📌 Metabolic Mnemonics & Diagnostic Blueprint

Nelson Textbook of Pediatrics — Screening tests, confirmatory diagnostics, most accurate treatments & easy mnemonics for inborn errors of metabolism (Ch 104–113).

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General IEM suspicion

🔍 Approach to IEM

🩸 SCREENING

Newborn screening by tandem mass spectrometry (NBS); urine ketones, reducing substances; blood ammonia, lactate, glucose, blood gas.

🎯 DIAGNOSTIC TESTS

Plasma amino acids, urine organic acids, acylcarnitine profile, lactate/pyruvate ratio, enzyme assays (leukocytes/fibroblasts).

✅ MOST ACCURATE TREATMENT

Emergency: IV glucose 10%, stop protein, IV carnitine, ammonia scavengers (benzoate/phenylacetate), hemodialysis if NH₃ >500 μmol/L.

🧠 Mnemonic (clinical clues): “VOMITS” – Vomiting + Odd odor + Metabolic acidosis + Intractable seizures + Tachypnea + Sepsis-like picture → think IEM.

Hyperammonemia DDx

🚨 Hyperammonemia

🩸 SCREENING

Plasma ammonia (stat), blood gas, plasma amino acids (citrulline), urine orotic acid.

🎯 DIAGNOSTIC TESTS

Plasma amino acids (low citrulline→OTC/CPS1, high citrulline→ASS), urine orotic acid (elevated in OTC), enzyme assays, genetic panels.

✅ MOST ACCURATE TREATMENT

IV sodium benzoate/phenylacetate, IV arginine, IV glucose, hemodialysis (NH₃ >500), protein restriction.

🧠 Mnemonic: “OTC is X-linked, low cit, high orotic; CPS1 low cit, NO orotic.”

🧬 PKU (PAH deficiency)

🩸 SCREENING

NBS: elevated Phe, Phe/Tyr ratio

🎯 DIAGNOSTIC TESTS

Plasma Phe & Tyr, PAH gene, BH4 loading test, urine pterins

✅ MOST ACCURATE TREATMENT

Low-Phe diet + Phe-free amino acid formula, sapropterin (BH4) if responsive, pegvaliase for adults

🧠 Mnemonic: “Phe no ‘Phe’unny: Low protein, keep mental sunny.”

🧬 MSUD (BCKDH def.)

🩸 SCREENING

NBS: elevated Leu, Ile, Val, alloisoleucine

🎯 DIAGNOSTIC TESTS

Plasma amino acids (alloisoleucine pathognomonic), urine ketoacids, BCKDHA/B/C gene

✅ MOST ACCURATE TREATMENT

Acute: hemodialysis, IV glucose, BCAA-free TPN; long-term: BCAA-restricted diet

🧠 Mnemonic: “Maple Syrup - Dialyze Quickly, Diet Low in Branched chains.”

🧬 Homocystinuria (CBS)

🩸 SCREENING

NBS: elevated methionine

🎯 DIAGNOSTIC TESTS

Plasma total homocysteine, methionine; CBS gene

✅ MOST ACCURATE TREATMENT

Pyridoxine (B6) responsive → high-dose B6; B6 non-responders: low-methionine diet, betaine, B12/folate

🧠 Mnemonic: “CBS → Clot, B6, Surgery (lens) + Stroke prevention.”

🧬 Urea cycle defects (OTC)

🩸 SCREENING

NBS limited; clinical ammonia + amino acids

🎯 DIAGNOSTIC TESTS

Plasma ammonia, amino acids (low citrulline), urine orotic acid, OTC sequencing

✅ MOST ACCURATE TREATMENT

IV sodium benzoate/phenylacetate, arginine, hemodialysis, liver transplantation for severe

🧠 Mnemonic: “OTC: Oranges (orotic acid) + low Citrulline.”

🧬 MCAD deficiency

🩸 SCREENING

NBS: elevated C8-carnitine, C8/C10 ratio

🎯 DIAGNOSTIC TESTS

Plasma acylcarnitine, ACADM gene, urine hexanoylglycine

✅ MOST ACCURATE TREATMENT

Avoid fasting, IV glucose during illness, carnitine, cornstarch (no long-chain fat restriction)

🧠 Mnemonic: “MCAD – Midnight Crisis, Avoid fasting, Dextrose rescue.”

🧬 Gaucher type 1

🩸 SCREENING

NBS enzyme activity (dried blood spot), also clinical

🎯 DIAGNOSTIC TESTS

Leukocyte glucocerebrosidase, GBA gene, bone marrow Gaucher cells

✅ MOST ACCURATE TREATMENT

ERT (imiglucerase), substrate reduction (miglustat/eliglustat)

🧠 Mnemonic: “Gaucher – Gaucher cells, Glucocerebroside, Grow spleen, Give ERT.”

🧬 X‑linked adrenoleukodystrophy

🩸 SCREENING

NBS: elevated C26:0, VLCFA ratio

🎯 DIAGNOSTIC TESTS

Plasma VLCFA (C26/C22, C24/C22), ABCD1 gene

✅ MOST ACCURATE TREATMENT

HSCT for early cerebral disease, adrenal replacement, monitoring MRI

🧠 Mnemonic: “ALD: Adrenal, Leukodystrophy, Demyelination, ABCD1.”

🧬 Tay–Sachs (GM2)

🩸 SCREENING

NBS (Hex A assay in some regions), carrier screening

🎯 DIAGNOSTIC TESTS

Leukocyte hexosaminidase A (HEXA gene), cherry-red spot exam

✅ MOST ACCURATE TREATMENT

Supportive only (no cure); prenatal diagnosis crucial

🧠 Mnemonic: “Tay-Sachs – Cherry-Red Spot, Startle, Ashkenazi Jewish.”

🍞 GSD I (von Gierke)

🩸 SCREENING

NBS not routine; clinical: hypoglycemia + hepatomegaly

🎯 DIAGNOSTIC TESTS

Glucose-6-phosphatase assay (liver), G6PC/SLC37A4 gene

✅ MOST ACCURATE TREATMENT

Uncooked cornstarch q4-6h, avoid fructose/galactose, frequent feeds

🧠 Mnemonic: “GSD I: Glucose-6-phosphatase, ‘I’ can’t make glucose, Liver huge, Lactic high.”

🍞 GSD III (Cori/Forbes)

🩸 SCREENING

Clinical: hepatomegaly, hypoglycemia, normal lactate/uric acid

🎯 DIAGNOSTIC TESTS

Debrancher enzyme (AGL), glucagon test (rise after meal), gene sequencing

✅ MOST ACCURATE TREATMENT

High-protein diet, cornstarch, avoid fasting

🧠 Mnemonic: “Type III: ‘III’ livers + muscles weak, but lactate normal.”

🍞 Galactosemia (GALT)

🩸 SCREENING

NBS: elevated galactose, low GALT enzyme

🎯 DIAGNOSTIC TESTS

Erythrocyte GALT activity, GALT gene, urine galactitol

✅ MOST ACCURATE TREATMENT

Lactose-free (soy) formula, lifelong galactose restriction, calcium/vitamin D

🧠 Mnemonic: “Galactosemia: GI, Liver, E. coli, Cataracts – ‘GLC’ Stop milk.”

🍞 HFI (Aldolase B)

🩸 SCREENING

Reducing substances in urine (after fructose intake)

🎯 DIAGNOSTIC TESTS

ALDOB gene, liver aldolase B activity, fructose challenge (avoid)

✅ MOST ACCURATE TREATMENT

Strict avoidance of fructose, sucrose, sorbitol

🧠 Mnemonic: “HFI: Hypoglycemia after Fruit, Intolerance, Avoid sweet.”

⚡ MELAS

🩸 SCREENING

Lactate, lactate/pyruvate ratio, clinical suspicion

🎯 DIAGNOSTIC TESTS

mtDNA sequencing (m.3243A>G), muscle biopsy (RRF), MRI stroke-like lesions

✅ MOST ACCURATE TREATMENT

IV arginine for acute stroke-like episodes, CoQ10, avoid valproate

🧠 Mnemonic: “MELAS: Mitochondrial, Encephalopathy, Lactic, Stroke, m.3243.”

⚡ Leigh syndrome

🩸 SCREENING

Lactic acidosis, basal ganglia MRI lesions

🎯 DIAGNOSTIC TESTS

CSF lactate, MRI (putamen/ brainstem), nuclear/mtDNA panels (SURF1, MT-ATP6)

✅ MOST ACCURATE TREATMENT

Supportive; thiamine, ketogenic diet (if PDH deficiency), CoQ10

🧠 Mnemonic: “Leigh = Symmetrical lesions, high Lactate, basal ganglia.”

🧪 Hurler (MPS I-H)

🩸 SCREENING

NBS: enzyme assay (α-L-iduronidase), urine GAGs

🎯 DIAGNOSTIC TESTS

Leukocyte α-iduronidase, IDUA gene, skeletal survey (dysostosis multiplex)

✅ MOST ACCURATE TREATMENT

HSCT (best <2y, IQ>70), ERT (laronidase)

🧠 Mnemonic: “Hurler: Coarse face, Corneal clouding, HSCT early.”

🧪 Hunter (MPS II)

🩸 SCREENING

NBS: iduronate-2-sulfatase, urine GAGs

🎯 DIAGNOSTIC TESTS

Leukocyte iduronate sulfatase, IDS gene (X-linked), clear corneas

✅ MOST ACCURATE TREATMENT

ERT (idursulfase); HSCT less effective

🧠 Mnemonic: “Hunter: X-linked, clear corneas, no clouding, Hunter = He (male).”

🧪 Morquio (MPS IVA)

🩸 SCREENING

NBS: GALNS enzyme

🎯 DIAGNOSTIC TESTS

Keratan sulfate urine, GALNS gene, odontoid hypoplasia imaging

✅ MOST ACCURATE TREATMENT

ERT (elosulfase alfa), cervical fusion for instability

🧠 Mnemonic: “Morquio: Neck instability, Knock-knees, Short trunk.”

🧬 Lesch‑Nyhan (HPRT1)

🩸 SCREENING

Hyperuricemia, uric acid/creatinine ratio

🎯 DIAGNOSTIC TESTS

HPRT1 enzyme (lymphocytes/fibroblasts), HPRT1 gene, urate crystals

✅ MOST ACCURATE TREATMENT

Allopurinol (hyperuricemia), behavioral/physical restraints, no cure

🧠 Mnemonic: “Lesch-Nyhan: Self-biting, Dystonia, Hyperuricemia – Allopurinol, but behavior stays.”

🧬 APRT deficiency

🩸 SCREENING

2,8‑DHA stones (radiolucent, reddish-brown)

🎯 DIAGNOSTIC TESTS

Stone analysis (DHA), APRT enzyme, APRT gene

✅ MOST ACCURATE TREATMENT

Allopurinol, high fluid intake, low-purine diet

🧠 Mnemonic: “APRT: Allopurinol Prevents Recurrent (DHA) sTones.”

👴 Progeria (HGPS)

🩸 SCREENING

Clinical (alopecia, lipodystrophy, beaked nose, joint contractures)

🎯 DIAGNOSTIC TESTS

LMNA gene (c.1824C>T, p.G608G), progerin detection

✅ MOST ACCURATE TREATMENT

Lonafarnib (farnesyltransferase inhibitor), low-dose aspirin, cardiovascular management

🧠 Mnemonic: “Progeria: Premature aging, LMNA, Lonafarnib – ‘Lon’ for long life extension.”

🌞 AIP (PBGD def.)

🩸 SCREENING

Urine PBG (spot, elevated during attack)

🎯 DIAGNOSTIC TESTS

Urine PBG/ALA, HMBS gene, erythrocyte PBGD

✅ MOST ACCURATE TREATMENT

IV hemin, IV glucose (mild), givosiran for prevention, avoid barbiturates

🧠 Mnemonic: “AIP: Abdomen pain, dark Urine, PBG high, Hemin IV.”

🌞 PCT (UROD def.)

🩸 SCREENING

Plasma/urine porphyrins (uroporphyrin elevated)

🎯 DIAGNOSTIC TESTS

Urine porphyrin fractionation, UROD gene, HCV/HFE testing

✅ MOST ACCURATE TREATMENT

Phlebotomy or low-dose hydroxychloroquine, avoid alcohol/estrogen

🧠 Mnemonic: “PCT: Phlebotomy, Cutaneous blisters, Treat with Hydroxy.”

🌞 EPP (FECH def.)

🩸 SCREENING

Erythrocyte metal-free protoporphyrin

🎯 DIAGNOSTIC TESTS

Fractionated RBC protoporphyrin, FECH gene, liver biopsy if suspected hepatopathy

✅ MOST ACCURATE TREATMENT

Afamelanotide (Scenesse), physical sunscreens, avoid iron, liver transplant for hepatopathy

🧠 Mnemonic: “EPP: Extremely Painful Photosensitivity, Afamelanotide.”

🩸 Congenital Hyperinsulinism

🩸 SCREENING

Critical sample: low β-OHB, low FFA, positive glucagon response

🎯 DIAGNOSTIC TESTS

Insulin, C-peptide, ABCC8/KCNJ11 genes, 18F-DOPA PET for focal/diffuse

✅ MOST ACCURATE TREATMENT

Diazoxide (first-line); focal: surgical resection; diffuse: near-total pancreatectomy

🧠 Mnemonic: “HI: High insulin, Diazoxide, Focal surgery cures.”

🩸 Ketotic hypoglycemia

🩸 SCREENING

Hypoglycemia + ketosis, normal lactate/uric acid, normal GH/cortisol

🎯 DIAGNOSTIC TESTS

Diagnostic fast (ruling out other causes)

✅ MOST ACCURATE TREATMENT

Frequent feeds, cornstarch at bedtime (1-2 g/kg), avoid fasting

🧠 Mnemonic: “Ketotic kids: small, starved, cornstarch bedtime.”