Errors of metabolism

Hereditary deficiency of aldose B
AR
Fructose-1-phosphate accumulates
Decrease in available phosphate
Inhibition of gluconeo, glycogenolysis

Hypoglycemia, jaundice, cirrhosis, vomiting

Decrease intake of fructose and sucrose

Defect in fructokinase
AR
Benign, asymptomatic condition
Fructose cannot enter cells
Appears in blood and urine

Absence of galactose-1-phosphate uridyltransferase
AR
Accumulation of toxic substances galactitol in lens of eye

FTT, jaundice, hepatomegaly, infantile cataracts, MR

Exclude galactose and lactose from diet

AR
Galactitol accumulates if galactose is present in diet
Relatively mild condition

Galactose in blood and urine, infantile cataracts -- failure to tract, lack of social smile

Age-dependent or heridtary lactose intolerance
Loss of brush border enzyme

Bloating, cramps, osmotic diarrhea

Avoid dairy products/lactase pills

X-linked recessive
Most common urea cycle disorder
Usually presents early
Excess carbamoyl phosphate converted to orotic acid

Orotic acid in blood and urine, decreased bun, hyperammonemia

AR

Decreased phenylalanine hydroxylase or decreased tetrahydrobiopterin cofactor
Tyrosine cannot be made

MR, growth retardation, seizures, fair skin, eczema, musty body odor

Decrease phenylalanine and increase tyrosine in diet

Lack of proper dietary therapy during pregnancy

Infant with microcephaly, MR, growth retardation, congenital heart defects

Homogentisic acid oxidase deficiency
AR
Defect in degradative pathway for tyrosine
Benign

Dark connective tissues, pigmented scera, urine turns black on standing
May have debilitating arthralgias

Deficiency in
Tyrosinase - cannot make melanin from tyrosine -- AR
Tyrosine transporters - decreased tyrosine supply

Can also result from lack of migration of neural crest cells

Increased risk of skin cacner

AR
Excess homocysteine, cystine becomes essential
1. Cysathionine synthase deficiency (give cys, b12, restrict met)
2. Decreased affinity of cystathione synthase for pyridoxal phosphate (give B6)
3. Homocysetine methyltransferase deficiency

MR, osteoporosis, tal stature, kyphosis, lens subluxation, atherosclerosis

Defect in dibasic AA transporter
(cystein, ornithine, lysine, arginine)
AR
Cystine kidney stones

Give acetazolmide to alkalinize urine

Blocked degradation of branched amino acids (Ile, Leu, Val)
Decrease alpha ketoacid dehydrogenase

Severe CNS defects, MR, Death

Excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase
Prevents DNA synthesis
Decreases lymphocyte
Cause of SCID

Absence of HGPRT
Defective purine salvage
Hypoxanthine to IMP and guanin to GMP
Results in excess uric acid production

MR, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis

Deficiency in orotic acid phosphoribosyltranferase or orotidine 5-phosphate decarboxylase
Can't convert orotic acid to UMP
Can't make pyrimidines
AR

Orotic acid in urine
Megaloblastic anemia
FTT

Give uridine

Type I glycogen storage disease
Glucose-6-phosphatase deficiency
Severe fasting hypoglycemia
Increased glycogen in liver
Increased lactate
Heptomegaly

Type II glycogen storage
Deficiency in alpha 1,4 glucosidase (acid maltase)
Cardiomegaly and systemic findings leading to early death

Type III glycogen storage
Deficiency in debranching enzyme (alpha 1,6 glucosidase)
Milder form of type I
Normal blood lactate levels
Gluconeogenesis intake

Type V glycogen storage idsease
Deficiency in skeletal muscle glycogen phosphorylase
Increased glycogen in muscle, cannot be broken down
Painful muscle cramps
Myoglobuinuria with strenuous exercise

Deficiency in alpha galatosidase A
Accumulates ceramide trihexoside
XR
Peripheral neurophathy of hands/feet, angiokeratomas, CV/renal disease

Deficiency in B-glucocerebrosidase
Glucocerebroside accumulates
AR
HSM, aseptic necrosis of femur, bone crises, macrophages that look like crumpled tissue paper

Most common lysosomal storage disease

Deficiency in sphingomyelinase
Sphingomyelin accumulates
AR
Progressive neurodegeneration, HSM, cherry red spot on macula, foam cells

Deficiency in hexoaminidase A
GM2 ganglioside accumulates
AR
Progressive neurodegeneration, developmental delay, cherry red spot on macula, lysomes with onion skin

Deficiency in galactocerebrosidase
Galactocerebroside accumulates
AR
Peripheral neuropathy, developmental delay, optic atrophy, globoid cells

Deficiency in arylsulfatase A
Cerebroside sufate accumulates
AR
Central and peripheral demyelination with ataxia, dementia

Deficiency in alpha-L-iduronidase
Heparan sulfate and dermatan sufate accumulate
AR
Developmental delay, gargoylism, airway obstruction, corneal clouding, HSM

Deficiency in iduronate sulfatase
Heparan sulfate, dermatan sufate accumulate
XR
Milder hurlers + aggressive behavior -- eyes okay