

calcium from bone due to acidosis. Intestinal

absorption of calcium is decreased due to decreased

formation of 1,25 D.

Nephrocalcinosis due to chronic hypercalciuria and

decreased citrate excretion in urine

All combined proximal and distal tubular lesion is

somewhat associated with RTA.

HEREDITARY HYPOPHOSPHATEMIC RICKETS

WITH HYPERCALCIURIA

Mutation of Na+ po43- cotransporter in proximal tubules phosphate leaks out- hypophosphatemia- ↑ 1,25 Vit D

- ↑ calcium absorption- ↓ PTH – causes hypercalciuria

HHRH N ↓ N/↓ N ↓ ↑ ↑ ↑

RENAL OSTEODRYSTROPHY

Chronic glomerular disease resulting in renal

insufficiency, azotemia & acidosis has profound effect

on skeletal system which include rickets, osteomalacia

osteitis fibrosa cystica, osteoporosis, osteosclerosis &

metastatic calcification.

Reduction in renal mass leads to poor conversion of 25

D to 1,25 D→ poor absorption of calcium from gut.

CRF N/↓ ↑ ↑ N ↓ ↑ N/↓ ↓

Renal excretion of calcium N/↓ probably reflecting the

↓ glomerular flow and contraction of extracellular

pool( <60 mg/24 hr)

Fecal excretion of calcium ↑ due to decreased transport

across gut wall.

Serum calcium levels are often N/ ↓ but marked

hypocalcemia is unusual, since uremic patient is

acidotic & hypoalbumenic – both contribute to

increase in % of total calcium in the ionized form so

hypocalcemic tetany is a rare finding although total

calcium is less.

Po43- levels are raised caused by decreased glomerularfiltration.

PTH levels are raised due to feedback stimulus from hypocalcemia & hyperphosphatemia

Urinary phosphate loss is increased presumably bcoz of ↑ PTH levels.

Metabolic changes results in classical osteitis fibrosa cysticaby favoring the formation of labile calcium carbonate at the expense of more stable calcium apatite.

Osteosclerosis- Theories

Exaggerated response of bone during healing phase with excessive amount of osteoid being laid down & mineralized

In uremic osteodystrophy a factor elaborated by PTH acts to increase bone formation rather than decreasing it.

Can be bcoz of sporadic period of excessive treatment with ca2+ , Vit D or both

Soft tissue calcification

metastatic calcification usually results from ↑ conc. of

ca2+ & po43- more than solubility product of CaHPo4

favored by acidosis, prolonged bed rest.

Unless the child is severe ill classical features of rickets are

present, craniotabes & frontal bossing are less common

Bowing is common

Prone to epiphyseal separation & metaphyseal #

Palpable arteries due to calcification

X ray-

Osteitis fibrosa cystica

Diffuse rarefaction of bone

Subperiosteal resorption of cortices particularly in small bones of hand & feet

Brown tumors- are cystic areas in shaft of long & flat bones

Compression # of vertebra

Osteosclerosis of spine – Rugger jersey spine

Vascular & soft tissue calcification visible on x-ray

OTHER CAUSES

Tumor-induced rickets

McCune-Albright syndrome

Epidermal nevus syndrome

Neurofibromatosis

Associated with anticonvulsant therapy

DUE TO OVER

PRODUCTION OF

PHOSPHATONIN-

RADIOGRAPHIC FINDINGS

X-RAY – LOOSER ZONE

lateral indentation of the

acetabulam (trefoil pelvis)

RUGGER JERSEY SPINE

SECONDARY HYPERPARATHYROIDISM

Cortical erosion

Pathological #

Brown tumor

Practical approach to child with rickets.

Level 1. Is it true rickets or rickets like states ?

Do preliminary investigations –

Serum calcium, phosphate, SAP

Have a close look at the x rays

Consider the following conditions –

Hypophosphatasia,

Metaphyseal dysplasia

Features

Radiological signs similar to rickets. But growth plate are not wide with differential involvement of bones in a joint.

Eg. Femur shows changes but tibia is normal.

Levels of serum Ca, P and SAP normal.

Diagnosis

Metaphysial dysplasia

Features

Clinical signs or rickets are present but x rays show tongue like radiolucency projecting from growth plate into metaphysis whereas in rickets growth plate is uniformly wide.

Very low level of Alk.ph.

Normal level of ca2+ & po43-

↑ serum conc. & excretion of phosphoethanolamine

Diagnosis -- Hereditary Hypophasphatasia ( 0ccours due to genetic error in synthesis of alkaline phosphatase)

level 2 – is it nutritional or non nutritional ?

Look for clues in the history or examination-

prematurity

neonatal cholestasis

anticonvulsant therapy

chronic renal disease

Jaundice - hepatobiliary disease

metabolic disorders

Cataract - galactosemia, wilsons

Positive family history - metabolic disease,

Mental retardation, seizures - Galactosemia,

drug induced rickets in primary CNS problem

Alopecia - VDDR type 2.

In the absence of clues –

Presume and treat it as vit D deficiency rickets. Give vitamin D3 (calcitriol) 600000 units 2 doses at four weeks interval . Improvement occurs in nutritional rickets.

Healing is indicated by the presence of provisional zone of calcification.

Non healing favours a non nutritional cause.

FEATURES OF NON NUTRITIONAL CAUSES

Presentation before six months or after two years of age

Associated failure to thrive

Positive family history

Obvious clues

Failure of vitamin D therapy

LEVEL 3. IF IT IS NON NUTRITIONAL AND LACK ANY

OBVIOUS CLUES IT COULD BE EITHER DUE TO GI

OR RENAL CAUSE

Features

Recurrent diarrhea, oily stools.

Recurrent abdominal pain and distension.

Anemia, hypoproteinemia.

Multiple vitamin and mineral deficiencies.

Diagonosis - Malabsorption with rickets.

Features

Hepatobiliary findings.

Raised serum bilirubin, low serum albumin and prolonged prothrombin time.

Diagnosis - Hepatic rickets

Features

Failure to thrive, rec. vomiting, lethargy, acidoticbreathing.

Hypertension, anemia with or without edema.

Positive findings in urine analysis.

Abnormalities in electrolytes, blood urea and creatinine.

Renal abnormalities in ultrasound abdomen.

Diagnosis –Renal rickets.

LEVEL 4.. IF IT IS RICKETS DUE TO RENAL

CAUSES WHAT IS THE UNDERLYING RENAL

PROBLEM THAT LED TO RICKETS.?

Depends on the clinical features of chronic renal failure and on laboratory investigations.

Do urine analysis..

blood for electrolytes, urea and creatinine.

blood gas analysis.

ultrasonography of abdomen.

Features…

Vomiting , lethargy, growth retardation

Hypertension, anemia, with or without edema.

Features of obstructive uropathy.

Raised blood urea, creatinine, S. potassium may be high.

Abnormalities in USG, MCU and DMSA scan.

Diagnosis – Chronic renal failure - renal osteodystrophy.

Features…

Recurrent vomiting, diarrhoea with acidotic breathing.

Positive family history.

Metabolic acidosis with normal anion gap, hypokalemia, and hyperchloremia

Normal blood urea and serum creatinine.

No proteinuria or glycosuria.

Diagnosis - Renal tubular acidosis.

Features

Severe form of rickets with stunting and deformity.

Features mentioned in RTA.

Proteinura, glycosuria present.

Normal or slightly increased B.urea and S.creatinine.

Features of underlying causes such as cystinosis.

Diagnosis. - Fanconi syndrome.

Features

Lower limb deformity, stunted growth.

Often with family history.

Frequent dental abscess and early decay.

Low serum phosphate and low TRP.

Reduced 1,25 D in soite of hypophosphatemia

Diagnosis – Familial hypophosphataemicrickets(FHR).

LEVEL 5.. CHILD WITH RICKETS, NO CLUES SO

FAR, WHAT ELSE?

Features

Often presenting in early infancy.

Hypocalcemic tetany.

Improvement with vitamin D therapy and recurrence of symptoms on discontinuation.

Diagnosis - vitamin D dependent rickets type 1

Features

Alopecia without any response to any form of vitamin D

High serum levels of 1,25 dihydroxy vitamin D.

Diagnosis – vitamin D dependent rickets type2

(1,25(OH)2 vit D level is high in contrast to VDDR type 1 where it is low.)

TREATMENT

There is no simple regimen for treatment for such a

varied entity and even within each category the

treatment must be carefully tailored to meet the needs

of individual patient.

Generally treatment include combination of vit D , ca2+ ,

phosphate, alkalinizing solution

Orthopaedic measures may be required to correct

deformities that cannot be expected to improve with

growth.

Standard dosing

(A) Administer 1000–2000 IU of vitamin D3 orally per day until radiographic improvement is seen, then switch to 400 IU per day

(B) Administer 8000–16,000 IU of vitamin D3 orally per day until

radiographic resolution, then switch to 400 IU per day

Stosstherapy

(C) Administer 600,000 IU of vitamin D3 orally in 6 doses

(100,000 IU/dose) every 2 hours over a 12-hr period, followed

by supplemental vitamin D3 (400 IU/day)

(D) Administer 150,000–300,000 orally as a single dose

(E) Administer 600,000 IU intramuscularly as a single dose, then

400 IU per day

Data from Levine and Carpenter,5 Shah and Finberg,6 Cesur et al,7

and Lubani et al.8

Estimated daily requirement of Vit D

Children -200 to 400 IU

Adult- 100 to 400 IU

1 mg of vit D = 40,000 IU

1 µ gm = 40 IU

Amount of calcium that can be taken orally- 1 to 1.5gm/day.

If sufficient Vit D is administered upto 0.5 gm can be

absorbed. There is probably no role of I.V calcium to treat

rachitic syndrome except in emergency such as acute

hypocalcemic tetany or cardiac failure.

Alkalinizing solution – sodium bicarbonate, shohl’s solution

EVALUATION OF TREATMENT Serial mesurement of alkaline phosphatase

Serial measurement of serum po43-

serial roentgenographic examination shows progressive healing

when alk.ph, po43- return to normal range and x ray shows progressive healing – treatment is adequate

In addition if there are no side effects and growth is adequate – treatment optimal

Osteomalacia- repeated biopsies of iliac crest to show improvement in mineralization.

serial measurement of % tubular reabsorption of po43-.

Radiological healing is evident at about 4 weeks of therapy. If no healing is evident at 4 weeks of therapy patient should be evaluated for refractory rickets.

IMP. TO DIAGNOSE POTENTIAL SIDE EFFECTS

Serial measurement of serum calcium and urinary calcium excretion

Serum ca2+ > 11 mg/dl

Urinary ca2+ excretion > 250 mg/24 hr

Can lead to nephrocalcinosis and soft tissue calcification

Whereas urinary calcium <100 mg/dl – shows inadequate

treatment.

TOXICITY

• Hypervitaminosis D

causes hypercalcemia, which manifest as:

Nausea, vomiting, ↓Appetite

Excessive thirst & polyuria

Severe itching

Joint & muscle pains

Disorientation & coma.

Soft tissue & vessel calcification

ORTHOPAEDIC MEASURES

Deficiency rickets

If t/t given earlier, deformity correct spontaneously

Long standing case and Vit-D resistant rickets

Mild deformity----------brace

(Mermaid splint for knock knee)

If deformity is mark----osteotomy

WHO SHOULD BE TESTED FOR VIT D DEFICIENCY

HOW DO WE TREAT

Rickets presentation

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Update on Hypophosphatemic Ricketspediatrics.med.miami.edu/documents/...Rickets... · Clarification All types of rickets are hypophosphatemic (after all we now know that rickets is

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