Approach to a child with Rickets

• Presented by: Salim AL-Huseini

SULTANTE OF OMAN

Definition of Rickets. .Types of rickets and how to differentiate

between them biochemicallyCauses of ricketsVitamin D metabolism.

Approach to patient with Rickets. Case study.

Outline

What is Rickets?

• Rickets is a disease of growing bones due todefective mineralization at growth plates in

growing children.• (Osteomalacia is the same condition in adults)• Adequate calcium and phosphate levelsare required for bone mineralization and vitamin

D is critical for calcium homeostasis

What are the different types of rickets?

a) Vitamin D deficiency- “classical rickets” caused by low endogenous vitamin Db) Vitamin D dependent-• type 1 is due to 1 alpha hydroxylase deficiency• type 2 is due to a mutation in the vitamin D

receptorc) Vitamin D resistant- defect in tubular reabsorption of phosphate

1- Nutritional

• Nutritional rickets results from inadequate sunlight exposure or inadequate intake of dietary vitamin D, calcium, or phosphorus.

• Mostly onset is at the end of the first or during the 2nd year.

In children, vitamin D deficiency is the most common cause of rickets

Vitamin D Sources

• Sun light exposure

• Diet ( liver and egg yolks )

Cholecalciferol (vitamin D-3) is formed in the skin from 7-dihydrotachysterol. This steroid undergoes hydroxylation in 2 steps.

Pathophysiology - Metabolism of vitamin D

• The first hydroxylation occurs at position 25 in the liver, producing calcidiol (25-hydroxycholecalciferol), which circulates in the plasma as the most abundant of the vitamin D metabolites

• is a good indicator of overall vitamin D status.

Cont.........

• The second hydroxylation step occurs in the kidney at the 1 position, where it undergoes hydroxylation to the active metabolite calcitriol (1,25-dihydroxycholecalciferol - DHC). This cholecalciferol is not a vitamin, but a hormone.

Pathway of Vitamin D Production

3-Pathogenesis of rickets

Vitamin D deficiency

Absorption of Ca, P

Serum Ca

Function of Parathyroid

Pathogenesis

PTH High secretion

P in urine Decalcification of old bone

P in blood Ca in blood normal or low slightly

Ca, P product

Rickets

There are three stages of vitamin D deficiency:

1. Hypocalcaemia due to poor intestinal absorption and reduced bone resorption.

2. Normal calcium and low phosphate state due to secondary hyperparathyroidism

3. Severe bone disease with recurrence of hypocalcaemia.

• What are the causes of vitamin D deficiency?

1- poor exposure to sunlight 2- dark skin ( black children) 3-. Improper feeding: 1) Inadequate intake of Vitamin D• Breast milk 0-10IU/100ml• Cow’s milk 0.3-4IU/100ml. 2) Improper Ca and P ratio

Etiology

3. Fast growth, increased requirement (relative deficiency)

4. Diseases ( malabsorption) Liver diseases, renal diseasesGastrointestinal diseases (Celiac disease, pancreatitis )Cystic fibrosis

Etiology

• Medications1) Antacids reduce absorption of calcium and

phosphate 2) Anticonvulsants ( phenytoin,phenobarbitone )Lead to increase VIT D catabolism and inhibit ca

absorption 3) Corticosteroids4) Loop diuretics

Etiology

2-Vitamin D dependent

• Vitamin D-dependent rickets, type I • is secondary to a defect in the gene that codes for

the production of renal 25(OH)D3-1-alpha-hydroxylase.

Different from simple rickets 1- early onset- 3-6 month 2- history of adequate intake of vitD and sun exposure3-normal 25 hydroy vit D but low 1,25 dihydroxy D3.

Vitamin D-dependent rickets, type II

1. is a rare autosomal disorder caused by mutations in the vitamin D receptor.

2. elevated levels of circulating calcitriol differentiate this type from type I.

3. Generalized alopecia occur in 50% of the cases .

3-Vitamin D resistant

1- familial hypophosphatemic rickets (X linked dominant.)

2-renal wasting of phosphorus at the proximal tubule level results in hypophosphatemia.

Cont…

• Clinical features.1-Early age of onset and severe

deformities2-short stature and sever dental

caries3-Normal ca, PTH, no aminoaciduria .

Type Biochemical feature

Nutritional rickets N/low ca N/low pAP and PTH high Low 25 VIT D Normal 1,25 VIT D

VIT D DEP TYPE 1 Low CA N/low pAP and PTH high Normal 25 VIT D LOW 1,25 VIT

Type 2 Low CA N/low pAP and PTH high Normal 25 VIT D high 1,25 VIT

Vitamin D resistance Normal CA , normal PTH , normal 25 VIT D Low phosphate

• A 24-month-old girl has failure to thrive and an unusual gait. She has bowed legs, thick wrists, and dental caries.

• Her weight (8 kg) and height (72.5 cm) are below the 3rd percentiles for her age.

• Her diet consists predominantly of breastfeeding 5 times daily.

• The patient's antenatal, delivery, and post-natal history are unremarkable. She lives with her parents.

Case scenario

Laboratory studies reveal

1-elevated total alkaline phosphatase 2-elevated parathyroid hormone level. 3-The 25-hydroxyvitamin D level is decreased. 4-Plain x-rays of the patient's knees and wrists

shows -metaphyseal cupping and flaring, epiphyseal irregularities, and widening of the physeal plates.

HOW to Approach to this Child??

1-HistoryThe infant's gestational age diet and degree of sunlight exposure should be noted. A detailed dietary history should include specifics of

vitamin D and calcium intake.

A family history of :• short stature• orthopedic abnormalities, • poor dentition, alopecia,• parental consanguinity may signify inherited rickets.

Cont. History.

signs and symptoms of hypocalcemia, such as muscle cramps, numbness, paresthesias, tetany and seizures

What is next?

1-complete physical and dental examinations should be performed. 2-The entire skeletal system must be palpated to search for tenderness and bony abnormalities. 3-Gait disturbances and neurologi abnormalities (such as hyperreflexia) in all children should be sought

2-Physical examination

1-head • 1-Craniotabes manifests

early in infants• 2-frontal bossing and

delays the closure of the anterior fontanelle.

• 3-Increased incidence of cavities in the teeth (dental caries)

Frontal bossing

Craniotabes

Clinical signs

1-rachitic rosary

2-Pigeon chest

3- The weakened ribs pulled by muscles also produce flaring over the diaphragm, which is known as Harrison groove.

Rib beading (rachitic rosary)

2-Thorax

Chest deformity

Funnel chest – pectus excavatum

Pigeon chest

• 1-Bowlegs and knock-knee

• 2-enlarged wrist and ankle(double malleoli)

• Lax ligament-hypotonia

3-extremities

Knock knee deformity (genu valgum)

Bowleg deformity (genu varum)

•(spine curves abnormally, including scoliosis or kyphosis). • In more severe instances in children older than 2 years, vertebral softening leads to kyphoscoliosis

4-Spine deformities

• 1-Generalized muscular hypotonia is observed in the most patients with clinical signs of rickets.

• Delayed walking• pot belly

5-muscles

3-Investigations

1-Biochemical investigations1-serum levels of calcium (total and ionized

with serum albumin), 2-phosphorus, 3-alkaline phosphatase (ALP) 4-parathyroid hormone5-calcidiol6-urine studies include urinalysis and levels of

urinary calcium and phosphorus.

Decreases

in serum calcium, serum phosphorus, calcidiol, calcitriol, urinary calcium.

The most common laboratory findings in nutritional rickets are:

Parathyroid hormone, alkaline phosphatase,

urinary phosphorus levels are elevated.

2- Radiological investigation

widening of the distal epyphysisfraying and widening of the metaphysis angular deformities of the arm and leg

bones.

Classic radiographic findings include

Show cupping and fraying of the metaphyseal region

• Classic radiographic findings include:

Radiographs of the knee of a 3-year-old girl with hypophosphatemia depict severe fraying of the metaphysis.

4-Treatment1. Special therapy: Vitamin D therapy

• A. General method: Vitamin D 2000-4000 IU/day for 2-4 weeks, then change to preventive dosage – 400 IU.

• B. A single large dose: For severe case, or Rickets with complication, or those who can’t bear oral therapy.

Vitamin D3 200000 – 300000 IU, im, preventive dosage will be used after 2-3 months.

Cont…

2-. 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.

3-. Plastic therapy: In children with bone deformities after 4 years

old plastic surgery may be useful.

References

1-Sri Lanka Journal of Child Health, 2013; 42(1): 40-44

2-Nelsons Essentials of pediatrics 6th ed3- Tom Lissauer Graham clayden illustrated

textbook of pediatrics 3 th ed.