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0- Glycogen synthase in the liver

Low glycogen storage in liver. Fas@ng
hypoglycemia, hyperclygemia a[er feeding.

I- Von Gerke
AR. Severe fas@ng hypoglycemia, glycogen in
liver. blood lactate. Hepatomegaly.


Galactokinase deciency

Essen-al fructosuria

Fructose Intolerance
Aldolase B

AR. Benign. (fructose

is not trapped in
cells). Fructose is
found in blood and

AR. Hypoclygemia, jaundice, cirrhosis, vomi@ng

Fructose-1-P Phosphates inhibi@on of
glycogenolysis and gluconeogensis. Symptoms
follow consump@on of fruit, juice, honey.
Reducing sugar in urine, dips@ck -.
Tx: Fructose and sucrose (glu + fru)

AR. Mild. Galac@tol

accumulates. Galactose
appears in blood and urine,
infan@le cataracts. May
ini@ally present as failure to
track objects or to develop a
social smile.

II- Pompe
Lysosomal -1,4-glucosidase (acid maltase)
AR. Cardiomegaly, early death. glycogen in
vacuoles of lysosomes. Normal blood sugar
and glycogen structure.


Classic Galactosemia
Galactose-1-phosphate uridyltransferase


AR. Damage is caused by accumula@on of toxic

substances (including galac@tol, which accumulates
in the lens of the eye).
Symptoms: failure to thrive, jaundice,
hepatomegaly, infan@le cataracts, intellectual
disability. Treatment: exclude galactose and
lactose (galactose + glucose) from diet.
Serious defects lead to PO43 deple@on. Can lead to
E. coli sepsis in neonates.

Liver disease, urea cycle enzyme

NH4+ which ketoglutarate
Tx: protein diet. Benzoate,
phenylbutyrate which bind amino acid
& excre@on. Lactulose acidies the
GI tract to trap NH4 to excre@on.

N-acetylglutamate Deciency
Presenta@on is iden@cal to
carbamoyl phosphate synthetase I
deciency. However,ornithine
with normal urea cycle enzymes
suggests hereditary N-
acetylglutamate deciency.

Ornithine Transcarbamylase
XLR. (other urea enxymes deciencies are AR).
Interferes with the bodys ability to eliminate
ammonia. O[en evident in the rst few days of life,
but may present with late onset. Excess carbamoyl
phosphate is converted to oro@c acid (part of the
pyrimidine synthesis pathway).
Findings:oro@c acid in blood and urine,BUN,
symptoms of hyperammonemia. No megaloblas@c
anemia (vs. oro@c aciduria).
Phenylalanine Hydroxylase
Tetrahydrobioterin (Malignant PKU)
intellectual disability, growth retarda@on, seizures,
fair skin, eczema, musty body odor.

Debranching, -1,6-glucosidase
AR. Milder type I with normal lactate,
gluconeogenesis intact. Glycogen with short

Alkaptonuria (ochronosis)
Homogentsate oxidase
AR. Benign. Findings: dark connec@ve @ssue, brown
pigmented sclerae, urine turns black on prolonged
exposure to air. May have debilita@ng arthralgias
(homogen@sic acid toxic to car@lage).

IV- Andersens
Branching, 4,6 transferase
Long, unbranched glycogen. Cirrhosis, early

Cystathionine Synthase
(Tx: methionine, cys@ene, B12, folate)
Cystathionine synthase anity for PLP (Tc: B6
& cysteine)
Homocysteine Methyltransferase/Methionine
(Tx: methionine)
homocysteine in urine, intellectual
disability, osteoporosis, tall stature, kyphosis, lens
subluxa@on (downward and inward), thrombosis,
and atherosclerosis (stroke and MI).

V- McArdle
Skeletal muscle glycogen phosphorylase
AR. normal glycogen in muscle, but cannot
break it down, leading to painful muscle
cramps, myoglobinuria (red urine) with
strenuous exercise, and arrhythmia from
electrolyte abnormali@es.
VI- Hers
HepaDc Glycogen phosphorylase
VII- PFK-1 Deciency
Hemoly@c anemia, hemoglobinuria,

AR, common. Hereditary defect of renal PCT and
intes@nal amino acid transporter for Cysteine,
Ornithine, Lysine, and Arginine Excess cys@ne in the
urine can lead to precipita@on of hexagonal cys@ne
Urinary cyanide-nitroprusside test is diagnos@c.
Tx: urinary alkaliniza@on (e.g.,
potassium citrate, acetazolamide) and chela@ng
agentssolubility of cys@ne stones; good hydra@on.
Cys@ne is made of 2 cysteines connected by a
disulde bond.

FaNy Acids
Carni-ne deciency
inability to transport LCFAs into the
mitochondria, resul@ng in toxic accumula@on.
Causes weakness, hypotonia, and hypoketo@c
Acyl-CoA Dehydrogenase Deciency

Maple Syrup Urine Disease

-ketoacid dehydrogenase (B1)
AR. Blocked degrada@on of branched amino acids
(leucine, isoleucine, valine) -ketoacids in blood.
Tx: restrict BCAA, supplement thiamine.

dicarboxylic acids, glucose & ketones.

Acetyl CoA is allosteric ac@vator of PC in
gluconeogenesis. Acetyl-Coa- fas@ng
hypoglycemia, SIDS. Avoid fas@ng.

Def: Night blindness, xerosis cu@s, alopecia, corneal
degenera@on, immune suppression. Common in
Asia, Africa, SA.
Tox: Arthralgia, scaly skin, alopecia, cerebral
edema, osteoporosis, hepa@c dysfunc@on.
Teratogen (cle[ palate, cardiac)
Vit A may be used to treat measels, pneumonia,

Def: Wernicke-Korsako, beriberi (dry- poly neuri@s,
symmetric muscle was@ng. Wet- high output cardiac failure/
dilated cardiomyopathy, edema). transketolase ac@vity
following B1 administra@on

B2/Riboavin (FAD & FMN)

Def: Cheilosis, corneal vasculariza@on

B3/Niacin (NAD, NADP; from Tryptophan)

Def: Glossi@s. Pellegra- Diarrhea, Demen@a, Derma@@s
(may be caused by Hartnup disease-Tryp absorp@on,
Malignant carcinoid syndrome- tryp metabolism,
isoniazid- B6; B2 & B6 req. for synthesis).
Tox: Facial ushing (induced by PGs, not histamine),
hyperglycemia, hyperuricemia.

B5/Pantothenate (CoA)
Def: Derma@@s, enteri@s,
alopecia, adrenal insuciency

B6/Pyridoxine (PLP)
Deciency may be induced by isoniazid and
oral contracep@ves.
Def: Convulsions, hyperirritability, peripheral
neuropathy, sideroblas@c anemia due to
impaired heme synthesis and iron excess

MC. Deciency can be induced by drugs
(phenytoin, sulfonamides, methotrexate), jejunal
resec@on, leafy green intake.
Def: Macrocy@c, megaloblas@c anemia,
hypersegmented PMN. Glossi@s. Homocysteine,
normal methylmalonic acid.

Large reserve pool (years) in liver). Deciency caused by
insucient intake (vegetarian), malabsorp@on (sprue, enteri@s,
Diphyllobothrium latum, IF/Pern anemia/gastric bypass,
absence of terminal ileum/Crohns. Def: Macrocy@c, megalo
anemia, hyperseg PMNs, paresthesias & subacute combined
degenera@on (DCs, lateral CST, spinocerebellar tracts; due to

Def: Scurvy- swollen gums, bruising,
hemarthrosis, anemia, poor wound
healing, perifollicular and
subperiosteal hemorrahes,
corkscrew hair. immune
response. . hydroxyla@on of proline

D [[25-OH D3 = storage form]

D2 = Ergocalciferol; plants
D3 cholecalciferol; milk, stratum basale
Def: Rickets, osteomalacia, hypocalcemia, tetany.
Breasqed infants need oral vitamin D
Excess in sarcoidosis (due to ac@va@on by macros).
Hypercalcemia, hypercaliuria, loss of appe@te, stupor.

Def: Hemoly@c anemia,
acanthocytosis, muscle
weakness, posterior column and
spinocerebellar tract
demyelina@on (similar to B12 def
but without megaloblas@c

Made in intes@nal ora. Not present in breast
milk; neonates need injec@ons. Neonatal
hemorrhage with PT & PTT, normal
bleeding @me. May also occur a[er prolonged
use of an@bio@cs.

Deciency caused by an@bio@c use or
inges@on of raw eggs.
Def: Derma@@s, alopecia, enteri@s.

Cynthia Czawlytko
FA 2014