Enzyme Deficiencies of Glycolysis and TCA

DISEASE NAME DEFICIENCY SIGNS/SYMPTOMS

MYOD2 Glucokinase Similar to diabetes
HK I Deficiency Hexokinase Hemolytic anemia characterized by
severe/chronic hemolysis
PK Deficiency Liver Isoform Pyruvate Kinase, liver Jaundice, large spleen, mild or
severe hemolysis
PK Deficiency RBC Isoform Pyruvate Kinase, RBC Hemolytic anemia
PDH Deficiency Pyruvate Dehydrogenase Associated with abnormal
mitochondria function;
developmental delay, intermittent
ataxia, hypotonia, abnormal eye
movements, and seizures

Glycogen Storage Diseases

DISEASE NAME DEFICIENCY SIGNS/SYMPTOMS
GSD 0 Glycogen Synthase Hypoglycemia, failure to thrive,
hyperketonemia, and early death
GSD 1a/Von Gierkes Glycogen-6-Phosphotase Doll like face, hyperlipidemia,
hypoglycemia, elevated lactate,
hypotonia, hepatomegaly,
respiratory infections, growth
retardation
GSD V/McArdles Glycogen Phosphorylase, SKM Exercise intolerance, red urine,
fatigue muscle cramps, pain,
stiffness, and weakness
GSD VI/Hers Glycogen Phosphorylase, liver Hypoglycemia, hepatomegaly,
elevated lactic acid
GSD VII/Tarui Phosphofructokinase-1, SKM Myoglobinuria, anemia, increased
muscle glycogen content, nausea
and vomiting, muscle weakness and
cramps, myotonia, hyperuricemia
GSD 15 Glycogenin-1, muscle form Muscle weakness, glycogen
depletion in skeletal muscle and
heart, cardiac arrhythmia, twitching
Gluconeogenesis and PPP Disorders
DISEASE NAME DEFICIENCY
PC Deficiency Pyruvate Carboxylase
PEPCK Deficiency Phosphoenolpyruvate carboxykinase
G6PDH Deficiency Glucose-6-Phosphate
Dehydrogenase/lack of NADPH in
RBC/ GSH defense system
Fructose, Lactose, and Galactose
Metabolism Disorders
DISEASE NAME DEFICIENCY
Essential Fructosuria Fructokinase
Fructose Intolerance Aldolase B
Lactose Intolerance Lactase; congenital in
premature infants; secondary acids are produced; more
to the surgical removal of
small intestine; mucosal cell diarrhea
damage
Classic Galactosemia Galactose-1-P
uridylyltransferase
Galactokinase Deficiency Galactokinase
SIGNS/SYMPTOMS
Lactic acid accumulation in
blood; disruption in
gluconeogenesis
Acute episodes of severe
lactic acidosis associated with
hypoglycemia;
gluconeogenesis inhibited
from lactate, pyruvate, and
alanine
Hemolytic anemia
SIGNS/SYMPTOMS
Easily eliminated in urine
F1P accumulation inhibits
gluconeogenesis and
Glycogenolysis; hypoglycemia
and lactic acidosis
Gas and short-chained fatty
water in colon; pain and
Accumulation of galactose-1-
P; infants develop feeding
difficulties, diarrhea,
vomiting, failure to thrive,
liver damage, developmental
delay, and intellectual
disability
aldolase reductase converts
galactose to galactitol;
cataracts
Fatty Acid Oxidation Diseases
DISEASE NAME
MCAD deficiency
MCM deficiency
Connective Tissue Diseases
DISEASE NAME
Marfan Syndrome
Osteogenesis Imperfecta
Epidermolysis bullosa
simplex (EBS)
Junctional epidermolysis
bullosa (JEB)
Dystrophic epidermolysis
bullosa (DEB)
EDS types I and II (“classic”)
EDS type III (“hypermobility”)
EDS type IV (“vascular”)
DEFICIENCY
Medium Chain Acyl CoA
Dehydrogenase
Methylmalonyl CoA Mutase
DEFICIENCY
Mutations in gene for
fibrillin-1
Dominant mutation in
gene for type I collagen
Defects in genes for
Keratins 5 and 14 and
plectin
Mutations in genes for
laminin-332, plectin, and
a6b4 integrin
Defects in type VII
collagen
Deficits in type V collagen
Deficits in glycoprotein
tenascin-X
Deficits in type III collagen
SIGNS/SYMPTOMS
Hypoglycemia during fasting
and lethargy; can’t break
down medium chain fatty
acids
Methylmalonic acid builds up
and damages the nervous
system and other organs;
fatigue, vomiting,
dehydration, hepatomegaly,
kidney disease, pancreatitis
SIGNS/SYMPTOMS
Tall and thin; scoliosis, dental
problems, abnormalities in the
lens of the eye, enlargement of
proximal aorta
Fragile bones, low muscle mass,
loose joints and ligaments; gray
sclera, thin skin, decreased
growth, fragile teeth,
respiratory dysfunction
Blistering in epidermis
Blistering in basal membrane
between the epidermis and
dermis
Blisters occur within the dermis
?
Reduced density of collagen
fibers and disruption of elastic
fibers
Impacts the structure of blood
vessels
EDS type VI
(“kyphoscoliosis”)
EDS types VIIA and VIIB
(“arthrochalasia”)
Scurvy
Deficits in LH enzyme that ?
hydroxylates specific
lysine residues
Deficits in structure of ?
type I collagen
Vitamin C Can’t hydroxylate proline/lysine
for collagen synthesis

Lipoprotein Diseases
DISEASE NAME DEFICIENCY/PROBLEM
Type I hyperchylomicronemia 1a: lipoprotein lipase
1b: ApoC-II
1c: mutation in lipoprotein
lipase the inhibits activity
Type II Overproduction of HDL from
hyperalphalipoproteinemia overproduction of apoA
Type II Overproduction of LDL;
hyperbetalipoproteinemia increase of TGs and FAs
Type IIA Defects in LDL receptors;
hypercholesterolemia increased LDL
Type III Defect in apoE; elevated
dysbetalipoproteinemia or levels of chylomicrons and
remnant removal disease VLDL
Type IV Overproduction of VLDL and
hypertriglycerideemia elevated cholesterol levels
Apolipoprotein B deficiency Missense mutation in apoB;
high LDL and increased half
life
CETP deficiency Absent cholesterol ester
transfer protein; elevated
HDL
Abetalipoproteinemia Defects in apoB containing
lipoproteins (chylomicrons
and VLDL); defective
microsomal triglyceride
transfer protein; absence of
SIGNS/SYMPTOMS
High chylomicrons and TGs;
pancreatitis, lipemia retinalis,
and cutaneous eruptive
xanthomas; treat with low fat
diet
May have cardio-protective
benefits
Cardiovascular and cornary
artery disease
Hypercholesterolemia,
atherosclerosis and cornary
artery disease
Tuberous and palmar
xanthomas,
hypercholesterolemia, and
atherosclerosis
Associated with glucose
intolerance and
hyperinsulinemia; associated
with type II diabetes, obesity,
and alcoholism
Atherogenesis and cornary
artery disease
Not associated with cornary
artery disease
Malabsorption of fat and fat
soluble vitamins; failure to
thrive, diarrhea, abnormal
star-shaped erythrocytes,
and fatty stools; retinal
 chylomicrons; vitamin E
deficiency
LCAT deficiency/Fish eye Absence of LCAT; free
disease cholesterol can’t convert to
cholesterol ester
Hypobetalipoproteinemia Mutational defects in apoB;
low LDL but VLDL and HDL
are normal; can cause
stabilization of LDL;
Hypoalphalipoproteinemia Low HDL from failure to
synthesize functional apoA
Tangier disease (HDL Low HDL but prebeta-HDL
deficiency) can be detected; defective
ABCA1 transporter
Other Diseases
DISEASE NAME DEFICIENCY
Niemenn-Pick Lysosomal enzyme that
breaks down excess
sphingomyelin
Scott’s syndrome Blood platelet scramblase
Progeria Mutation in genes that code Premature aging; increased
the nuclear lamins
Wolman disease Lysosomal acid lipase (a
lysosomal enzyme required
for metabolism of cholesterol demonstrate failure to thrive
esters and TGs in the liver
from LDL); cholesterol ester
and TGs build up
degeneration and impaired
neurological function
develop later
Reverse cholesterol transport
is inhibited (HDL); cholesterol
crystals accumulate in cornea
of eye; proteinurea and
kidney failure
Development of fatty liver
Increased cardiovascular
disease
Accumulation of yellow
orange lipid deposits in the
tonsil and hypertrophy of
tonsils; elevated
triglycerides, develop
neuropathy, premature
atherosclerosis, enlarged
spleen and liver, clouding of
cornea, early onset
cardiovascular disease
SIGNS/SYMPTOMS
Hepatosplenomegaly,
abdominal distension, ataxia,
dystonia, etc.
Reduced ability of platelets
to promote blood
coagulation
rate of cell death
Accumulated fat causes
malabsorption; infants
and liver failure.
Vitamins and Trace Elements
VITAMIN FUNCTION
Vitamin A Component of visual pigment;
maintenance of epithelia;
maintenance of resistance to
infection
Vitamin D Facilitates intestinal absorption of
calcium and phosphorous and
mineralization of bone (when
deficient PTH increases)
Vitamin E Antioxidant; scavenges free
radicals
Vitamin K Cofactor in hepatic carboxylation
of procoagulants (factor II, VII, IX,
X; and protein C and S)
Vitamin B1 Coenzyme in decarboxylation
(Thiamine) reactions
DEFICIENCY
Night blindness, xerophthalmia,
blindness, bitot spots, corneal
ulcer, Keratomalacia;
squamous metaplasia;
vulnerable to infection
Hypocalcemia; increased
calcium absorption,
mobilization of calcium from
bone, decreased calcium
excretion, and increased
phosphorous excretion; Rickets
in children (bowed legs, knock-
knees, frontal “bossing”,
rachitic rosary, pigeon breast
deformity, Harrison groove,
lumbar lordosis, craniotubes,
excess osteoid microscopically);
osteomalacia in adults
(weakened bones and poor
remodeling, excess osteoid
microscopically)
Spinocerebellar degeneration
(ataxia, muscle weakness,
impaired vision); decreased
RBC survival (hemolysis)
Bleeding diathesis
(hematomas, hematuria,
melena, bleeding gums);
hemorrhagic disease of the
newborn
Dry beriberi (peripheral
nerves/polyneuropathy); wet
beriberi (high CO heart failure,
dilated cardiomyopathy);
Wernicke (impaired sensory
perception)-Korsakoff
(dementia, amnesia,
confabulation) syndrome
 (shrunken and hemorrhagic
mammillary bodies)
Vitamin B2 Converted to flavin coenzymes and Cheilosis, stomatitis, glossitis,
(Riboflavin) used in intermediary metabolism; dermatitis, corneal
antioxidant; converts B6 and Folate vascularization (keratosis),
into useable forms; RBC production erythroid hypoplasia
Vitamin B3 (Niacin) Incorporated into NAD and NADP; Pellagra (dementia, dermatitis,
involved in oxidation-reduction diarrhea)
reactions
Vitamin B5 Incorporated into coenzyme A; Acne and paresthesia
(pantothenic acid) involved in oxidation of FAs and (tingly/prickly)
carbs
Vitamin B6 Derivatives serve as coenzymes in Cheilosis, glossitis, dermatitis,
(pyridoxine) many intermediary reactions; peripheral neuropathy,
production of serotonin and convulsions
norepinephrine; formation of
myelin
Vitamin B7 (Biotin) Cofactor in carboxylation reactions Brittle nails, hair loss, skin rash;
infants have impaired growth
and neuro D/OS
Vitamin B9 (folate) Essential for transfer and use of Megaloblastic anemia, neural
one-carbon units in DNA synthesis tube defects (spina bifida and
anencephaly), colon cancer
Vitamin B12 Required for normal folate Combined system disease
(Cobalamin) metabolism and DNA synthesis; (megaloblastic anemia and
Maintenance of myelinization of degeneration of posterolateral
spinal cord tracts; cofactor is spinal cord tracts); Vegans are
methionine synthesis; absorption at higher risk for primary
requires IF and R binder
Vitamin C (ascorbic Serves in many redox reactions and Scurvy (hemorrhage and
acid) hydroxylation of collagen; healing defects, bone disease in
antioxidant children); hyperkeratotic rash,
dry and splitting hair, anemia;
precautions: can have a diuretic
effect, increase iron absorption
Zinc Component of enzymes, principally Acrodermatitis Enteropathica
oxidases (AR form of deficiency,
dermatitis around mouth and
limbs, alopecia, diarrhea);
happens with TPN
Iron Essential component of Hypochromic, microcytic
hemoglobin as well as several iron- anemia (small and pale);
containing metalloenzymes; meat fatigue, brittle nails,
 is heme iron and dark greens are
non-heme iron
Iodine Component of thyroid hormone
Copper Component of cytochrome c
oxidase, lysyl oxidase
Fluoride Replaces calcium during
remineralization of teeth,
producing fluorapatite, which is
more resistant to acids
Selenium Component of GSH peroxidase;
anti-oxidant with vitamin E;
contribute to proper production of
thyroid hormone
Manganese Required for healthy bones
Molybdenum Coenzyme of oxidase enzymes
Chromium Potentiates insulin activity
inflamed/sore tongue,
weakness, paresthesia, and
more; hemochromatosis is
caused by too much iron
(primary: Ar; secondary: due to
transfusions; tissue damage
and bronze discoloration;
treated with phlebotomy)
Goiter and hypothyroidism
Muscle weakness, neurologic
defects, Menkes (abnormal
collagen crosslinking, X linked,
progressive degenerative
neurologic disorder, cells cant
transport copper), Wilson’s is
an overdose (AR, impaired
excretion of copper into bile,
kayser-fleischer rings)
Dental caries; toxicity is
fluorosis
Myopathy, cardiomyopathy
(Keshan disease); hypothyroid
and fatigue; kashin-beck
disease (cartilage degeneration
and necrosis)
Dermatitis,
hypocholesterolemia; toxicity
causes neurologic symptoms
Seizures (genetic sulfite oxidase
deficiency); toxicity causes
gout-like symptoms; happens
with TPN
Happens with long term TPN;
glucose intolerance, weight
loss, ataxia, peripheral
neuropathy