Pediatrics
Final Professional MBBS — Pediatrics. Complete question bank: Long Questions (10 marks) and Short Notes (5 marks) across all 15 systems, with clinical pearls, drug doses, staging tables, mnemonics and key-point recaps.
DEFINITION
Type 1 diabetes mellitus (T1DM) is a chronic disorder of absolute insulin deficiency caused by autoimmune destruction of the pancreatic β-cells. It is the commonest form of diabetes in children and typically presents in childhood or adolescence.
PATHOGENESIS
- Genetic susceptibility (HLA-DR/DQ) plus an environmental trigger → T-cell-mediated autoimmune β-cell destruction.
- Islet autoantibodies (anti-GAD, IA-2, insulin, ZnT8) mark the process → progressive insulinopenia.
CLINICAL FEATURES
- Classic triad — polyuria, polydipsia and polyphagia — with weight loss and fatigue.
- Secondary nocturnal enuresis; recurrent infections (candidiasis).
- May present acutely in diabetic ketoacidosis (DKA).
DIAGNOSIS (ADA criteria)
- Fasting plasma glucose ≥ 126 mg/dL, OR random ≥ 200 mg/dL with symptoms, OR 2-h OGTT ≥ 200 mg/dL, OR HbA1c ≥ 6.5%.
- Supportive — ketonuria/ketonaemia, positive islet autoantibodies, low C-peptide.
MANAGEMENT OF T1DM
- Insulin is essential and lifelong — a basal-bolus (multiple daily injection) regimen or an insulin pump.
- Carbohydrate counting, healthy diet, and regular exercise.
- Self-monitoring of blood glucose (or continuous glucose monitoring); target HbA1c generally < 7–7.5%.
- Structured education of child and family — sick-day rules, hypoglycaemia recognition/treatment, injection technique.
DIABETIC KETOACIDOSIS (DKA)
DKA is defined by the triad of hyperglycaemia (> 200 mg/dL), ketosis/ketonaemia, and metabolic acidosis (pH < 7.3, bicarbonate < 15). It is precipitated by new-onset diabetes, infection, or missed insulin.
- Clinical — dehydration, Kussmaul (deep) breathing, acetone (fruity) breath, abdominal pain, vomiting, and altered sensorium.
- Management — careful fluid replacement, an insulin infusion, potassium replacement (total-body potassium is depleted), correction of the precipitant, and hourly monitoring.
- Fluids and glucose are corrected gradually to avoid the feared complication of cerebral oedema (the leading cause of DKA death in children).
COMPLICATIONS
- Acute — DKA and hypoglycaemia (from insulin); hyperosmolar states.
- Chronic (long-term glycaemic damage) — microvascular (retinopathy, nephropathy, neuropathy) and macrovascular disease; growth/pubertal delay and dyslipidaemia.
MANAGEMENT OF HYPOGLYCAEMIA
- Mild — 10–15 g fast-acting oral carbohydrate, repeat as needed.
- Severe (unconscious/fitting) — IM/SC glucagon or IV 10% dextrose 2–5 mL/kg; then a longer-acting snack.
MONITORING & LONG-TERM CARE
- HbA1c every 3 months; periodic screening for retinopathy, nephropathy (urine albumin), thyroid and coeliac disease.
- Growth, puberty, injection sites, and psychological wellbeing.
TYPE 1 vs TYPE 2 DIABETES (children)
Feature Type 1 Type 2 Mechanism Autoimmune insulin deficiency Insulin resistance ± relative deficiency Body habitus Usually lean Usually obese; acanthosis nigricans Ketosis Common (DKA) Less common Autoantibodies Positive Negative Treatment Insulin (essential) Lifestyle ± metformin ± insulin THE 'HONEYMOON' PHASE
Soon after diagnosis and starting insulin, residual β-cell function may transiently reduce insulin needs (partial remission); families should be warned this is temporary and insulin must not be stopped.
INSULIN PREPARATIONS (overview)
- Rapid/short-acting (mealtime bolus) and long-acting/basal insulins are combined in a basal-bolus regimen.
- Doses are individualised and adjusted for food, activity and illness; pumps deliver continuous basal + boluses.
💊KEY DRUG DOSES (viva)- Insulin infusion 0.05–0.1 units/kg/hour (start AFTER initial fluids; no bolus in children).
- Fluids — correct deficit slowly over 24–48 h; initial bolus 10 mL/kg 0.9% saline only for shock.
- Potassium 20–40 mmol/L in fluids once urine output confirmed and K not high.
- Add dextrose to fluids when glucose falls to ~250–300 mg/dL to allow continued insulin.
⚠️DANGER / REMEMBER: Cerebral oedema — suspect with headache, falling consciousness, bradycardia or a rising blood pressure during treatment; give hypertonic saline/mannitol and slow the fluids. Avoid overly rapid correction of glucose and osmolality.📝CLINICAL / APPLIED POINTS- Any child with polyuria, polydipsia and weight loss needs a glucose check — don't miss new-onset diabetes.
- In DKA, give fluids first, then start insulin; never bolus insulin in children.
- Potassium looks normal/high initially but total body is depleted — replace early once urine flows.
- Correct glucose and fluids slowly — cerebral oedema is the killer.
- Education and sick-day rules prevent recurrent DKA admissions.
🔑KEY POINTS TO REMEMBER- Autoimmune β-cell destruction → absolute insulin deficiency; islet antibodies.
- Polyuria, polydipsia, polyphagia, weight loss; may present as DKA.
- Diagnose by ADA glucose/HbA1c criteria; lifelong insulin + monitoring + education.
- DKA = hyperglycaemia + ketosis + acidosis; fluids → insulin infusion → potassium.
- Cerebral oedema is the leading cause of DKA death — correct slowly.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics; ISPAD/ADA guidelines.DEFINITION
Congenital hypothyroidism is deficiency of thyroid hormone present from birth. It is one of the commonest preventable causes of intellectual disability — early detection and treatment give a normal outcome, whereas delay causes irreversible brain damage.
ETIOLOGY
- Thyroid dysgenesis (agenesis, hypoplasia, or an ectopic gland) — the commonest cause.
- Dyshormonogenesis — inherited (autosomal recessive) defects of hormone synthesis (may cause a goitre).
- Central (hypothalamic-pituitary) hypothyroidism; and transient causes (maternal antithyroid drugs, iodine deficiency/excess, maternal antibodies).
CLINICAL FEATURES (often subtle at birth)
- Prolonged neonatal jaundice, constipation, feeding difficulty, lethargy and a hoarse cry.
- Large posterior fontanelle, umbilical hernia, macroglossia, hypotonia, dry skin and coarse facies.
- If untreated → cretinism — severe growth failure and intellectual disability.
NEWBORN SCREENING (the key to prevention)
- Screening TSH (± T4) on a heel-prick/cord sample around day 3–5 — before symptoms appear.
- A raised screening TSH prompts urgent confirmatory testing and immediate treatment.
INVESTIGATIONS
- High TSH with low T4/free T4 (primary hypothyroidism).
- Thyroid ultrasound / radionuclide scan to determine the cause (dysgenesis vs ectopic vs dyshormonogenesis).
- X-ray — delayed bone age (absent distal femoral epiphysis at term).
MANAGEMENT
- Levothyroxine, started as early as possible (ideally within the first 2 weeks) — the earlier, the better the neurodevelopmental outcome.
- Monitor TSH and free T4 regularly and adjust the dose with growth; treatment is usually lifelong (transient causes are re-evaluated later).
- Developmental follow-up.
TRANSIENT CONGENITAL HYPOTHYROIDISM
- Caused by maternal antithyroid drugs, iodine deficiency or excess, or transplacental TSH-receptor-blocking antibodies.
- Requires treatment initially, then re-evaluation off therapy (usually after ~3 years) to confirm whether it is permanent.
DIFFERENTIAL / ASSOCIATED
- Distinguish primary (high TSH) from central (low/normal TSH with low T4) hypothyroidism.
- Down syndrome and other conditions carry a higher risk — have a low threshold for testing.
WHY EARLY TREATMENT IS CRITICAL
Thyroid hormone is essential for brain myelination and development in the first years of life; the therapeutic window is narrow, so treatment delayed beyond a few weeks risks permanent, irreversible intellectual impairment despite later normal hormone levels.
BONE AGE & 'CRETINISM'
- Bone age is delayed; untreated congenital hypothyroidism causes cretinism — severe intellectual disability with coarse features and stunting.
- Endemic (iodine-deficiency) cretinism has neurological and myxoedematous forms.
KEY EXAM POINT
Because early signs are easily missed, the whole strategy rests on newborn screening and immediate levothyroxine — an inexpensive test and cheap tablet that prevent lifelong disability.
SUMMARY OF THE SCREENING PATHWAY
Newborn heel-prick TSH (day 3–5) → Raised TSH → urgent confirmatory serum TSH/free T4 → Start levothyroxine immediately (within 2 weeks) → Establish the cause (scan/USG); monitor and adjust
COMPLICATIONS OF UNTREATED DISEASE
- Irreversible intellectual disability and neurological deficits (deafness, spasticity, ataxia in endemic cretinism).
- Severe growth failure, delayed bone maturation and delayed puberty.
💊KEY DRUG DOSES (viva)- Levothyroxine 10–15 µg/kg/day orally (single morning dose), started urgently.
- Do not mix with soy/iron/calcium (impair absorption); titrate to keep free T4 in the upper-normal range and TSH normal.
PROGNOSIS
With early treatment (within the first 2 weeks), growth and intellectual development are normal. Delay in starting therapy leads to irreversible intellectual disability — which is exactly why newborn screening and prompt levothyroxine are so important.
📝CLINICAL / APPLIED POINTS- Clinical signs are subtle at birth — screening, not the examination, catches most cases.
- Prolonged neonatal jaundice with constipation and lethargy should prompt a thyroid check.
- Start levothyroxine immediately on a confirmed high TSH — every week of delay costs IQ points.
- Avoid giving levothyroxine with soy formula, iron or calcium (reduced absorption).
- Monitor and adjust the dose as the child grows; follow development.
🔑KEY POINTS TO REMEMBER- Commonest preventable cause of intellectual disability; usually thyroid dysgenesis.
- Subtle at birth: prolonged jaundice, constipation, hoarse cry, large fontanelle, macroglossia.
- Detected by newborn TSH screening; confirm with high TSH + low T4.
- Levothyroxine 10–15 µg/kg/day started within 2 weeks → normal outcome.
- Delay causes irreversible brain damage — screen and treat early.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics.DEFINITION
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders of adrenal steroid synthesis. About 90% are due to 21-hydroxylase deficiency, causing cortisol (± aldosterone) deficiency with androgen excess.
PATHOPHYSIOLOGY
Enzyme (21-hydroxylase) block → ↓ Cortisol → ↑ ACTH (loss of negative feedback) → Adrenal hyperplasia + precursors shunted to androgens → ± Aldosterone deficiency → salt wasting
CLINICAL TYPES
Type Features Classic salt-wasting Cortisol + aldosterone deficiency; salt-wasting crisis; virilised female genitalia Simple virilising Androgen excess/virilisation, no salt wasting Non-classic Milder, later — precocious puberty, hirsutism, acne CLINICAL FEATURES
- Females — ambiguous genitalia (clitoromegaly, labial fusion) at birth from prenatal androgen exposure.
- Males — normal genitalia at birth (may be missed) and can present in a salt-wasting crisis.
- Salt-wasting crisis (usually 1st–2nd week) — vomiting, poor feeding, dehydration, shock, with hyponatraemia and hyperkalaemia.
- Later — rapid growth with advanced bone age and precocious puberty (androgen excess).
INVESTIGATIONS
- Markedly raised 17-hydroxyprogesterone (the key diagnostic test).
- Electrolytes — low sodium, high potassium (salt-wasting); low glucose.
- Raised ACTH and adrenal androgens; karyotype and pelvic ultrasound for sex assignment; newborn screening (17-OHP) where available.
MANAGEMENT
- Glucocorticoid replacement (hydrocortisone) — replaces cortisol and suppresses ACTH/androgen excess.
- Mineralocorticoid (fludrocortisone) + salt supplements in salt-wasting forms.
- Stress dosing (double/triple glucocorticoid during illness/surgery) to prevent adrenal crisis.
- Surgical correction of genitalia and psychological/genetic counselling; monitor growth and bone age.
OTHER ENZYME DEFECTS (besides 21-hydroxylase)
- 11β-hydroxylase deficiency — virilisation WITH hypertension (excess deoxycorticosterone).
- 17α-hydroxylase deficiency — hypertension with under-virilisation.
NEWBORN SCREENING & PRENATAL ISSUES
- Screening (17-OHP) allows pre-symptomatic detection and prevents salt-wasting crises.
- Prenatal diagnosis/therapy is possible in known-risk families (specialist-directed).
GROWTH & LONG-TERM MONITORING
- Balance is needed — under-treatment allows androgen excess (advanced bone age, poor final height); over-treatment (Cushingoid) impairs growth.
- Monitor growth velocity, bone age, blood pressure, electrolytes and androgen markers.
DIFFERENTIAL OF THE VIRILISED/AMBIGUOUS NEONATE
- Other 46,XX DSD (maternal androgens), 46,XY DSD, and syndromic causes.
- CAH is the commonest and the one that is immediately dangerous (salt-wasting) — exclude it first.
KEY EXAM POINT
Remember the two emergencies of CAH: the salt-wasting crisis (treat with saline, dextrose, hydrocortisone) and the psychosocial emergency of ambiguous genitalia (no hasty sex assignment); lifelong steroid replacement with stress dosing is the mainstay.
PROGNOSIS & FOLLOW-UP
With reliable glucocorticoid/mineralocorticoid replacement, stress dosing and monitoring of growth and bone age, children with CAH grow and develop well; adherence and prompt sick-day/crisis management are the keys to preventing life-threatening adrenal crises.
💊KEY DRUG DOSES (viva)- Hydrocortisone 10–15 mg/m²/day in 3 divided doses (maintenance).
- Fludrocortisone 0.05–0.2 mg/day (usually ~0.1 mg) + oral salt in infancy.
- Adrenal crisis: IV hydrocortisone 25–100 mg (bolus, by age) + 0.9% saline + 10% dextrose; treat hyperkalaemia.
⚠️DANGER / REMEMBER: Salt-wasting crisis is a life-threatening emergency — a vomiting, dehydrated, shocked neonate with hyponatraemia and hyperkalaemia needs immediate IV saline, dextrose and stress-dose hydrocortisone; do not wait for confirmatory results.📝CLINICAL / APPLIED POINTS- Any newborn girl with ambiguous genitalia — think CAH and check 17-OHP and electrolytes urgently.
- A vomiting, dehydrated male neonate in the 2nd week with low Na/high K may be in a salt-wasting crisis.
- 17-hydroxyprogesterone is the diagnostic test; salt-wasting shows hyponatraemia + hyperkalaemia.
- Teach families stress dosing and give an emergency plan to prevent adrenal crisis.
- Never assign sex hastily — karyotype and a multidisciplinary team guide management.
🔑KEY POINTS TO REMEMBER- Autosomal recessive; 90% 21-hydroxylase deficiency → low cortisol/aldosterone + androgen excess.
- Females: ambiguous genitalia; males: normal genitalia (may present in crisis).
- Salt-wasting crisis (week 1–2): vomiting, shock, low Na, high K.
- Raised 17-OHP is diagnostic; treat with hydrocortisone + fludrocortisone + salt.
- Stress dosing prevents adrenal crisis; salt-wasting crisis is an emergency.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics.DEFINITION
Precocious puberty is the appearance of secondary sexual characteristics before 8 years in girls and before 9 years in boys. It is classified by whether the hypothalamic-pituitary-gonadal (HPG) axis is activated.
CLASSIFICATION
Type Mechanism Common causes Central (true, GnRH-dependent) Early activation of the HPG axis Idiopathic (commonest in girls), CNS lesions/tumours, post-infection/irradiation Peripheral (pseudo, GnRH-independent) Sex steroids from outside the axis CAH, adrenal/gonadal tumours, McCune-Albright syndrome, exogenous steroids, hCG-secreting tumours NORMAL VARIANTS (to recognise and reassure)
- Premature thelarche — isolated early breast development, no other progression.
- Premature adrenarche — early pubic/axillary hair without other pubertal signs.
- These are usually benign and non-progressive.
CLINICAL EVALUATION
- History and Tanner staging; documentation of the sequence and tempo of changes.
- Growth assessment and bone age (typically advanced in true precocity).
- Look for CNS symptoms (headache, visual changes), café-au-lait macules (McCune-Albright/NF1), and virilising features.
INVESTIGATIONS
- GnRH (LHRH) stimulation test — a pubertal LH response indicates central precocity.
- Basal LH/FSH, oestradiol/testosterone; 17-OHP and adrenal androgens (for CAH/adrenal cause).
- MRI brain (central, especially boys and young girls) and pelvic/adrenal ultrasound; thyroid function; bone-age X-ray.
MANAGEMENT
- Central precocious puberty — GnRH analogues (e.g. leuprolide) to halt progression and preserve final height; treat any underlying CNS cause.
- Peripheral precocious puberty — treat the specific cause (surgery for tumours, glucocorticoids for CAH, specific agents for McCune-Albright).
- Psychological support for the child and family.
NORMAL PUBERTAL SEQUENCE (for reference)
- Girls: thelarche (breast) → pubarche → growth spurt → menarche.
- Boys: testicular enlargement (first sign, > 4 mL) → pubarche → penile growth → growth spurt.
CONSEQUENCES OF UNTREATED PRECOCITY
- Early rapid growth but premature epiphyseal fusion → short final adult height.
- Psychosocial/behavioural difficulties from a body-mind mismatch.
McCUNE-ALBRIGHT SYNDROME
A cause of peripheral precocious puberty featuring the triad of polyostotic fibrous dysplasia, café-au-lait macules (irregular 'coast of Maine' borders) and autonomous endocrine hyperfunction (precocious puberty).
INVESTIGATION SUMMARY
Test Purpose Bone age Advanced in true precocity GnRH stimulation Pubertal LH → central MRI brain CNS cause (esp. boys) 17-OHP / androgens CAH / adrenal cause Pelvic/adrenal USG Cyst/tumour KEY EXAM POINT
Two rules of thumb — precocious puberty in a boy is organic until proven otherwise (image the brain), and advanced bone age warns of compromised final height (a reason to treat central precocity with GnRH analogues).
PREMATURE THELARCHE vs TRUE PRECOCITY
Feature Premature thelarche True precocious puberty Other pubertal signs Absent Present (pubarche, growth spurt) Growth velocity Normal Accelerated Bone age Normal Advanced Progression None/regresses Progressive PROGNOSIS
Treated central precocious puberty (GnRH analogues) halts progression and protects final adult height; outcome in peripheral precocity depends on the underlying cause. Psychological support helps the child cope with being physically out of step with peers.
💊KEY DRUG DOSES (viva)- GnRH analogue — e.g. leuprolide depot (monthly/3-monthly) for central precocious puberty.
- Cause-specific: hydrocortisone (CAH), aromatase inhibitors/others (McCune-Albright).
📝CLINICAL / APPLIED POINTS- Define whether puberty is central (axis-driven) or peripheral — the GnRH test and bone age guide this.
- In boys, precocious puberty is more often organic (CNS) — image the brain.
- Advanced bone age warns of compromised final height — a reason to treat central precocity.
- Isolated thelarche/adrenarche are usually benign variants needing reassurance and follow-up.
- Always consider CAH and intracranial pathology before labelling it idiopathic.
🔑KEY POINTS TO REMEMBER- Secondary sexual characteristics before 8 (girls)/9 (boys).
- Central (GnRH-dependent; idiopathic commonest in girls) vs peripheral (GnRH-independent; CAH, tumours, McCune-Albright).
- Evaluate with Tanner staging, bone age, GnRH test, hormones, MRI/USG.
- Central → GnRH analogues; peripheral → treat the cause.
- Boys and very young girls need brain imaging (higher chance of organic cause).
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics.DEFINITION
Inborn errors of metabolism (IEM) are inherited (mostly autosomal recessive) defects of enzymes/transporters in metabolic pathways, leading to accumulation of toxic substrates, deficiency of products, or energy failure. Individually rare but collectively important and often treatable if recognised early.
WHEN TO SUSPECT AN IEM
- A previously well neonate who deteriorates after a symptom-free interval with encephalopathy, poor feeding, vomiting and lethargy (a 'sepsis-like' picture with negative cultures).
- Unexplained metabolic acidosis, hypoglycaemia, or hyperammonaemia.
- Developmental regression, recurrent unexplained illness, an unusual odour, cataracts, hepatomegaly, or coarse features.
- Consanguinity, a family history, or unexplained sibling/neonatal deaths.
BROAD CATEGORIES
Group Examples Carbohydrate Galactosaemia, glycogen storage disease Amino acid Phenylketonuria, maple syrup urine disease Organic acidaemias Methylmalonic, propionic acidaemia Urea cycle defects Hyperammonaemia Fatty acid oxidation MCAD deficiency (hypoketotic hypoglycaemia) Lysosomal / mitochondrial Storage disorders; energy defects CLINICAL CLUES BY BIOCHEMISTRY
- High anion-gap metabolic acidosis → organic acidaemias.
- Hyperammonaemia without acidosis → urea cycle defects.
- Hypoglycaemia (± hepatomegaly) → glycogen storage/fatty acid oxidation disorders.
- Reducing substances / cataracts / E. coli sepsis → galactosaemia.
INVESTIGATIONS
- First-line ('metabolic screen') — blood gas, glucose, ammonia, lactate, ketones, electrolytes, and urine for ketones/reducing substances.
- Specific — tandem mass spectrometry (TMS), urine organic acids, plasma amino acids, and specific enzyme/genetic assays.
- Newborn screening detects several treatable IEMs pre-symptomatically.
MANAGEMENT — Principles
- Acute: stop the offending feed, give IV dextrose to reverse catabolism, correct acidosis, and lower ammonia (scavengers/dialysis) as needed.
- Specific: substrate restriction (special diets), cofactor/vitamin supplementation, and replacement of deficient products.
- Long-term: avoid fasting, sick-day plans, dietician/metabolic specialist follow-up, and genetic counselling.
ACUTE STABILISATION (the metabolic emergency)
Stop protein/offending feeds → IV 10% dextrose to reverse catabolism → Correct acidosis and dehydration → Lower ammonia (scavengers ± dialysis) if hyperammonaemic → Start specific therapy once the diagnosis is clarified
ILLUSTRATIVE EXAMPLES
- Maple syrup urine disease — encephalopathy + maple-syrup-smelling urine (branched-chain amino acids).
- Organic acidaemias — high-anion-gap acidosis with ketosis; urea cycle defects — hyperammonaemia without acidosis.
PROGNOSIS & COUNSELLING
Outcome depends on the specific disorder and how early it is treated; several are highly treatable with diet/cofactors. Genetic counselling, carrier testing and (where available) prenatal diagnosis are offered, especially with consanguinity or a previous affected child.
INHERITANCE & PREVENTION
- Most IEMs are autosomal recessive (some X-linked/mitochondrial); consanguinity increases risk.
- Expanded newborn screening detects several treatable disorders before symptoms; prenatal diagnosis is possible in known-risk families.
KEY EXAM POINT
The lifesaving reflex is: a deteriorating neonate with encephalopathy and a metabolic derangement (acidosis / hypoglycaemia / hyperammonaemia) → send the metabolic screen and start IV dextrose immediately, then seek specific therapy.
ROLE OF THE METABOLIC TEAM
Confirmed IEMs are managed with a metabolic specialist and dietitian — tailored diets, cofactor/vitamin therapy, emergency regimens for intercurrent illness, and long-term developmental follow-up, alongside family genetic counselling.
📝CLINICAL / APPLIED POINTS- Think IEM in a term baby who was well, then collapsed with encephalopathy and negative cultures.
- Send the metabolic screen (gas, glucose, ammonia, lactate, ketones) BEFORE giving blood products or feeds where possible.
- IV dextrose to stop catabolism is a safe, immediate first step while awaiting results.
- Ask about consanguinity and prior sibling deaths — strong pointers to a recessive IEM.
- Many IEMs are treatable — early recognition can be lifesaving and prevent disability.
🔑KEY POINTS TO REMEMBER- Inherited (mostly AR) enzyme defects → toxic accumulation / deficiency / energy failure.
- Suspect: well neonate then encephalopathy/acidosis/hypoglycaemia/hyperammonaemia; regression; consanguinity.
- Screen: gas, glucose, ammonia, lactate, ketones; then TMS, urine organic acids, amino acids.
- Acute: stop feeds, IV dextrose, correct acidosis, lower ammonia; specific diets/cofactors long-term.
- Many are treatable — recognise early; genetic counselling for the family.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics.DEFINITION
Diabetes insipidus (DI) is the passage of large volumes of dilute urine due to either deficiency of antidiuretic hormone (ADH/vasopressin) — central DI — or renal resistance to ADH — nephrogenic DI.
TYPES & CAUSES
Type Mechanism Causes Central ↓ ADH secretion Tumours, trauma, surgery, infiltration, idiopathic Nephrogenic Renal resistance to ADH X-linked/genetic, hypokalaemia, hypercalcaemia, drugs, obstruction CLINICAL FEATURES
- Polyuria and polydipsia with a craving for water; nocturia/enuresis.
- Risk of hypernatraemic dehydration if fluid access is limited (especially in infants).
INVESTIGATIONS & MANAGEMENT
- Dilute urine (low osmolality) despite raised/normal serum osmolality; water deprivation test with a desmopressin response distinguishes central from nephrogenic.
- Central DI — desmopressin (DDAVP).
- Nephrogenic DI — treat the cause, ensure water access, low-solute diet, and thiazide diuretics (± amiloride/indomethacin).
DIFFERENTIAL DIAGNOSIS
- Primary polydipsia (psychogenic water drinking) — dilute urine but low/normal serum sodium.
- Osmotic diuresis (diabetes mellitus), hypercalcaemia, hypokalaemia.
KEY EXAM POINT
The water-deprivation test with a subsequent desmopressin challenge is the crux: urine concentrates after desmopressin in central DI but not in nephrogenic DI. Beware hypernatraemic dehydration in infants who cannot ask for water.
COMPLICATIONS & MONITORING
- Hypernatraemic dehydration is the main danger, especially in infants and during illness/limited fluid access.
- On desmopressin, avoid over-treatment (hyponatraemia); educate families on fluid balance and sick-day care.
KEY EXAM POINT
Polyuria with dilute urine despite a high/normal serum sodium is the clue to diabetes insipidus; the desmopressin response then separates central (responds) from nephrogenic (does not) forms.
🔑KEY POINTS TO REMEMBER- Large volumes of dilute urine — central (↓ADH) or nephrogenic (ADH resistance).
- Polyuria, polydipsia; risk of hypernatraemic dehydration.
- Water deprivation + desmopressin response separates the two types.
- Central: desmopressin; nephrogenic: treat cause, thiazides, water access.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics.DEFINITION
Phenylketonuria (PKU) is an autosomal recessive inborn error caused by deficiency of phenylalanine hydroxylase, leading to accumulation of phenylalanine, which is toxic to the developing brain.
CLINICAL FEATURES
- Normal at birth; if untreated → progressive intellectual disability, seizures and behavioural problems.
- Fair skin and hair, blue eyes (reduced melanin), eczema, and a characteristic musty/'mousy' odour.
DIAGNOSIS & MANAGEMENT
- Newborn screening (Guthrie test / tandem mass spectrometry) detects raised phenylalanine before damage occurs.
- Lifelong low-phenylalanine diet (special formula; restrict protein), started early — this prevents intellectual disability.
- Avoid aspartame (a phenylalanine source); maternal PKU control in pregnancy protects the fetus.
PATHOPHYSIOLOGY
Without phenylalanine hydroxylase, phenylalanine cannot be converted to tyrosine; it accumulates and its metabolites (phenylketones) are neurotoxic, while reduced tyrosine (and hence melanin) explains the fair colouring.
MATERNAL PKU
A mother with poorly controlled PKU exposes her fetus to high phenylalanine, causing microcephaly, congenital heart disease and intellectual disability — so strict dietary control is essential before and during pregnancy.
MONITORING & PROGNOSIS
Blood phenylalanine levels are monitored and kept within target by dietary adjustment. With early, well-controlled treatment, intelligence and development are normal; late or poor control leads to irreversible intellectual disability.
VARIANTS
Milder hyperphenylalaninaemia and BH4 (tetrahydrobiopterin) cofactor defects exist; the latter need cofactor and neurotransmitter treatment, not just diet — hence confirmatory testing after a positive screen.
KEY EXAM POINT
PKU is the classic 'treatable' newborn-screening condition — a simple diet started early prevents severe intellectual disability, illustrating why screening programmes matter.
PREVENTION AT POPULATION LEVEL
Universal newborn screening for PKU, with prompt dietary treatment of detected cases, is a cost-effective public-health measure that prevents an otherwise devastating but avoidable intellectual disability.
🔑KEY POINTS TO REMEMBER- AR deficiency of phenylalanine hydroxylase → phenylalanine accumulation (brain-toxic).
- Untreated: intellectual disability, seizures, fair skin/hair, musty odour.
- Detected by newborn screening (Guthrie/TMS).
- Early lifelong low-phenylalanine diet prevents disability; avoid aspartame.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics.DEFINITION
Galactosaemia is an autosomal recessive disorder, classically due to deficiency of galactose-1-phosphate uridyltransferase (GALT), causing accumulation of galactose and its metabolites after milk (lactose) ingestion.
CLINICAL FEATURES
- Onset after starting milk feeds — vomiting, poor feeding, failure to thrive, and jaundice with hepatomegaly.
- Hypoglycaemia, cataracts, and a characteristic predisposition to E. coli sepsis.
- If untreated → liver failure and intellectual disability.
DIAGNOSIS & MANAGEMENT
- Reducing substances in urine (non-glucose), low GALT enzyme activity; newborn screening where available.
- Immediate, lifelong galactose/lactose-free diet — a soy-based (lactose-free) formula — which reverses the acute features.
- Monitor for cataracts and developmental progress.
PATHOPHYSIOLOGY & COMPLICATIONS
Accumulated galactose-1-phosphate is toxic to the liver, kidney and brain, and galactitol deposition in the lens causes cataracts. Early liver failure, bleeding and E. coli sepsis can be fatal in the neonatal period.
KEY EXAM POINT
A neonate who develops jaundice, hepatomegaly and poor feeding after starting milk — with urine positive for reducing substances but negative for glucose — should raise suspicion of galactosaemia; stop lactose immediately.
NEWBORN SCREENING & PROGNOSIS
Where newborn screening exists, galactosaemia is detected early and dietary treatment started before serious damage. Even with a strict diet, some long-term issues (learning difficulties, ovarian failure in girls) may occur, so follow-up is needed.
EMERGENCY IN THE NEONATE
A sick neonate with galactosaemia is prone to Gram-negative (E. coli) sepsis and liver failure; if suspected, stop lactose (switch to a soy/lactose-free formula) immediately while confirming the diagnosis, and treat sepsis.
KEY EXAM POINT
The triad of jaundice, hepatomegaly and cataracts in an infant unwell after milk, with urinary reducing substances, should trigger a lactose-free diet without delay.
🔑KEY POINTS TO REMEMBER- AR GALT deficiency → galactose accumulation after milk feeds.
- Vomiting, jaundice, hepatomegaly, hypoglycaemia, cataracts, E. coli sepsis.
- Urine reducing substances + low GALT; newborn screening.
- Lifelong galactose/lactose-free (soy) diet is the treatment.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics.DEFINITION
Acquired (juvenile) hypothyroidism is thyroid hormone deficiency developing after infancy. The commonest cause is autoimmune (Hashimoto) thyroiditis; iodine deficiency is important in endemic areas.
CLINICAL FEATURES
- Growth failure / short stature with delayed bone age (a key paediatric clue) — often with a relatively good weight.
- Lethargy, cold intolerance, constipation, dry skin, and poor school performance.
- Goitre; delayed (occasionally precocious) puberty.
INVESTIGATIONS & MANAGEMENT
- High TSH with low free T4 (primary); anti-thyroid peroxidase (anti-TPO) antibodies in autoimmune thyroiditis.
- Levothyroxine replacement, titrated to normalise TSH; monitor growth and puberty.
COMPLICATIONS IF UNTREATED
- Persistent growth failure and short stature; delayed puberty and poor academic performance.
- Rarely, myxoedema; a large goitre may cause local symptoms.
KEY EXAM POINT
In a short child who is gaining weight with a delayed bone age and falling growth velocity, always check thyroid function — hypothyroidism is a readily treatable cause of growth failure.
INVESTIGATIONS & ASSOCIATIONS
- TSH, free T4 and anti-TPO antibodies; ultrasound if the goitre is nodular.
- Autoimmune thyroiditis may coexist with other autoimmune conditions (type 1 diabetes, coeliac disease) and with Down/Turner syndromes.
MECHANISM & GOITRE
In autoimmune (Hashimoto) thyroiditis, lymphocytic infiltration damages the gland; a compensatory rise in TSH may produce a goitre. In iodine-deficient areas, lack of substrate for hormone synthesis is the cause.
KEY EXAM POINT
The paediatric hallmark is growth failure with a delayed bone age but preserved/increased weight — a pattern that should always prompt thyroid testing, since replacement reverses it.
PROGNOSIS
Growth and pubertal development normalise with adequate levothyroxine replacement if started before prolonged deprivation; ongoing monitoring ensures the dose keeps pace with growth.
🔑KEY POINTS TO REMEMBER- Acquired hypothyroidism — commonest cause Hashimoto (autoimmune); iodine deficiency in endemic areas.
- Short stature with delayed bone age, lethargy, constipation, goitre, poor school performance.
- High TSH, low T4, positive anti-TPO.
- Treat with levothyroxine, titrated to TSH.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics.DEFINITION
Delayed puberty is the absence of secondary sexual characteristics by 13 years in girls and 14 years in boys (or failure to progress through puberty).
CAUSES
- Constitutional delay of growth and puberty — the commonest (a normal variant, often familial; delayed bone age).
- Hypogonadotropic hypogonadism (low LH/FSH) — chronic illness, malnutrition, hypothyroidism, Kallmann syndrome, pituitary disease.
- Hypergonadotropic hypogonadism (high LH/FSH — primary gonadal failure) — Turner syndrome (girls), Klinefelter syndrome (boys), gonadal damage.
EVALUATION & MANAGEMENT
- History, examination, bone age, LH/FSH (to separate the two hypogonadism groups), and karyotype where indicated.
- Constitutional delay — reassurance ± a short course of low-dose sex steroids.
- Treat the underlying cause; sex-steroid replacement for permanent hypogonadism.
FEATURES OF SPECIFIC CAUSES
- Turner syndrome (45,X) — short stature, webbed neck, widely spaced nipples, ovarian failure.
- Klinefelter syndrome (47,XXY) — tall, small firm testes, gynaecomastia, infertility.
- Kallmann syndrome — hypogonadotropic hypogonadism WITH anosmia.
KEY EXAM POINT
Bone age plus LH/FSH is the key branch point — a delayed bone age with low gonadotropins and a family history suggests benign constitutional delay, whereas high gonadotropins point to primary gonadal failure (do a karyotype).
MANAGEMENT DETAIL
- Constitutional delay — reassurance; a short course of low-dose testosterone (boys)/oestrogen (girls) can be offered for distress.
- Permanent hypogonadism — pubertal induction and maintenance with sex steroids; treat the underlying condition.
PATTERN RECOGNITION
- Short girl with delayed puberty → think Turner syndrome (karyotype).
- Tall boy with small testes → think Klinefelter syndrome.
- Delayed puberty with anosmia → Kallmann syndrome.
KEY EXAM POINT
Constitutional delay is a diagnosis of exclusion but the commonest cause — a well child with a delayed bone age and a family history of 'late bloomers' can usually be reassured after basic tests.
🔑KEY POINTS TO REMEMBER- No secondary sexual characteristics by 13 (girls)/14 (boys).
- Constitutional delay (commonest, normal variant) vs hypo-/hypergonadotropic hypogonadism.
- Bone age + LH/FSH + karyotype (Turner, Klinefelter) guide the cause.
- Reassurance ± short steroid course (constitutional); treat cause / replace steroids otherwise.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics.DEFINITION
Ambiguous genitalia describes external genitalia that are not clearly male or female. Disorders of sex development (DSD) is the umbrella term, classified using the karyotype.
CLASSIFICATION
Type Examples 46,XX DSD Congenital adrenal hyperplasia (commonest cause), maternal androgens 46,XY DSD Androgen insensitivity, testosterone synthesis/5α-reductase defects Sex-chromosome DSD Turner, Klinefelter, mixed gonadal dysgenesis APPROACH
- Do NOT assign or declare the sex hastily — this is a sensitive emergency needing a multidisciplinary team.
- Investigations — karyotype, 17-hydroxyprogesterone, serum electrolytes (exclude salt-wasting CAH), pelvic ultrasound and hormone profile.
- Exclude salt-wasting CAH urgently (life-threatening) — check electrolytes and 17-OHP.
- Sex of rearing is decided with the family after evaluation; provide counselling and support.
URGENT vs NON-URGENT
- Urgent: exclude salt-wasting CAH (electrolytes, 17-OHP) — it is life-threatening.
- Look for associated dysmorphism/anomalies that point to a syndrome.
KEY EXAM POINT
Ambiguous genitalia is both a medical and a social emergency — resist pressure to declare the sex immediately; investigate (karyotype, 17-OHP, electrolytes, imaging) and let a multidisciplinary team and the family decide the sex of rearing.
MANAGEMENT PRINCIPLES
- Multidisciplinary team (endocrinology, surgery, genetics, psychology); treat CAH; consider timing of any surgery carefully.
- Long-term hormone therapy and psychological support depending on the diagnosis and sex of rearing.
TIMING & SENSITIVITY
Genital ambiguity is distressing for families and socially urgent; a calm, honest explanation ('the development is incomplete and we need tests to guide the best decision') is important while investigations proceed.
KEY EXAM POINT
The two non-negotiables are: exclude salt-wasting CAH (life-threatening) and do not assign sex hastily — investigate and involve a specialist team and the family.
🔑KEY POINTS TO REMEMBER- Ambiguous genitalia = DSD; classify by karyotype (46,XX / 46,XY / sex-chromosome).
- CAH is the commonest cause of 46,XX DSD (and a salt-wasting emergency).
- Key tests: karyotype, 17-OHP, electrolytes, pelvic USG, hormones.
- Do not assign sex hastily; multidisciplinary team + family counselling.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics.DEFINITION
Glycogen storage diseases (GSDs) are inherited defects of glycogen metabolism. Type I (Von Gierke disease) is due to glucose-6-phosphatase deficiency (autosomal recessive), impairing the release of glucose from the liver.
CLINICAL FEATURES
- Fasting (ketotic) hypoglycaemia and its symptoms.
- Massive hepatomegaly and a protuberant abdomen; 'doll-like' facies; growth failure.
- Biochemical hallmarks — lactic acidosis, hyperuricaemia and hyperlipidaemia.
DIAGNOSIS & MANAGEMENT
- Suggestive biochemistry (fasting hypoglycaemia, lactic acidosis); confirmed by enzyme/genetic testing.
- Maintain normoglycaemia — frequent feeds and uncooked cornstarch, and avoid fasting (including overnight, via continuous feeds in infancy).
- Manage the metabolic complications (uric acid, lipids); dietary/metabolic follow-up.
OVERVIEW OF GSD TYPES
- Type I (Von Gierke) — glucose-6-phosphatase; liver + hypoglycaemia.
- Type II (Pompe) — acid maltase; cardiomyopathy and hypotonia.
- Type III/IV/V (McArdle) — liver/muscle variants.
KEY EXAM POINT
Suspect a hepatic GSD in an infant with a huge liver, doll-like facies and fasting hypoglycaemia with lactic acidosis; management centres on preventing hypoglycaemia with frequent feeds and cornstarch.
INVESTIGATIONS & FOLLOW-UP
- Fasting hypoglycaemia with lactic acidosis, hyperuricaemia and hyperlipidaemia; confirm by enzyme/molecular testing.
- Long-term monitoring for growth, hepatic adenomas, renal disease and metabolic control.
CLINICAL RECOGNITION
- Hepatic GSDs → hepatomegaly + fasting hypoglycaemia; muscle GSDs → exercise intolerance/cramps.
- Pompe (type II) is distinct — a lysosomal disease with cardiomegaly and hypotonia in infancy.
KEY EXAM POINT
The management principle across hepatic GSDs is the same — avoid fasting and maintain glucose (frequent feeds, cornstarch, overnight feeds in infants) — while treating the metabolic complications.
PROGNOSIS
With good metabolic control (avoiding hypoglycaemia), children with hepatic GSD grow and do well; long-term surveillance addresses complications such as hepatic adenomas and renal involvement in type I.
🔑KEY POINTS TO REMEMBER- Type I GSD (Von Gierke) — glucose-6-phosphatase deficiency (AR).
- Fasting hypoglycaemia, massive hepatomegaly, doll-like facies, growth failure.
- Lactic acidosis, hyperuricaemia, hyperlipidaemia.
- Treat with frequent feeds/cornstarch, avoid fasting; manage complications.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics.