Miscellaneous Biochem

Question 1

Alpha-1 Antitrypsin Deficiency (AATD)

Answer 1

Inheritance: Autosomal recessive
Gene: SERPINA1
•Due to knowledge of protease inhibitors before knowledge of the gene, most common pathogenic mutation is referred to as PIZ (PIM is the most common normal allele)

Deficient Enzyme: Alpha-1 antitrypsin (A1AT)
Excess Metabolite: -decreased A1AT in the lungs, increased abnormal A1AT protein in the liver
Metabolic testing: Low serum A1AT

Question 2

Alpha-1 Antitrypsin Deficiency (AATD): Features

Answer 2

•COPD with otherwise unknown etiology
•Liver disease at any age
•C-ANCA positive vasculitis (C-ANCA is a substrate of A1AT)
•Necrotizing panniculitis
o Inflammation of the fatty fibrous tissue directly beneath the skin

Question 3

Canavan Disease

Answer 3

Inheritance: Autosomal recessive
Gene: ASPA
Deficient Enzyme: Aminoacylase 2
Excess metabolite: N-acetylaspartic acid (NAA)
Metabolic testing: Elevated urine NAA

Question 4

Canavan Disease: Major feautures

Answer 4

• Classic triad of hypotonia, head lag, and macrocephaly
• Leukodystrophy
• Symptoms onset in infancy and progress rapidly
• Intellectual disability
• Motor skill regression
• Feeding difficulties
• Hypo- or hypertonia
• Poor head control
• Macrocephaly
• Paralysis
• Blindness
• Seizures
• Shortened lifespan (teens)

Milder form exists with mild developmental delay
No treatment currently exists

Question 5

Hemochromatosis

Answer 5

Inheritance: Autosomal recessive
Gene: HFE
Excess metabolite: Iron
Metabolic testing: Elevated serum ferritin

Question 6

Hemochromatosis: Major features

Answer 6

Major features:
•Hepatomegaly
•Cirrhosis
•Hepatocellular carcinoma
•Diabetes
•Cardiomyopathy
•Hypogonadism
•Arthritis
•Progressive increase in skin pigmentation

Treatment:
•Low iron diet
•Therapeutic phlebotomy
•Liver transplant may be required if it has incurred substantial damage

Question 7

Smith-Lemli-Opitz syndrome (SLOS)

Answer 7

Inheritance: Autosomal recessive
Gene: DHCR7
Deficient enzyme: 7-dehydrocholesterol reductase
Excess Metabolite: 7-dehydrocholesterol (7DHC)
Metabolic testing: Elevated serum 7DHC

Question 8

Smith-Lemli-Opitz syndrome (SLOS): Features

Answer 8

Moderate-to-severe intellectual disability
•Microcephaly
•Behavioral problems
     oAggression
     oSelf-injury
     oAutism
•Sensory hypersensitivity
•Strabismus, cataracts, functional eye abnormalities
•Congenital heart defects
•GI issues
•Pyloric stenosis
•Feeding difficulties
•Renal anomalies
•Dysmorphic features
    o2,3-syndactyly of the toes
    oPostaxial polydactyly of the hands or feet
    oAmbiguous genitalia
    oHypospadias
    oBitemporal narrowing
    oShort, upturned nose
    oPtosis 
    oMicrognathia
    oEpicanthal folds
   oCapillary hemangioma of the nose

Question 9

Wilson Disease

Answer 9

Kayser-Fleischer Rings
Inheritance: Autosomal recessive
Gene: ATP7B
Deficient Enzyme: Ceruloplasmin
Excess Metabolite: Copper
Metabolic testing: High urinary/hepatic/serum copper, Low serum ceruloplasmin

Question 10

Wilson Disease: Major Features

Answer 10

•Liver disease
  oRecurrent jaundice
  oHepatitis
  oFatty liver
  oHemolytic anemia
•Neurologic disease
  oTremors
  oPoor coordination
  oLoss of fine motor control
  oChorea
  oSpastic dystonia
•Psychiatric manifestations
  oDepression
  oAggression
  oPhobias
  oAntisocial behavior
  oPoor memory
  oShortened attention span
•Kayser-Fleischer rings – visible on eye

Question 11

Wilson Disease: Minor features:

Answer 11

• Renal problems
• Arthritis
• Pancreatitis
• Cardiomyopathy
• Sunflower cataracts