Miscellaneous Biochem Flashcards
Alpha-1 Antitrypsin Deficiency (AATD)
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
Alpha-1 Antitrypsin Deficiency (AATD): Features
•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
Canavan Disease
Inheritance: Autosomal recessive Gene: ASPA Deficient Enzyme: Aminoacylase 2 Excess metabolite: N-acetylaspartic acid (NAA) Metabolic testing: Elevated urine NAA
Canavan Disease: Major feautures
- 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
Hemochromatosis
Inheritance: Autosomal recessive
Gene: HFE
Excess metabolite: Iron
Metabolic testing: Elevated serum ferritin
Hemochromatosis: Major features
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
Smith-Lemli-Opitz syndrome (SLOS)
Inheritance: Autosomal recessive
Gene: DHCR7
Deficient enzyme: 7-dehydrocholesterol reductase
Excess Metabolite: 7-dehydrocholesterol (7DHC)
Metabolic testing: Elevated serum 7DHC
Smith-Lemli-Opitz syndrome (SLOS): Features
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
Wilson Disease
Kayser-Fleischer Rings Inheritance: Autosomal recessive Gene: ATP7B Deficient Enzyme: Ceruloplasmin Excess Metabolite: Copper Metabolic testing: High urinary/hepatic/serum copper, Low serum ceruloplasmin
Wilson Disease: Major Features
•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
Wilson Disease: Minor features:
- Renal problems
- Arthritis
- Pancreatitis
- Cardiomyopathy
- Sunflower cataracts