Index of Diseases



Primary Clinical Manifestation



sores that do not heal

lack of vitamin C for conversion of proline to hydroxyproline in colligen


abnormal keratin (no crosslink)

beta-aminopropionylnitrile (in sweet peas, lythyrus odoratus) interferes with lysyl hydroxylase

anti-trypsin deficiency

severe emphasema

trypsin not secreted from ER (lack of conformational maturation)

familial hypercholesterolemia

pathologically high serum cholesterol

LDL receptors not secreted from ER (lack of conformational maturation)

alpha thalassemia

stillborn from hypoxia

insufficient synthesis of alpha hemoglobin chain (chromosome 16)--primarily Asian incidence

beta thalassemia

anemia, dependent upon transfusion

insufficient beta hemoglobin (chromosome 11)--use gamma until late childhood, freq. iron poison

sickle cell anemia

various--painful crisis/splenomegaly/ulcerations

RBC sickle at low pO2 because of glu to val mutation at position 6 (hydrophobic interaction)

I-cell disease

inclusions within lysosomes--fatal

mannose-6-phosphate not added to N-glycan lysosomal digestive enzymes in Golgi (no sorting)

glycolysis-associated anemia

severe anemia

phosphoglycerate kinase or pyruvate kinase deficiency

Type Ia GSD--von Gierke

hypoglycemia, SIDS, hepatomegaly

glucose-6-phosphetase deficiency

Type Ib GSD--von Gierke

hypoglycemia, SIDS, hepatomegaly

glucose-6-phosphate transporter deficiency

Type Ic GSD--von Gierke

hypoglycemia, SIDS, hepatomegaly

ER inorganic phosphate transporter deficiency

Type Id GSD--von Gierke

hypoglycemia, SIDS, hepatomegaly

glut-7 transport deficiency (glucose out of liver ER)

Type II GSD--Pompe

excessive glyc, infant cardiac death

alpha-1,4-glucosidase deficiency (lysosomal glycogen degradation pathway)

Type III GSD--Cori

hypoglycemia, hepatomegaly

no debranching enzyme (much glycogen in short branches)

Type IV GSD--Andersen

liver cirrhosis, death by age 2

no branching enzyme (very long branches)

Type V GSD--McArdle

exercise:exhausted, no lactate, cramps

no skeletal muscle phosphorylase activity--unable to mobilize glycogen during exercise

Type VI GSD--Hers

hypoglycemia, hepatomegaly

no liver phosphorylase activity--elevated hepatic glycogen

Type VII GSD--Tarui

exercise:exhausted, no lactate, cramps

muscle phosphofructokinase deficiency--unable to mobilize muscle glycogen


hypoglycemia, mild hepatomegaly

no liver phosphorylase kinase--elevated hepatic glycogen (X-linked--all other GSD autosom.rec.)

Methylmalonyl aciduria

failure to grow, mental retardation

no methylmalonyl CoA mutase (propionyl CoA metabolism)

Refsum's Disease

various neurological problems

buildup of phytanic acid (from chlorophyll) due to alpha-beta oxidation or monooxygenase defic.

Zellweger's Syndrome

infant death, severe neuro problems

no peroxisome matrix enzymes (peroxisome "ghosts") no plasmalogen synthesis (myelin)

Neonatal Adrenolenkodystrophy

mild to severe neurological problems

some peroxisome matrix enzymes missing (catalase present)

Infantile Refsum's Disease

various neurological problems

buildup of phytanic acid (from chlorophyll) due to missing peroxisomal enzymes

Hyperpiperolic Acidemia

various neurological problems

inability to metabolize hyperpiperolic acid due to missing peroxisomal enzymes

Rhizomelic chondrodysplasia punctata

various neurological problems

structurally abnormal peroxisomes (although abundant)


oral gangrene and ulcerations

single protein missing from peroxisomes

3-beta hydroxysteroid dehydrogenase defic

high urinary salt excretion, early death

no androgen/estrogen/glucocorticoid synth from cholesterol

17-alpha hydroxylase deficiency


no sex hormones/cortisol from cholesterol

21-alpha hydroxylase deficiency


diminished glucocorticoid/mineralcorticoid from cholesterol

11-beta hydroxylase deficiency

masculinization, hypertension

low cortisol, corticosterone, aldosterone; high deoxycorticosterone synthesis

lead poisoning


lead inhibition of aminolevulinic acid (AVA) dehydratase and ferrochelatase

acute intermittant porphyria

neurological/psychiatric problems

uroporphyrinogen I synthetase deficiency

congenital erythro-poietic porphyria

photosens, hemolyt.anemia, skin lesions, sphlenomegaly

uroporphyrinogen III cosynthetase deficiency

porphyria cutanea tarda

cutaneous photosensitivity, skin lesions

uroporphyrinogen decarboxylase deficiency

hereditary coproporphyria

cutaneous photosensitivity, skin lesions

coproporphyrinogen oxidase deficiency

Glucose-6-phosphate dehydrog. defic.

hemolytic anemia

inability to maintain reduced glutathione (low RBC [NADPH])--incidence: 100M (most common)

Thiamin deficiency

various, including neurological, pneumonia

buildup of ribose-5-phosphate in RBC, low NADPH

Wernicke-Korsakov Syndrome

eye paralysis, mental derange, abnorm.gait

no transketolase activity due to failure of thiamin to bind (common in alcoholics)

Benign Fructosuria

impaired fructose metabolism, normal

deficient fructokinase

Hereditary Fructose Intolerance

nausea/abd pain, hypoglyc, reduced renal fn.

deficient fructose-1-phosphate aldolase


serious eye problems

high blood sugar leading to sorbitol buildup (aldose reductase faster than sorbitol dehydrogenase)


slow galactose metab, cataracts, gal in urine

deficient galactokinase--buildup dulcitol (no degradation)


cataracts, vomiting, hypoglycemia

deficient Gal-1-P/Glu-1-P UMP transferase--accumulate dulcitol and gal-1-P in RBC

hereditary lactose intolerance

inability to digest milk

deficient lactase

oxoprolinemia (oxoprolinuria)

buildup of 5-oxoproline

glutathione synthase deficiency (gamma-glutamyl cyclotransferase cuts gamma-glutamylcysteine)

Gauchet's disease

ment.retard., marrow/lung/kidney, hepatosphlenomegaly

no beta-glucocerebrosidase so buildup of glucocerebrosides

GM1 gangliosidosis

ment.retard., hapatomegaly, skeletal deformity, fatal

no beta-galactosidase, so buildup of GM1 gangliosides and gal-oligosaccharides

Tay-Sachs Disease

ment.retard., seizures, blindness, musc. weakness, fatal

no beta-hexosaminidase A, so buildup of GM2 gangliosides

Sandhoff's Disease

ment.retard./seisures/blindness--rapid progression, fatal

no beta-hexosaminidase, so buildup of globosides

Farby's Disease

kidney/cardiac failure, lower extremity pain, skin rash

alpha-galactosidase deficiency so buildup of globosides

Metachromatic Leukodystrophy

ment.retard., demyelination, paralysis/dementia

sulfatide sulfatase deficiency so buildup of sulfatides

Krabbe's Disease

ment.retard., paralysis/convulsions, blind/deaf/fatal

no beta-galactosidase, so buildup galactocerebrosides

Farber's Disease

painful/deformed joints, subcutaneous nodules, fatal

ceramidase deficiency, so buildup of ceramides

Niemann-Pick Disease

ment.retard., hepatosphlenomegaly, fatal

sphingomyelinase deficiency so buildup of sphingomyelins

Hurler's Syndrome

ment.retard., dwarfism/skel defects, corneal/heart probs

alpha-L-iduronidase deficiency in lysosomes (M6P signalling)

Hunter's Syndrome

ment.retard., dwarfism/skel defects, heart probs

iduronidate sulfatase deficiency in lysosomes (M6P signalling)

Sanfilippo's Syndrome Type I

severe mental retardation

heparan sulfamidase deficiency in lysosomes (M6P signalling)

Sanfilippo's Syndrome Type II

severe mental retardation

N-acetylglucosaminidase deficiency in lysosomes (M6P signal)

Sanfilippo's Syndrome Type III

severe mental retardation

N-acetyltransferase deficiency in lysosomes (M6P signalling)

Sanfilippo's Syndrome Type IV

severe mental retardation

N-acetylglucosamine-6-sulfatase deficiency in lysosomes (M6P)

Scheie's Syndrome

stiff joints/claw hands, corneal clouding, arotic regurgitation

no alpha-L-idulonidase in lysosomes (M6P signalling)

Sly's Syndrome

physical deformity, hepatosphlenomegaly

beta-glucuronidase deficiency in lysosomes (M6P signalling)

PDC deficiency

shallow breath, ketotic acidosis, high lactate

no PDC function--convert glucose to lactate and produce ketone bodies

MCAD (medium chain acid deficiency)

flulike, non-ketotic hypoglyc, FA in blood/urine

no medium chain fatty acid breakdown--excreted as carnitine ester

urea cycle defects (each enzyme)

all have hyperammonemia

deficiency in one of the enzymes of the urea cycle

folate deficiency

CNS problems, anemia

no folate absorbtion/reduction/transferase activity--FI-glu in urine after hist load

pernicious anemia (megaloblastic anem.)

anemia with hypersegm lymphocyt, large RBC

no intrinsic factor or dietary B12--FI-glu in urine

adenosyl B12 transferase deficiency

acidosis, methylmalonic acid in urine

inability to produce adenosyl B12 for propionic acid metabolism (odd chain fatty acids)

methylmalonyl CoA mutase deficiency

acidosis, methylmalonic acid in urine

inability to metabolize propionic acid (odd chain fatty acids)

homocysteinemia (-uria)

ocular (lens)/skeletal/CNS/vascular problems

cystothione-beta-synthase deficiency (treat with betaine)


severe liver disease

methionine adenosyltransferase deficiency


liver/CNS/thyroid/renal problems, B12 defic

no gamma-cystathionase

orotic aciduria

megaloblastic anemia, mental retardation,lethal

orotate phosphoribosyltransferase/carboxylase (UMP synthase complex) defic. (treat with uridine)

Lesch-Nyham Syndrome

neuro problems, aggressive, self-destructive

HGPRT deficiency (associated with gout and high purine levels)

gout (hyperuricemia)

arthritic joint problems, intermittant attacks

many causes--high uric acid (sometimes associated with kidney stones) (treat with allopurinol)

Type I hyperphenlalanemia (classical PKU)

mental retardation

no phenylalanine hydroxylase

Type II hyperphenylalanemia

normal--high phenylalanine in blood

low phenylalanine hydroxylase

Type III hyperphenylalanemia

normal--high phenylalanine in blood

delayed maturation of phenylalanine hydroxylase

Type IV hyperphenylalanemia

brain dysfunction

dihydropterine reductase deficiency (no dietary component)

Type V hyperphenylalanemia

brain dysfunction

defect in dihydrobiopterine synthesis (from GTP)

Tyrosinosis (Medes')

parahydroxyphenylpyruvate (p-HPP) in urine

p-HPP oxidase deficiency

Transitional Neonatal Tyrosinemia

high tyrosine levels, usually premature

early tyrosine oxidation enzymes not developed

Persistant Hypertyrosinemia

mental retardation, ocular/skin problems

cytosolic tyrosine aminotransferase deficiency


elevated homogentisate, dark urine, benign

homogentisate oxidase deficiency--inability to break down homogentisic acid


enlarged thyroid

insufficient iodine for thyroid hormone maturation (thyroglobulin)

propionic acidemia

mental retardation, hyperammonemia

propionic CoA carboxylase deficiency

Maple Syrup Urine Disease

CNS problems, mental retardation, fatal

branch chain alpha-ketoacid dehydrogenase deficiency--unable to metabolize BCAA


no skin pigment, increased skin cancer risk

tyrosinase deficiency--no synthesis of melanin from tyrosine

Adenosine deaminase deficiency

severe combined immunodeficiency, death by 2

ADA deficiency--no purine degradation, so accumulation of dATP inhibits ribonuc.reductase