Pathology 3500 Lecture 18: Metabolic & Nutritional Diseases I
1 May 2018
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Lecture 003: Metabolic & Nutritional Diseases I
Metabolic Disorders
● Disorder in the metabolism, use or storage of amino acids, carbohydrates or fats
● Metabolism: a range of biochemical process that take place in an living organism
○ Consists of catabolism (breaking down) and anabolism (building up)
○ Metabolism is commonly referring to the breakdown of carbohydrates, amino
acids, and lipids for energy
Genetic Metabolic Disorders (involuntary)
● Rare
● Due to:
○ Enzyme deficiency
■ Blocking of metabolism
○ Accumulation of substances prior to the metabolic block
○ Production of toxic metabolites
● Can test amniotic fluid before birth to screen for these disease
● Characterized by an autosomal recessive transmission
● Clinical expression
○ Neurological complication
■ Focal abnormalities
■ Mental retardation
○ Large variation in age of onset, rate of progression, etc
1. Phenylketonuria (PKU)
● Autosomal recessive disease
● 1 in 12,000 live birth
● Phenylalanine hydroxylase, enzyme that converts phenylalanine to tyrosine is
deficient
○ Amino acid metabolism disorder
● Patient is normal at birth but symptoms manifest as phenylalanine accumulates
● High blood levels of phenylalanine
○ Impairs brain development
■ Neurons are hypomyelination, gliosis, microcephaly and no lysosomal
storage
○ Increase urinary excretion of phenylpyruvic acid
○ Mental retardation
○ Seizures
○ Hyperactivity
○ Decreased pigmentation (less melanin production)
○ Musty body odor
● Treatment
○ Can be detected by screening (Guthrie test-serum analysis)
○ Restricting phenylalanine in the diet and taking tyrosine supplements
find more resources at oneclass.com
find more resources at oneclass.com
● Essential that maternal phenylalanine levels in female PKU patients be lowered by
dietary restriction prior to conception to avoid complication in the fetus
○ Phenylalanine is a teratogen
○ Babies is normal at birth but later fail to meet the milestone
○ Babies profoundly mentally retarded and have multiple congenital anomalies
2. Galactosemia
● Autosomal recessive
● 1 in 60,000
● Disorder of carbohydrate metabolism
○ Deficiency of galactose-1-phosphate uridyl transferase (GALT)
■ Enzyme helps convert galactose (metabolized from lactose) into glucose
○ Lead to accumulation of galactose-1-phosphate
■ Galactosuria
■ Hypergalactosemia
● Metabolites of galactose accumulates in many tissue
○ Liver, spleen, kidney, cerebral cortex and the lens of the eye
● Symptoms
○ Jaundice
○ Liver damage
■ Fatty change
■ Scarring
■ Hepatomegaly
○ Cataracts
○ Neuronal damage
■ Nerve cell loss
■ Gliosis
■ Edema
○ Kidney damage
■ Aminoaciduria
■ Lack of galactose impares amino acid transport in the kidney
○ Mental retardation
○ Speech and neurological defects
○ Babies exhibit failure to thrive
■ Normal at birth
■ But doesn’t reach milestones
● Diagnosis
○ Assay of transferase in WBC or RBCs
○ Antenatal diagnosis via enzyme assay or DNA analysis are available
● Treatment
○ Dietary therapy (remove galactose from the diet)
3. Lysosomal Storage Diseases
● Over 40 lysosomal storage diseases have been identified
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find more resources at oneclass.com
● Rare
● Autosomal recessive
● Lysosome break down complex compounds into simple compounds
○ Sphingolipids and mucopolysaccharides into soluble end products
● Lack of lysosomal enzymes
○ Catabolism of the substrate remains incomplete
○ Accumulation of partially degraded insoluble metabolites within the
lysosomes
○ Lysosome swell
■ Cytostome is expanded
● Clinical expression
○ Variable in infants and children
■ Symptoms appear quite early
○ Progressive mental, motor deterioration, death
○ Milder form with adult onset
4. Tay-Sachs Disease (GM2 Gangliosidosis)
● Deficiency of hexosaminidase A (subunit)
○ Needed to degrade GM2
● Accumulation of ganglioside/GM2 within the neurons, axon and glial cells through the
CNS occurs
○ Cells appear swollen or “foamy” with lipid vacuolation
● Most common in Ashkenazi Jews
○ 1 in 30 are heterozygous carriers
● Diagnosis
○ Estimating the level of hexosamines in the serum
○ DNA analysis
● Prognosis
○ Infants appear normal at birth
○ Motor weakness, mental retardation, blindness, severe neurologic dysfunction
○ Death in 2-3 years
● Treatment
○ No good treatment
5. Niemann-Pick Disease
● Deficiency of acid sphingomyelinase
○ Accumulation of sphingomyelin
● Type A
○ Breakdown of sphingomyelin into ceramide and phosphorylcholine is impaired
■ Excess sphingomyelin accumulates in the phagocytic cells and neuron
○ Affects: spleen, liver, bone marrow, lymph nodes and lungs
■ All have high amount of histiocytes/phagocytic cells
○ CNS is involved
■ Neurons are enlarged and vacuolated
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Disorder in the metabolism, use or storage of amino acids, carbohydrates or fats. Metabolism: a range of biochemical process that take place in an living organism. Consists of catabolism (breaking down) and anabolism (building up) Metabolism is commonly referring to the breakdown of carbohydrates, amino acids, and lipids for energy. Accumulation of substances prior to the metabolic block. Can test amniotic fluid before birth to screen for these disease. Large variation in age of onset, rate of progression, etc: phenylketonuria (pku) Phenylalanine hydroxylase, enzyme that converts phenylalanine to tyrosine is deficient. Patient is normal at birth but symptoms manifest as phenylalanine accumulates. Neurons are hypomyelination, gliosis, microcephaly and no lysosomal storage. Can be detected by screening (guthrie test-serum analysis) Restricting phenylalanine in the diet and taking tyrosine supplements. Essential that maternal phenylalanine levels in female pku patients be lowered by dietary restriction prior to conception to avoid complication in the fetus.
