2.

Common Nutritional Disorders

• Breastfeeding
• Failure To Thrive
• Severe Childhood Undernutrition
• Rickets (including vitamin D, calcium, and phosphorous
deficiency)
• Hypervitaminosis D

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 BREASTFEEDING
Beneficial Properties of Human Milk Compared with Formula

ANTIBACTERIAL FACTORS
• Secretory IgA: specific antigen-targeted anti-infective action.
• Lactoferrin: immunomodulation, iron chelation, antimicrobial action,
antiadhesive, trophic for intestinal growth.
• Casein: antiadhesive, bacterial flora.
• Oligosaccharides: prevention of bacterial attachment.
• Cytokines: antiinflammatory, epithelial barrier function.
GROWTH FACTORS
• Epidermal growth factor: luminal surveillance, repair of intestine.
• Transforming growth factor (TGF): promotes epithelial cell growth
and suppresses lymphocyte function.
• Nerve growth factor: promotes neural growth.
ENZYMES
• Platelet-activating factor (PAF)-acetylhydrolase: blocks action of
PAF.
• Glutathione peroxidase: prevents lipid oxidation.
• Nucleotides: enhance antibody responses, bacterial flora.

Ten Steps to Successful Breastfeeding

1. Have a written breastfeeding policy that is routinely communicated to

all healthcare staff.
2. Train all healthcare staff in the skills necessary to implement this
policy.
3. Inform all pregnant women about the benefits and management of
breastfeeding.
4. Help mothers initiate breastfeeding within a half hour of birth.
5. Show mothers how to breastfeed and how to maintain lactation even
if they should be separated from their infants.
6. Give newborn infants no food or drink other than breast milk unless
medically indicated.
7. Practice rooming-in, i.e., allow mothers & infants to remain together
24 hr a day.
8. Encourage breastfeeding on demand.
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9. Give no artificial teats or pacifiers to breastfeeding infants.
10. Foster the establishment of breastfeeding support groups and
refer mothers to them on discharge from the hospital or clinic.

Signs of insufficient milk intake include:-

Lethargy, delayed stooling, ↓ urine output, weight loss >7% of birth
weight, hypernatremic dehydration, inconsolable crying, and ↑ hunger.
When there is maternal fear about insufficient breast milk production,
encourage her to ↑ intake of fluids and nutritious diet e.g. milk. Small
dose of chlorpromazine for few days can also ↑ breast milk production.

Medical Contraindications to Breastfeeding

• Maternal conditions include infections with: HIV; human T-cell

lymphotropic virus; CMV (in preterm); active TB (until appropriately
treated ≥2 wk and not considered contagious); herpes virus infection
of breast (until healing); septicemia, typhoid fever, syphilis, and
malaria (until adequately treated); and HBV (unless the infant receive
HBIG & vaccine).
Note: Mastitis is not a contraindication for breast feeding; instead
continue feeding to ↓ breast engorgement, with antibiotics & local heat
application.
Other maternal conditions include medications that are
contraindicated with breast feeding (see later), as well as breast
cancer, substance abuse, and severe neurosis or psychosis.
• Infants with galactosemia, maple syrup urine disease, and phenylke-
tonuria are contraindicated for breast feeding.

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 FAILURE TO THRIVE
FTT is usually a diagnosis of infants & children below 3 yr of age whose
growth is less than that of their peers. Although there is no one set of
growth parameters provide a criteria for universal definition, it is
classically refers to as either weight below 3rd or 5th percentile or
change in weight that crossed 2 major percentiles in a short time.

Et. It is often multifactorial, but generally can be divided into organic &
non-organic causes:-
❖ Organic FTT may include any chronic severe illness that affect any
system of the body.
❖ Non-organic (Psychosocial) FTT include:-
• Inadequate diet because of poverty, food insufficiency, or errors in
food preparation.
• Poor parenting skills (lack of knowledge of sufficient diet).
• Child/parent interaction problems (autonomy struggles, coercive
feeding, maternal depression).
• Parental cognitive or mental health problems.
• Child abuse or neglect, emotional deprivation.
• Rumination, a rare disorder associated with repeated regurgitation
and rechewing of food.

In another way, FTT can also be due to either:-

▪ Failure of provision of sufficient food.
▪ Failure to ingest and utilize sufficient food.
▪ Malabsorption.
▪ ↑ metabolic demands.

C.M. It ranges from just poor growth in comparison with their peers to a
manifestations similar to those of severe malnutrition (see below).

In psychosocial FTT, there may be signs of neglect e.g. diaper rash,

unwashed skin, untreated impetigo, uncut and dirty fingernails, or
unwashed clothing. A flattened occiput with hair loss may indicate that
the infant has being unattended for prolonged periods. Other features
may include delays in social and speech development, avoidance of eye
contact, expressionless face, & hypotonia.

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Approach to Infant with FTT
The hx in any patient with FTT must include a detailed dietary hx with
observation of maternal-child interaction. Physical examination should
include all systems of body that may affect growth.

Measure periodically all growth parameters including; weight,

length/height & (weight/height) ratio to measure the degree of FTT. In
malnutrition, weight is the 1st to be affected, followed by height,
whereas head circumference is lastly affected when malnutrition is
seriously affect brain growth.

• Classification of FTT according to severity:-

Mild Moderate Severe
✓ Weight: < 90% < 75% < 60%
✓ Height: < 95% < 90% < 85%
✓ wt/ht ratio: < 90% < 80% < 70%

Note: This classification is depend on the percentage from the median

body weight, height & wt/ht that are taken from appropriate growth
charts (according to patient's age & sex) at the 50th percentile.

Z scores or standard deviation [SD] scores is the child's height (weight)

minus the median height (weight) for the child's age and sex divided by
the relevant SD. SD >-3 indicate severe, between -3 & -2 indicate
moderate, <-1 indicate mild stunting (wasting) respectively.

Special growth charts are available for patients with genetic syndromes
e.g. Down & Turner. For premature infants, use either a special chart or
the corrected age, for example; if a premature infant is delivered at 30
wk gestational age and the current postnatal age is 10 wk, then
postconceptual age = 40 wk, this infant is considered in the same age as
a fullterm newborn delivered at 40 wk. However, most VLBW infants
will achieve weight catch-up with their peers during the 2nd yr and
height by ≈ 3rd yr of age.

Inv. CBP & GUE are good initial tests. Other tests should be judicious &
relevant to the findings in the history or examination.

Rx.
Indications of hospitalization for patients with FTT include:-
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 For further investigations, severe malnutrition, failure of home
management, & to evaluate the parent-child feeding interaction
(especially when psychosocial FTT is suspected).
• Organic causes of FTT should be treated according to the etiology of
the organic illness as well as with good nutrition.
• Inorganic (Psychosocial) FTT should initially be treated at hospital
by giving age-appropriate unlimited diet. If the infant start to gain
weight, this is mostly due to Inorganic FTT. However, children with
severe malnutrition must be re-fed carefully to avoid re-feeding
syndrome (see later).

In most cases, cow’s milk–based formulas are tolerated and provide

an appropriate mix of nutrients. Other easily digested foods,
appropriate for the age, also may be introduced slowly. If feeding
intolerance occurs, lactose-free or semi-elemental formulas should be
considered.
Goals of Rx are to obtain catch-up growth by gaining at least 30 g/day
from the 1st wk & also to educate the mother (with the help of the
nursing staff) about appropriate food & feeding style e.g. Rule of 3s (3
meals, 3 snack, and 3 choices). These children should also be given
multivitamins as they usually have deficiency of iron, zinc, & vit D.

Pg. Malnutrition causes defects in host defenses. Children with FTT may
suffer from a malnutrition-infection cycle, in which recurrent
infections exacerbate malnutrition → greater susceptibility to infection.
FTT in the 1st yr of life (regardless of cause) is ominous, because
maximal postnatal brain growth occurs in the 1st 6 mo of life as well as
brain grows as much in 1st yr as in the rest of the child's life. Thus all
patient with FTT require frequent monitoring & assessment.
Prognosis of patients with organic FTT is variable, whereas ≈ 30% of
children with psychosocial FTT may develop developmental delay with
social and emotional problems.
Early FTT may be associated with ↑ risk factors for cardiovascular
disease e.g. dyslipidemia, HT, and glucose intolerance as an adult.

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 SEVERE CHILDHOOD UNDERNUTRITION
These terms are applicable to children at all ages. Causes are usually
similar to those of FTT.
C.M.
Face Moon face (kwashiorkor), simian facies (marasmus)

Eye Dry eyes, pale conjunctiva, Bitot spots (vit A), periorbital edema

Angular stomatitis, cheilitis, glossitis, spongy bleeding gums (vit

Mouth
C), parotid enlargement

Teeth Enamel mottling, delayed eruption

Dull, sparse, brittle hair, hypopigmentation, flag sign

Hair
(alternating bands of light and normal color), alopecia

Loose and wrinkled (marasmus), shiny and edematous

(kwashiorkor), dry, follicular hyperkeratosis, patchy hyper- and
Skin
hypopigmentation (crazy paving or flaky paint dermatoses),
erosions, poor wound healing

Nails Koilonychia, thin and soft nail plates, fissures or ridges

Muscle wasting, particularly buttocks and thighs; Chvostek or

Musculature
Trousseau signs (hypocalcemia)

Deformities, usually as a result of calcium, vitD or vitC

Skeletal
deficiencies

Distended: hepatomegaly with fatty liver; ascites may be

Abdomen
present

Bradycardia, hypotension, reduced cardiac output, small vessel

Cardiovascular
vasculopathy

Global developmental delay, loss of knee and ankle reflexes,

Neurologic
impaired memory

Hematologic Pallor, petechiae, bleeding diathesis

Behavior Lethargic, apathetic, irritable on handling

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Note: Bilateral edema is diagnosed in kwashiorkor by grasping both feet,
placing a thumb on top of each, and pressing gently but firmly for 10 sec. A
pit (dent) remaining under each thumb.

Height-for-age (or length-for-age for children <2 yr) is a measure of

linear growth, and a deficit represents the cumulative impact of adverse
events, usually in the first 1000 days from conception, that result in
stunting or chronic malnutrition. A low height-for-age typically reflects
socioeconomic disadvantage.
Weight-for-age is the most commonly used index of nutritional status,
although a low value has limited clinical significance because it does not
differentiate between wasting and stunting. Weight-for-age has the
advantage of being somewhat easier to measure than indices that
require height measurements.
A low weight-for-height usually indicates acute malnutrition.
Conversely, high weight-for-height indicates overweight.
In humanitarian emergencies and some community or outpatient
settings, mid-upper arm circumference (MUAC) is used for screening
wasted children.
Body mass index (BMI) is calculated by dividing weight in kilograms
by the square of height in meters. For children, BMI is age and gender
specific. BMI for age can be used from birth to 20 yr and is a screening
tool for thinness (>-2 SD), overweight (between +1 SD and +2 SD), and
obesity (>+2 SD).

Inv. CBP, CRP, GUE, GSE, RBS, RFT, total serum protein & serum albumin
(which is low in both marasmus & kwashiorkor).

Rx. of undernutrition involve 3 phases: stabilization, rehabilitation &

follow-up.

1. Stabilization phase (1st wk)

There are several steps for stabilization of patient with severe
malnutrition include:-
Step Prevention Management
Hypoglycemia Avoid long gaps If conscious:
(blood glucose <3 without food and 1. Give 10% glucose (50 mL), or a feed
mmol/L) minimize need for (see step 7), or 1 tsp sugar under
glucose: tongue, whichever is quickest.
1. Feed immediately. 2. Feed every 2 hr for at least 1st day.

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 2. Feed every 3 hr day Initially give 1/4 of feed every 30 min.
and night (2 hr if ill). 3. Keep warm.
3. Feed on time. 4. Start broad-spectrum antibiotics.
4. Keep warm. If unconscious:
5. Treat infections 1. Immediately give sterile 10% glucose
(they compete for (5 mL/kg)
glucose). 2. Feed every 2 hr for at least 1st day.
Note: Hypoglycemia Initially give 1/4 of feed every 30 min.
and hypothermia often Use nasogastric (NG) tube if unable to
coexist and are signs of drink.
severe infection. 3. Keep warm.
4. Start broad-spectrum antibiotics.
Hypothermia Keep warm and dry Actively rewarm.
(axillary <35°C; and feed frequently. 1. Feed.
rectal <35.5°C) 1. Avoid exposure. 2. Skin-to-skin contact with caregiver
2. Dress warmly, “kangaroo technique” or dress in
(including head) and warmed clothes, cover head, wrap in
cover with blanket. warmed blanket and provide indirect
3. Keep room hot; heat (e.g., heater; transwarmer
avoid drafts. mattress; incandescent lamp).
4. Change wet clothes 3. Monitor temperature hourly (or every
and bedding. 30 min if using heater).
5. Do not bathe if very 4. Stop rewarming when rectal temp is
ill. 36.5°C
6. Feed frequently day
and night.
7. Treat infections.
Dehydration Replace stool losses. Do not give IV fluids unless the child is in
Give ReSoMal after shock.
each watery stool. 1. Give ReSoMal 5 mL/kg every 30 min
ReSoMal (37.5 mmol for 1st 2 hr orally or by NG tube. Then
Na/L) is a low- sodium give 5-10 mL/kg in alternate hours for
rehydration solution up to 10 hr. Amount depends on stool
for malnutrition. loss and eagerness to drink. Feed in the
other alternate hour.
3. Monitor hourly and stop if signs of
overload develop (pulse rate increases
by 25 beats/min and respiratory rate by
5 breaths/min; increasing edema;
engorged jugular veins).
4. Stop when rehydrated (≥3 signs of
hydration: less thirsty, passing urine,
skin pinch less slow, eyes less sunken,
moist mouth, tears, less lethargic,
improved pulse and respiratory rate).
Electrolyte Give extra potassium (4 mmol/kg/day)
Imbalance and magnesium (0.6 mmol/kg/day) for
(deficit of K & Mg, at least 2 wk.
excess Na) Note: K and Mg are already added in
Nutriset F75 & F100 packets.
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Infections Minimize risk of cross- Infections are often silent. Starting on
infection. 1st day, give broad-spectrum antibiotics
1. Avoid overcrowding. to all children.
2. Wash hands. If no complications, give Amoxicillin, 25
3. Give measles vaccine mg/kg PO twice daily for 5 days. If
to unimmunized complications (shock, hypoglycemia,
children age >6 mo. hypothermia, skin lesions, respiratory or
urinary tract infections, or
lethargy/sickly), give Gentamicin, 7.5
mg/kg IV or IM once daily for 7 days and
Ampicillin, 50 mg/kg IV or IM every 6 hr
for 2 days, then amoxicillin, 25-40
mg/kg PO every 8 hr for 5 days.
For persistent diarrhea or small bowel
overgrowth, add metronidazole, 7.5
mg/kg PO every 8 hr for 7 days.
Note: Avoid steroids because they
depress immune function.
Micronutrient multivitamins, folic Do not give iron in the stabilization
deficiencies acid, zinc, copper, and phase.
other trace minerals 1. Give vitamin A on day 1 (<6 mo
are already added in 50,000 units; 6-12 mo 100,000 units;
Nutriset F75 and F100 >12 mo 200,000 units) if child has any
packets. eye signs of vitamin A deficiency or has
had recent measles. Repeat this dose on
days 2 and 14.
2. Give folic acid, 1 mg (5 mg on day 1).
3. Give zinc (2 mg/kg/day) and copper
(0.3 mg/kg/day). These are in the
electrolyte/mineral solution and
Combined Mineral Vitamin mix (CMV)
and can be added to feeds and ReSoMal.
4. Give multivitamin syrup or CMV.
Start cautious 1. Give 8-12 small feeds of F75 to
feeding provide 130 mL/kg/day
2. If gross edema, reduce volume to 100
mL/kg/day.
3. Keep a 24-hr intake chart. Measure
feeds carefully. Record leftovers.
4. If child has poor appetite, coax and
encourage to finish the feed. If
unfinished, reoffer later. Use NG tube if
eating ≤80% of the amount offered.
5. If breastfed, encourage continued
breastfeeding but also give F75.
6. Transfer to F100 when appetite
returns (usually within 1 wk) and
edema has been lost or is reduced.
7. Weigh daily and plot weight.

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 If the patient with severe malnutrition is in shock, then give oxygen, IV
glucose 10% (5 mL/kg). IV fluid shoot at 15 mL/kg over 1 hr, using:
Ringer lactate with 5% dextrose or Half-normal saline with 5% dextrose
Half-strength Darrow solution with 5% dextrose. If all the above are
unavailable, use Ringer lactate. Measure and record pulse and
respirations at the start and every 10 min.
If there are signs of improvement (pulse and respiration rates fall)
repeat IV drip, 15 mL/kg for 1 more hr. Then switch to oral or
nasogastric rehydration with ReSoMal, 5-10 mL/kg in alternate hr.

If there are no signs of improvement, assume septic shock and:

1. Give maintenance fluid IV (4 mL/kg/hr) while waiting for blood.
2. Order 10 mL/kg fresh whole blood and transfuse slowly over 3 hr.
If signs of HF, give 5-7 mL/kg of packed cells rather than whole blood.
3. Give furosemide, 1 mL/kg IV at start of transfusion.
Note: The above amount of blood also can be given for patient with very
severe anemia i.e. Hb 4-6 g/dL with respiratory distress.

2. Rehabilitation phase (2nd wk-6th wk)

It involves feeding with F100 formula (100 kcal/100 ml). To make the
transition, for 2 days replace F75 with an equal volume of F100, then
increase each successive feed by 10 mL until some feed remains
uneaten (usually at about 200 mL/kg/day) and continue to give
potassium, magnesium, and micronutrients e.g. iron (3 mg/kg/day). If
oral feeding is not tolerated, give it by NG tube.
Another approach is the use of Ready to Use Therapeutic Foods
(RUTFs); a mixture of powdered milk, peanuts, sugar, vitamins, and
minerals. It reduce mortality in a cost-effective manner because they are
oil-based paste that has little water content which make it less
susceptible to bacterial contamination than F100; it also has similar
nutrient profile with a higher calorie density and equally palatable to
F100.

3. Follow-up phase (7th wk till recovery)

Contiue feeding to cover catch-up growth and also provision of
emotional stimulation with the aid of family & community.

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 Refeeding Syndrome
It may occur if high-energy feeding is started too soon or too vigorous.
It may → sudden death with signs of HF. It is usually complicates the
acute nutritional rehabilitation after aggressive enteral or parenteral
alimentation. It is mainly due to severe hypophosphatemia after the
cellular uptake of phosphate.
Other features include: hypokalemia, hypomagnesemia, sodium
retention, hyperglycemia, & vitamins deficiency (especially thiamin).

C.M. Early warning signs are sudden ↑ in pulse and respiratory rates
during the transition to high-energy feeding; in addition to the features
of electrolyte disturbances.

Inv. Monitor serum Pi, K, Mg, & Ca frequently in the 1st 2 wk after Rx.

Rx. Slowly ↑ feeding; no or minimal edema and return of appetite

are signs of readiness for the transition from low- to high-energy diet.
Supplementation of minerals, vitamins (especially thiamin) &
correction of electrolytes disturbances, especially hypophosphatemia,
hypokalemia, & hypomagnessemia are important.
Note: Milk-based diets are desirable because milk is a good source of
phosphate.
Should refeeding syndrome occur, prompt Rx with a single parenteral
dose of digoxin and furosemide has been useful.

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 RICKETS
Rickets is a disease of growing bone that is due to unmineralized
protein matrix (osteoid) at the growth plates, thus it occurs only in
children before fusion of the epiphyses, whereas osteomalacia is
present when there is inadequate mineralization of osteoid throughout
bone and occurs in children and adults. Rickets remains a persistent
problem in the developing as well as developed countries.
Et.
• Vit D disorders: Nutritional, Congenital, Secondary, Vit D–dependent
rickets (type 1 & type 2), and Chronic RF.
• Calcium deficiency: Low intake or Malabsorption.
• Phosphorus deficiency: Inadequate intake, Disorders of FGF–23 e.g.
XL, AD & AR hypophosphatemic rickets, Hereditary hypophosphatemic
rickets with hypercalciuria, Overproduction of FGF–23.
• Syndromes & diseases associated with rickets: Fanconi synd, Distal
RTA & Dent disease.
C.M.
• General: FTT, listlessness, protruding abdomen, muscle weakness
(especially proximal), delayed walking, waddling gait, fractures.
• Head: craniotabes, frontal bossing, delayed fontanel closure, delayed
dentition with dental caries, craniosynostosis.
• Chest: rachitic rosary, Harrison groove, RTI and atelectasis.
• Back: scoliosis, kyphosis, lordosis.
• Extremities: enlargement of wrists and ankles, valgus or varus
deformities, windswept deformity, anterior bowing of the tibia and
femur, coxa vara, leg pain.
• Hypocalcemic symptoms: tetany, seizures, strider (due to laryngeal
spasm).
Note: Craniotabes may also be secondary to osteogenesis imperfecta,
hydrocephalus, and syphilis; it is also a normal finding in many newborns,
especially near the suture lines which is typically disappears within a few
months after birth.
Inv.
• X-ray of the wrist in AP view shows thickening of the growth plate
with fraying & cupping of distal ends of the metaphyses.

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 Other findings include coarse trabeculation of the diaphysis and
generalized rarefaction.

• Laboratory tests can be illustrated in the following table:-

Disorder PTH 25- 1,25- serum urine serum urin

(OH)D (OH)2D Ca Ca Pi Pi
Vit D deficiency ↑ ↓ ↓, N, ↑ N, ↓ ↓ ↓ ↑

VDDR, type 1 ↑ N ↓ N, ↓ ↓ ↓ ↑

VDDR, type 2 ↑ N ↑↑ N, ↓ ↓ ↓ ↑

Chronic renal ↑ N ↓ N, ↓ N, ↓ ↑ ↓
failure
Dietary Ca ↑ N ↑ N, ↓ ↓ ↓ ↑
deficiency
Dietary Pi N, ↓ N ↑ N ↑ ↓ ↓
deficiency
XL, AD & ARHR N N RD N ↓ ↓ ↑
HHRH N, ↓ N ↑ N ↑ ↓ ↑
Fanconi synd N N RD or ↑ N ↓ or ↑ ↓ ↑
Tumor-induced N N RD N ↓ ↓ ↑

RD: Relatively Decreased.

Alkaline phosphatase level is always increase in all types of rickets;

whereas parathyroid hormone (PTH) level always increase in
hypocalcemia, unless there is hypophosphatemia.

Rx. It is usually involves (in general) one or more of the following: vit D,
Ca, Pi +/_ Rx of the underlying disorder.

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 Vitamin D Disorders
Vitamin D Physiology
Cutaneous synthesis is the most important source of vit D in skin
epithelial cells from the conversion of 7-dehydrochlesterol to 3-
cholecalciferol (D3) by ultraviolet B radiation from the sun, but this
depend on the amount of sun exposure because less duration, covering
the skin with clothing, skin pigmentation, and seasonality (winter sun)
are less efficient in vit D synthesis.
Natural dietary sources of vit D (D2) include: fish liver oil, egg yolk,
plants or yeast. Vit D is fat-soluble, stable to heat, acid, alkali, and
oxidation. Bile is necessary for its absorption.
Vit D is transported bound to vit D–binding protein to the liver, where
25-hydroxlase converts vit D into 25-hydroxyvit D (25-D), which is the
most abundant circulating form of vit D & it is the standard method for
determining patient's vit D status. The final step in activation occurs in
the kidney, where 1α-hydroxylase adds a second hydroxyl group,
resulting in 1,25-dihydroxyvit D (1,25-D). This enzyme is upregulated
by PTH and hypophosphatemia.
1,25-D acts in the intestine causing marked increase in calcium
absorption and to less extent phosphorus absorption. It also has a direct
effects on bone by mediating resorption (i.e. demeniralization). 1,25-D
directly suppresses PTH secretion by the parathyroid gland (which also
suppressed by the increase in serum calcium); as well as 1,25-D inhibits
its own synthesis in the kidney. Types of vit D deficiency include:-

❖ Nutritional vitamin D deficiency

Et. It is the most common cause of rickets globally. It most commonly

occurs in infancy due to a combination of poor intake and inadequate
cutaneous synthesis. Transplacental transport of vit D (mostly 25-D)
typically provides enough vit D for the 1st 2 mo of life, unless there is
severe maternal vit D deficiency.
Infants who receive formula receive adequate vit D, even without
cutaneous synthesis. Because of the low vit D content of breast milk
(especially if the mother was also vit D deficient), thus breast-fed infants
rely on cutaneous synthesis or vit D supplements.

- 87 -
C.M. & Inv. (see above).

Elevated PTH cause increase in serum Ca by 3 ways; (1) ↑ its

absorption from intestine, which mediated by 1,25-D, (2) enhance bone
resorption, & (3) reabsorption of Ca from renal tubules, at the same
time, it ↑ renal losses and ↓ intestinal absorption of phosphate.
The wide variation in 1,25-D levels (↓, N, ↑) is secondary to the
upregulation of renal 1α-hydroxylase by concomitant
hypophosphatemia and hyperparathyroidism.
Some patients have a metabolic acidosis (due to PTH-induced renal
bicarbonate wasting); aminoaciduria also may occur.

Rx. Vit D can be given either as 300,000-600,000 IU orally or IM as 2-4

doses over 1 day "stoss therapy", or by daily vit D with a minimum dose
of 2,000 IU for a minimum of 3 mo; it should be followed by
maintenance dose of daily vit D, 400 IU/day if <1 yr, 600 IU/day if >1 yr.
It is important to ensure that children should also receive adequate
dietary calcium and phosphorus by milk, formula, and other dairy
products.
Some children with symptomatic hypocalcemia can be given either IV
calcium acutely, followed by oral calcium supplements, which can be
tapered over 2-6 wk, or may be given IV or oral 1,25-D (calcitriol).

Pg. Laboratory tests should normalize rapidly, whereas radiologic

changes may heal within few months. Many of the bone malformations
improve dramatically, but children with severe disease may have
permanent deformities (which rarely may require surgery) and short
stature.

Pv. Most cases of nutritional rickets can be prevented by universal

administration of a daily vit D 400 IU for infants < 1 yr, and
600 IU/day for older children either as supplement or multivitamin.

❖ Congenital vitamin D deficiency (congenital rickets)

Rickets manifestations at birth can occurs when there is severe

maternal vit D deficiency during pregnancy. These newborns also
may have symptomatic hypocalcemia and IUGR.

- 88 -
Rx. Vit D supplementation and adequate intake of Ca & Pi; also the use
of prenatal vit D (to the mother) can prevents this entity.

❖ Secondary vitamin D deficiency

Along with inadequate intake, vit D deficiency can develop due to

inadequate absorption or malabsorption due to a variety of liver and
intestinal diseases. This can be treated by either high doses of vit D,
especially 25-D & 1,25-D which are better absorbed than "plain" vit D,
otherwise use parenteral vit D.

Secondary vit D deficiency also may occur by increased degradation

of vit D by cytochrome P450 (CYP) system induced by some
anticonvulsants (e.g., phenobarbital, phenytoin) or antituberculosis
medications (e.g., isoniazid, rifampin). It can be treated in the same way
as for nutritional deficiency (see earlier). In both conditions, dose can be
titrated according to serum level of 25-D.

❖ Vitamin D–Dependent Rickets, Type 1

Type 1A is an AR disorder due to mutations in the gene encoding renal

1α-hydroxylase, preventing conversion of 25-D into 1,25-D. These
patients have normal level of 25-D but low level of 1,25-D. They usually
present during the 1st 2 yr of life and can have any of the classic
features of rickets.
Rx. Long-term treatment with 1,25-D (calcitriol). Initial doses are 0.25-
2 µg/day with adequate intake of calcium, then lower doses are used
once the rickets has healed to avoid hypervitaminosis D.

Type 1B is secondary to a mutation in gene for liver 25-hydroxylase.

Patients have low levels of 25-D but normal levels of 1,25-D!.
Rx. Vitamin D2 (3,000 U/day) as a result of alternative enzymes with
25-hydroxylase activity or residual activity of the mutant protein.

❖ Vitamin D–Dependent Rickets, Type 2

Type2A is an AR disorder due to mutations in the gene encoding vit D

receptor. These patients have extremely high level of 1,25-D and
usually present during infancy, but less severely affected patients might
- 89 -
not be diagnosed until adulthood. Approximately 50-70% of these
children have alopecia +/_ epidermal cysts.
Type 2B appears to result from over-expression of a hormone response
element-binding protein that interferes with the actions of 1,25-D.
Rx. Some patients respond to extremely high doses of vit D2, 25-D or
1,25-D, especially those without alopecia. Calcium doses also should be
high. Patients who do not respond to high-dose vitamin D may be
treated with long-term IV calcium, with possible transition to very high
dose oral calcium supplements.

❖ Chronic Renal Failure

CRF causes ↓ activity of 1α-hydroxylase in the kidney → ↓ production of

1,25-D. These patients also have hyperphosphatemia due to ↓ renal
excretion.
Rx. It requires use of activated form of vit D (1,25-D) which also can
suppress PTH (because PTH aggravate bone resorption to release
calcium). Because hyperphosphatemia is also a stimulus for PTH
secretion, serum phosphorus level also should be normalized by dietary
phosphorus restriction and oral phosphate binders.

Calcium Deficiency
Et. This form of rickets usually develops after weaning of children from
breast milk or formula, especially if occurs early & the weaning food
were deficient in dairy products (which are a good source of calcium) or
contain high level of phytate, oxalate, and phosphate, which decrease
absorption of dietary Ca. It also occur in patients with malabsorption
syndromes (here vit D also may be deficient) or in patients with
parenteral nutrition without adequate calcium.

C.M. It usually develop later than nutritional rickets (which usually

associated with breast-feeding) with classic signs and symptoms of
rickets, especially those related to hypocalcemia.

Inv. (see table above).

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 Rx. Provide adequate calcium, typically as a dietary supplement, doses
include: 700 (1-3 yr), 1,000 (4-8 yr), 1,300 (9-18 yr) mg/day of
elemental calcium. Vit D supplementation also may be necessary if there
is concurrent vit D deficiency.

Phosphorous Deficiency
❖ Inadequate Intake

Et. It is almost impossible to have a diet that is deficient in phosphorus,

except in starvation or severe anorexia. Malabsorption syndromes are
not only cause malabsorption of Pi, but also cause malabsorption of Ca &
vit D. Isolated malabsorption of Pi occurs mainly in patients on long-
term use of aluminum-containing antacids.

❖ Fibroblast Growth Factor–23 Disorders

FGF–23 is a humeral mediater that ↓ renal tubular reabsorption of Pi →

hypophosphatemia. It also ↓ the activity of renal 1α-hydroxylase → ↓
1,25-D level.
Increased levels of FGF-23 cause many of the phosphate-wasting
conditions that result in rickets as in the following disorders:-

• X-Linked Hypophosphatemic Rickets: It is the most common cause

of hypophosphatemic rickets. It also one of few disorders which are XL
dominant, i.e. affect the female carriers, although to a less extent.

Et. Mutation of the gene in this disorder cause ↑ levels of FGF–23 which
→ ↓ levels of Pi & 1,25-D.

C.M. Classical rickets, but abnormalities of the lower extremities and

poor growth are the dominant features. Some patients have
hypophosphatemia and short stature without clinically evident bone
disease.
Inv. (see table above).
Rx. Patients respond well to a combination of oral Pi (1-3 g/day of
elemental phosphorus ÷ 4-5 doses) and 1,25-D (30-70 ng/kg/day ÷ 2).
However, Cxs occur when there is no adequate balance between Pi
supplementation and calcitriol because excess Pi → ↓ Ca absorption

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 from gut → secondary hyperparathyroidism which worsen the bone
lesions. In contrast, excess calcitriol → hypercalciuria and
nephrocalcinosis and can even cause hypercalcemia.
Hence, monitor serum Ca, Pi, ALP, PTH, and urinary Ca, as well as
periodic renal US to evaluate nephrocalcinosis. Normalization of ALP
level is a useful method in assessing the therapeutic response.
For children with significant short stature, GH is an effective option,
whereas those with severe deformities may require surgery.
Burosumab-twza is a monoclonal antibody to FGF-23 that is an
approved alternative approach for treating XLH in children >1 yr.

• AD Hypophosphatemic Rickets: It is much less common than XLH. It

is due to mutation of the gene that prevent degradation of FGF-23 by
proteases → ↑ FGF–23 level.
C.M., Inv. & Rx. are the same as those of XLH.

• AR Hypophosphatemic Rickets: It is an extremely rare disorder

which is same as above; but it may be associated with arterial
calcification in infancy.

• Overproduction of FGF–23: Tumor-induced osteomalacia is more

common in adults than in children, where it can produce classic
rachitic findings. Most tumors are mesenchymal in origin and are
usually benign, small, and located in bone which secrete a number of
different putative FGF–23s. Rx by excision of the tumor, otherwise it is
same as that of XLHR.
Overproduction of FGF–23 also may be associated with Mccune-
Albright synd, Epidermal nevus synd, Raine synd & rarely
Neurofibromatosis. Rx by excision of these lesions (if feasible),
otherwise it is same as that of XLHR. Bisphosphonate may ↓ pain and
fracture risk associated with bone lesions of Mccune-Albright synd.

❖ Hereditary Hypophosphatemic Rickets with Hypercalciuria

This rare AR disorder is mainly described in the Middle East. It is due to

mutations in the gene for a sodium-phosphate co-transporter in the
proximal renal tubule → phosphate leak → hypophosphatemia → ↑

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1,25-D → ↑ intestinal absorption of Ca & suppression of PTH →
Hypercalciuria due to high absorption of Ca & low PTH (which normally
decreases renal excretion of Ca).

C.M. The dominant symptoms are rachitic leg abnormalities with short
stature, muscle weakness, bone pain and renal stones. However, the
severity of disease is variable in the same family.
Inv. (see table above).

Rx. Excellent response to oral phosphate replacement, 1-2.5 g/day ÷ 5.

Syndromes & Diseases associated with Rickets

Fanconi syndrome: It is one of the most important causes of proximal
RTA that → renal losses of phosphate, amino acids, bicarbonate,
glucose, urate, and other molecules that are normally reabsorbed in the
proximal tubule. The most clinically relevant consequences are rickets
as a result of hypophosphatemia as well as rickets is exacerbated by
chronic metabolic acidosis which causes bone dissolution. FTT is a
consequence of both rickets and RTA.
Rx. Bicarbonate (high dose) with phosphate replacement.

Dent disease: It is XL disorder caused by mutations in the gene

encoding chloride channel which expressed in the kidney. Affected
males have variable manifestations including; hematuria,
nephrolithiasis, nephrocalcinosis, CRF, and rickets which occurs in ≈
25% of patients.
Rx. Oral phosphate +/_ 1,25-D.

Distal RTA: It usually manifests with metabolic acidosis, FTT,

hypercalciuria, nephrocalcinosis, and rickets, which is variable.
Rx. Bicarbonate replacement +/_ Thiazide diuretic.

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 HYPERVITAMINOSIS D
(Vitamin D Intoxication)
Et. It is usually due to excessive intake of vit D either acutely
(accidentally) or long-term ingestion.
Note: The recommended upper limits for long-term daily vit D intake are
1,000 IU for children <1 yr & 2,000 IU for older children & adults.
C.M. Manifestations are due to hypercalcemia which is mainly due to
excessive bone resorption! & less by ↑ intestinal absorption of Ca:-
• GIT; nausea, vomiting, poor feeding, constipation, abdominal pain, and
pancreatitis.
• CVS; hypertension, ↓ Q-T interval, and arrhythmias.
• CNS; lethargy, hypotonia, confusion, disorientation, depression,
psychosis, hallucinations, and coma.
• Renal; polyuria, hypernatremia, ARF, nephrolithiasis, and
nephrocalcinosis (which may cause CRF).
Note: Dehydration is due to polyuria (from nephrogenic diabetes insipidus),
poor oral intake, and vomiting.
Inv. Hypercalcemia, extremely elevated levels of 25-D, but, surprisingly,
levels of 1,25-D are usually normal. Hyperphosphatemia is also
common, PTH levels are appropriately low with hypercalciuria. Renal
US may show nephrocalcinosis. Anemia is sometimes present.
D.Dx. Hyperparathyroidism, Williams syndrome, subcutaneous fat
necrosis, benign hypocalciuric hypercalcemia, & malignancy. High
intake of Ca can cause hypercalcemia, especially in renal insufficiency.
Rx.
• Rehydration by aggressive therapy with NS will lower serum Ca, often
with loop diuretic (e.g. furosemide) to further ↑ Ca excretion.
• Glucocorticoids e.g. prednisone 1-2 mg/kg/24 hr can ↓ intestinal
absorption of Ca by blocking the action of 1,25-D and also lower the
levels of 25-D and 1,25-D.
• Calcitonin or Bisphosphonates can inhibit bone resorption.
• Hemodialysis can rapidly lower serum Ca in patients with severe
hypercalcemia.
Pg. Most children make full recovery; however, hypervitaminosis D can
cause CRF or even death (due to arrhythmias or dehydration). Because
vit D is stored in fat, levels can remain elevated for months.

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