STEPTRACKERBIOCHEMISTRY + GENETICS | INBORN ERRORS | RAPID-FIRE REVIEW

Enzyme Deficiency → Disease

The deficient enzyme, what builds up, and the disease that follows — one row each, with the page that explains it.

FOCUS ON
Think "substrate before the block builds up; product after the block runs short." Most are AR; X-linked ones to know: OTC, G6PD, HGPRT (Lesch-Nyhan), Fabry, Hunter, PDH (E1α), plus Menkes and adrenoleukodystrophy. Hypoglycemia and acidosis patterns are sorted on 11.04.
ENZYME
DISEASE
BUILDUP · KEY SIGN
PAGE
HGPRT
Lesch-Nyhan (XR)
Uric acid · self-mutilation, gout
1.03
Adenosine deaminase
SCID (AR)
dATP · no T or B function
1.03
UMP synthase
Orotic aciduria
Orotic acid · megaloblastic anemia, no hyperammonemia
1.03
Lysyl hydroxylase / oxidase (Cu)
Ehlers-Danlos / Menkes
Weak collagen cross-links
3.05
GlcNAc phosphotransferase
I-cell disease
Lysosomal enzymes in plasma · coarse face
2.04
Pyruvate kinase
PK deficiency
2,3-BPG ↑ · hemolytic anemia
8.01
Pyruvate dehydrogenase
PDH deficiency
Lactate, alanine · neuro deficits
8.02
G6PD
G6PD deficiency (XR)
Oxidant hemolysis · Heinz bodies, bite cells
8.05
NADPH oxidase
Chronic granulomatous disease
Catalase ⁺ infections · abnormal DHR
8.05
Aldolase B · fructokinase
Fructose intolerance · essential fructosuria
Fructose-1-P (toxic) · fructose (benign)
8.06
GALT · galactokinase
Galactosemia · galactokinase deficiency
Gal-1-P (toxic, E coli sepsis) · galactitol (cataracts)
8.06
Glucose-6-phosphatase
Von Gierke (GSD I)
Glycogen · hypoglycemia, lactic acidosis
8.07
Acid α-glucosidase · debranching · myophosphorylase
Pompe · Cori · McArdle
Cardiomegaly · limit dextrin · exercise cramps
8.07
OTC · CPS I · arginase
Urea cycle disorders
Ammonia (+ orotic acid in OTC) · arginine (arginase)
9.01
Phenylalanine hydroxylase · homogentisate oxidase · tyrosinase
PKU · alkaptonuria · albinism
Phe · homogentisate · no melanin
9.03
Cystathionine β-synthase · BCKDH
Homocystinuria · MSUD
Homocysteine · Leu, Ile, Val
9.04
PBG deaminase · UROD · ALA dehydratase/ferrochelatase
AIP · PCT · lead poisoning
PBG, ALA · uroporphyrin · ALA, protoporphyrin
9.05
MCAD · carnitine transporter
MCAD deficiency · primary carnitine deficiency
C8–C10 acylcarnitines · hypoketotic hypoglycemia
10.01
LPL / ApoC-II · LDL receptor · ApoE2
Dyslipidemia types I · IIa · III
Chylomicrons · LDL · remnants
10.04
Hex A · sphingomyelinase · glucocerebrosidase · α-Gal A
Tay-Sachs · Niemann-Pick · Gaucher · Fabry
GM2 · sphingomyelin · glucocerebroside · Gb3
10.05
α-L-iduronidase · iduronate sulfatase
Hurler · Hunter
Heparan + dermatan sulfate
10.05

X-linked enzyme deficiencies

ENZYME
DISEASE
CLUE
OTC
Urea cycle defect
Ammonia + orotic acid
G6PD
Hemolysis
Fava, sulfa, primaquine
HGPRT
Lesch-Nyhan
Self-mutilation
α-Galactosidase A
Fabry
Burning feet, angiokeratoma
Iduronate sulfatase
Hunter
No corneal clouding
PDH E1α
PDH deficiency
Lactic acidosis

Benign vs dangerous partners

BENIGN
DANGEROUS
WHY
Essential fructosuria
Hereditary fructose intolerance
Phosphate trapped as F-1-P
Galactokinase ↓
Classic galactosemia
Gal-1-P toxic
Alkaptonuria (early)
Tyrosinemia I
Liver/kidney toxins

How it's tested

COMMON CONFUSIONWhen two enzymes sit in a row, the first (kinase) defect is usually milder because the unphosphorylated sugar can leave in urine.
THE TRAPQuestions describe the buildup and ask for the enzyme — work backward from the substance that accumulates.
YOUR APPROACHIdentify what's elevated → the enzyme just after it → inheritance → treatment (restrict substrate, supply product, cofactor).

If you see… think…

↑ Uric acid + self-injury → HGPRT
↑ Orotic acid, normal ammonia → UMP synthase
↑ Orotic acid + ↑ ammonia → OTC
↑ C8 acylcarnitines → MCAD
↑ PBG in urine → PBG deaminase (AIP)
↑ Homogentisate → homogentisate oxidase (alkaptonuria)
↑ Branched-chain amino acids → BCKDH (MSUD)
↑ Glucocerebroside in macrophages → glucocerebrosidase (Gaucher)
↑ GM2 ganglioside → hexosaminidase A
↑ Chylomicrons in fasting plasma → LPL or ApoC-II