Index of Diseases
Disease |
Primary Clinical Manifestation |
Cause |
scurvy |
sores that do not heal |
lack of vitamin C for conversion of proline to hydroxyproline in colligen |
lathyrism |
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 |
Type VIII GSD |
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) |
Acatalasemia |
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 |
hypertension |
no sex hormones/cortisol from cholesterol |
21-alpha hydroxylase deficiency |
masculinization |
diminished glucocorticoid/mineralcorticoid from cholesterol |
11-beta hydroxylase deficiency |
masculinization, hypertension |
low cortisol, corticosterone, aldosterone; high deoxycorticosterone synthesis |
lead poisoning |
anemia |
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 |
sorbitolemia |
serious eye problems |
high blood sugar leading to sorbitol buildup (aldose reductase faster than sorbitol dehydrogenase) |
galactosuria |
slow galactose metab, cataracts, gal in urine |
deficient galactokinase--buildup dulcitol (no degradation) |
galactosemia |
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) |
hypermethioninemia |
severe liver disease |
methionine adenosyltransferase deficiency |
cystathioninuria |
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 |
alkaptonuria |
elevated homogentisate, dark urine, benign |
homogentisate oxidase deficiency--inability to break down homogentisic acid |
goiter |
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 |
Albinism |
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 |