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Paediatric Biochemistry > Disorders of Calcium & Bone > Flashcards

Disorders of Calcium & Bone Flashcards

1
Q

What are biochemical tests used in a Child with serum Ca < 2.2 mmol/l?

A

SERUM

  • Calcium [Ca]
  • Phosphate [P]
  • Magnesium [Mg]: Always measure serum magnesium in hypocalcaemia child. The low serum magnesium can impair PTH secretion and can lead to restance of the action of PTH (bone & kidney)
  • Parathyroid hormone [PTH]
  • 25-hydroxyvitamin D [25OHD]
  • 1,25-dihydroxvitamin D [1,25(OH)2D]

URINE

  • Calcium/Creatinine ratio
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1
Q

How is Srum Calcium Concentration regulated by PTH?

A
  • Low calcium is sensed by the calcium sensing receptor in the parathyroid cell
  • PTH leads to increased calcium reabsorption in kidneys and phosphate excretion
  • PTH also activates 1α Hydroxylase which leads to calcitriol activation from 25 hydroxyvitamin D. The Calcitriol leads to increased dietary calcium absorption and phosphate absorption
  • This leads to maintenance of the serum calcium and this acts on the calcium sensing receptor which leads calcium absorption. Activation of PTH is then switched off.
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2
Q

What are symptoms of Hypocalcaemia?

A
  • Tingling sensation around the mouth & digits
  • Muscle cramps
  • Tetany
  • Focal or Generalised Fits
  • Laryngospasm & stridor
  • Apnoea
  • Cardiac Rhythm disturbance
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3
Q

What are causes of Low Serum Calcium?

A
  • Lab Error
  • Low Albumin
  • Is serum Magnesium Normal
  • Familial Hypocalcaemic Hypercalciuria
  • Hypoparathyroidism
  • Pseudo-hypoparathyroidism
  • Severe Vitamin D Deficiency or Vitamin D Dependent Rickets Type 1 or 2
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4
Q

What are biochemical results for Hypoparathyroidism?

A
  • PTH [Low/Undetectable]
  • 25-hydroxyvitamin D [Normal]
  • 1,25-dihydroxvitamin D [Low/Normal]
  • Calcium [LOW]
  • Phosphate [High]
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5
Q

What are biochemical results for Pseudo-hypoparathyroidism?

A
  • PTH [High/Very High]
  • 25-hydroxyvitamin D [Normal]
  • 1,25-dihydroxvitamin D [Low/Normal]
  • Calcium [LOW]
  • Phosphate [High]
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6
Q

What are biochemical results for Early vitamin D deficiency?

A
  • 25(OH)D ↓
  • Ca [Low normal]
  • PTH ↑
  • P ↓
  • 1,25(OH)2D ↑
  • ALP ↑
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7
Q

What are biochemical results for Severe vitamin D deficiency?

A
  • 25(OH)D ↓ ↓
  • Ca ↓
  • PTH ↑ ↑
  • P ↓ ↓
  • 1,25-(OH)2D ↓
  • ALP ↑ ↑
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8
Q

What are biochemical results for Transient PTH resistance?

A
  • Ca ↓
  • P ↑
  • 25(OH)D ↓↓
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9
Q

How does Neonatal Hypocalcaemia develop?

A

EARLY: Usually transient - by day 3-4 of life

  • Infants of diabetic mothers
  • Perinatal asphyxia
  • Severe pre-eclampsia

LATE: Occurs after day 5 of life

  • Oral phosphate load, e.g feeding of unmodified Cows milk
  • Infants of hyperparathyroid mother
  • Severe Vitamin D deficient mothers
  • Hypomagnesaemia
  • Osteopetrosis
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10
Q

What are genetic causes of impaired synthesis or secretion of PTH?

A
  • DiGeorge Syndrome
  • Genetic mutations interfering with the production of PTH (autosomal dominant, autosomal recessive)
  • HDR Syndrome (hypoparathyroidism, deafness, renal anomaly) - GATA 3 mutation
  • Sanjad-Sakati or Kenny-Caffey syndromes - TBCE mutation
  • Mutations of the calcium-sensing receptor (CaSR) and related proteins (autosomal dominant hypocalcemia)
  • Mutations interfering with parathyroid gland development (X-linked), GCM1 mutation
  • Mitochondrial disorders (eg, MELAS Syndrome, Kearns Sayre syndrome, mitochondrial trifunctional protein deficiency)
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11
Q

What are autoimmune causes of Impaired synthesis or secretion of PTH?

A
  • Autoimmune polyglandular syndrome type 1 (APS1)
  • Parathyroid or thyroid gland surgery
  • Infiltration of parathyroid gland (eg, iron overload)
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12
Q

How is Severe symptomatic treatment of hypocalcaemia managed?

A
  • IV 10% Calcium Gluconate @ 0.11 mmol/kg (0.5 mls/kg – max 20 mls) over 10 minutes
  • Continuous IV infusion of Calcium Gluconate @ 0.1 mmol/kg (Max 8.8 mmols) over 24 hours
  • Oral Calcium Supplements @ 0.2 mmol/kg (Max 10 mmols or 400 mg Ca) 4 x a day
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13
Q

How is Hypo & Pseudohypoparathyroidism treated?

A
  • Aim to keep serum Ca between 2.0 to 2.2 mmol/l
  • Oral Calcium supplements
  • Active preparations of Vitamin D: Alfacalcidiol @ 50 ng/kg (Max ~2µg/day)
  • Monitoring: Urine Ca/Cr (<0.7), Renal Ultrasound Scan-yearly
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14
Q

What are symptoms of Hypercalcaemia?

A
  • Gastrointestinal symptoms: Nausea, anorexia, vomiting & weight loss
  • Renal symptoms: Nephrogenic diabetes like picture – dehydration. Nephrocalcinosis.
  • CNS & Musculoskeletal symptoms: Lethargy & muscle weakness. Older children may present with psychiatric symptoms.
  • Cardiac effects: Hypertension. Short QT interval
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15
Q

What are causes of High PTH related Hypercalcaemia?

A
  1. Neonatal Severe Primary Hyperparathyroidism (AR inactivating mutations of the CaSR)
    • Decreased urinary calcium
  2. Parathyroid adenoma (Sporadic, Familial (MEN, hyperparathyroid jaw sd)
    • Increased urinary calcium
  3. Parathyroid carcinoma
16
Q

What are causes of Normal PTH related Hypercalcaemia?

A

Familial Hypocalciuric Hypercalcaemia – inactivating mutations of CaSR

  • Decreased Urinary Calcium
17
Q

What are causes of Low PTH related Hypercalcaemia?

A
  1. Williams syndrome
  2. Idiopathic hypercalcaemia of infancy
  3. Vitamin D toxicity
  4. Increased 1,25(OH)D2 synthesis
  5. Subcutaneous fat necrosis
  6. Sarcoidosis, tuberculosis
    • Increased urinary calcium
    • Increased calcium absorption
    • Increased 1,25(OH)D2 synthesis
18
Q

How is Hypercalcaemia managed?

A
  • Hyperhydration
  • Low Calcium & Vitamin D free diet
  • Corticosteroids
  • Pamidronate infusion (x2)
  • Bisphosphonates
  • Cinacalcet
  • Parathroidectomy
  • Monitoring Urine Ca/Cr (<0.56) and renal ultrasound scan
19
Q

What is Osteogenesis Imperfecta?

A
  • OI is a condition of extreme fragility of the bones causing recurrent low-trauma fractures
  • OI is the most common cause of primary osteoporosis
  • Osteoporosis is defined as reduced bone mass for body size and presence of significant fractures
20
Q

What are features of Type 1 Collagen?

A
  • Predominant collagen in bones
  • Type 1 collagen is formed by two α 1 chains and one α 2 chain
  • α 1 chain is coded by COL1A1 gene, α 2 chains are coded by COL1A2 gene
  • Mutations in the gene leads to OI
21
Q

What is the classification system of Osteogenesis Imperfecta?

A

Sillence Classification

22
Q

What is the Sillence Classification of Osteogenesis Imperfecta?

A
  • Type I: Mild with blue/grey sclera (autosomal dominant)
  • Type II: Usually lethal (autosomal dominant)
  • Type III: multiple fractures with deformities of limbs & spine
  • Type IV: Intermediate between types I & III (autosomal dominant)
    • Iva: Normal teeth
    • IVb: Dentinogenesis Imperfecta
23
Q

What are Signs and Symptoms of Osteogenesis Imperfecta?

A
  • Thin & smooth skin
  • Blue/grey sclera
  • Wormian bones
  • Dentinogenesis imperfecta
  • Presenile deafness
24
Q

What is the investigation for Oesteogenesis Imperfecta?

A
  • No definitive biochemical or imaging marker for OI
  • X-ray
  • Bone Mineral Density Scans
  • MUTATIONS IN GENES CODING FOR TYPE I COLLAGEN: Molecular biology tests to look for mutations in COL1A1 and COL1A2 genes responsible for production of Type 1 collagen
25
Q

What does the X-ray show for Osteogenesis Imperfecta?

A
  • Generalised osteoporosis of axial and appendicular skeleton
  • Milder forms - Thin, slender bones with thin cortices
  • Severe forms - Broad, shortened long bones with multiple fractures complicated by hyperplastic callous formation
  • Skull X-ray for Wormian bones
  • Vertebral X-ray for crush fractures
26
Q

How do Bisphosphonates act?

A

Bisphosphonates are taken up by osteoclasts and cause apoptosis

  • Net effect: Reduced bone resorption and an increase in bone mineral density
  • Bisphosphonates, synthetic analogues of inorganic pyrophosphate, potently inhibit skeletal resorption by suppressing the recruitment and activity of osteoclasts and shortening their life span
27
Q

What are side effects of Bisphosphonates?

A
  • Acute phase reaction at the first IV infusion (influenza-like symptoms); Rx with paracetamol or ibuprofen
  • Hypocalcaemia (uncommon problem) after ~ 72 hrs from infusion
  • Bone pain: ↓ with subsequent use
  • Transient iritis and/or uveitis (uncommon)

Paediatric Biochemistry (31 decks)

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