Metabolic Disorders: Mucopolysaccharide, Purine, and Carbohydrate Disorders Flashcards
• caused by a deficiency of an enzyme responsible for the degradation of a metabolic product, whose accumulation results in lysosomal malfunction and disease
• Accumulation of incompletely metabolized polysaccharide portions (acid mucopolysaccharides or glycosaminoglycans) in the lysosomes of connective tissues and excreted in urine
MUCOPOLYSACCHARIDE DISORDERS
Best known mucopolysaccharidoses:
Hurler syndrome,
Hunter syndrome, and
Sanfilippo syndrome
MUCOPOLYSACCHARIDE DISORDERS
• molecular defect in ____ disease is in the activity of a-L-iduronidase
HURLER SYNDROME
MUCOPOLYSACCHARIDE DISORDERS
• Abnormal skeletal structure
• Severe mental retardation
• ‘steamy’ cornea
HURLER
MUCOPOLYSACCHARIDE DISORDERS
• presence of nodular or pebbly skin lesions, most characteristically over the scapular area, the upper arms or the lateral aspects of the thighs
HUNTER SYNDROME
MUCOPOLYSACCHARIDE DISORDERS
• Patients with the severe form may appear identical to those with Hurler disease except for the absence of cloudy corneas
HUNTER SYNDROME
MUCOPOLYSACCHARIDE DISORDERS
• molecular defect is in the enzyme iduronate sulfatase
HUNTER SYNDROME
MUCOPOLYSACCHARIDE DISORDERS
• Exclusive excretion of heparan sulfate
SANFILIPPO SYNDROME
MUCOPOLYSACCHARIDE DISORDERS
• degeneration of the central nervous system (CNS), resulting in mental retardation and hyperactivity, typically commencing during childhood
SANFILIPPO SYNDROME
MUCOPOLYSACCHARIDE DISORDERS
• associated with a progressive and severe loss of intellectual processes (such as speech) and motor functions (including walking and swallowing) then ultimately regress to a vegetative state until death
Sanfilippo syndrome
MUCOPOLYSACCHARIDE DISORDERS
This results in accumulation of partially metabolized polysaccharides in lysosomes of connective tissue cells and increased excretion in urine.
🚨 Commonly Found in Urine: (3)
✔️ Dermatan sulfate
✔️ Keratan sulfate
✔️ Heparan sulfate
Mucopolysaccharide disorders
📌 Common Screening Tests:
• Acid-albumin turbidity test 🧪
• Cetyltrimethylammonium bromide (CTAB) turbidity test
Purine Disorders
• Massive excretion of urinary uric acid crystals
• alert: increased uric acid crystals in pediatric urine specimens
Lesch-Nyhan disease
Purine Disorders
• first sign is usually the appearance of orange crystals or orange sand in the diapers
Lesch-Nyhan disease
Purine Disorders
• Characterized by hyperuricemia, neurodevelopmental abnormalities with global developmental delay, involuntary movements, and self-injurious behavior
Lesch-Nyhan disease
PURINE DISORDERS
Lesch-Nyhan disease
• deficiency of________, the enzyme is responsible for recycling purines
• causes an increase in guanine and hypoxanthine,* which eventually gets converted into uric acid
hypoxanthine-guanine phosphoribosy transferase
PURINE DISORDERS
• deficiency of hypoxanthine-guanine phosphoribosy transferase, the enzyme is responsible for recycling purines
Lesch-Nyhan disease
PURINE DISORDERS
• self-destructive biting of the lips and fingers
• patients bite with a ferocity that leads to significant loss of tissue
• relative deficiency of GTP in HPRT deficiency, resulting in decreased dopamine receptor activation
• Lesch-Nyhan disease
PURINE DISORDERS
• Excess uric acid is known to precipitate in kidneys and joints, resulting in renal calculi and tophi
• Lesch-Nyhan disease
PURINE DISORDERS
Mutation in the_______ → Deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT)
• Leads to uric acid accumulation throughout the body.
HPRT1 gene
Carbohydrate Disorders
______: presence of sugar in urine
• Primary concern:_____
• Others:
_____ (may be seen in pregnancy and lactation)
______ (parenteral feeding)
______ (ingestion of large amounts of fruit)
Melituria
galactosuria
lactosuria
fructosuria
pentosuria
• In classic galactosemia, the enzyme that is reduced or missing is called_______ which enables the body to break down galactose into glucose
galactose-1-phosphate uridyl transferase (GALT)
• an inborn error of carbohydrate metabolism characterized by elevated levels of galactose and its metabolites due to enzyme deficiencies
GALACTOSEMIA
GALACTOSEMIA
• Accumulation of galactose in the body is not good
• feeding problems, failure to thrive (most common initial clinical symptom), hepatocellular damage, bleeding, and sepsis in untreated infants which lead to mental retardation
• in approximately 10% of individuals,______ are present
cataracts
GALACTOSEMIA MANAGEMENT
• Dietary elimination of…
• Alternative:…
milk and milk products containing lactose
soy-based formula
