Adult-onset Disorders Flashcards
What is the genetic cause of Alpha 1 Antitrypsin deficiency?
Codominant
SERPINA1 gene (AAT protein)
What are the clinical features of Alpha 1 Antitrypsin deficiency?
Emphysema (Chronic Obstructive Pulmonary Dz
COPD)
Liver disease at any age
Neonatal cholestasis
Vasculitis
Necrotizing panniculitis
What is the age of onset of Alpha 1 Antitrypsin deficiency?
40-50y if smoker
60’s if not
What is the PI*M allele in Alpha 1 Antitrypsin deficiency?
Normal allele
What is the PI*Z allele in Alpha 1 Antitrypsin deficiency?
Most common pathogenic allele
Homozygotes have severe disease
Most common: p.Glu342Lys
What is the PI*S allele in Alpha 1 Antitrypsin deficiency?
A pathogenic allele causing functionally deficient AAT
Usually only of clinical consequence when in combination with PIZ (PISZ)
What is the main function of the AAT protein?
Protection of the lung from proteolytic damage by inhibiting neutrophil elastase
What is the variant in SERPINA1 that is present in almost 95% of cases?
p.Glu342Lys
What is the management of Alpha 1 Antitrypsin deficiency?
Immunizations (Hep A, B, influenza, Pneumo, COVID)
Smoking cessation
COPD with standard therapy
Organ transplant
Pulmonary rehab
Augmentation therapy–IV of pooled human serum AAT in emphysema
What are the presenting features in Alpha 1 Antitrypsin deficiency?
- Neonatal jaundice (17%)
- Young adult smoke or older adult smoker with lower lobe emphysema
- Cryptogenic liver disease
What are the lab findings in POI?
Elevated FSH
Low estradiol levels
Amenorrhea for 3 to 4 months
What is the genetic cause of hemochromatosis?
HFE gene
(AR)
What is the prevalence of the p.Cys282Tyr (C282Y) HFE variant in non-Hispanic whites?
1:200 to 1:400
Why do all HFE homozygotes not develop hemochromatosis?
Low Penetrance
What is are the clinical signs of HFE hemochromatosis?
Inappropriately high iron absorption by the GI mucosa leads to excessive iron storage in the liver, skin, pancreas, heart, joints, and testes
Early Sx: abdominal pain, weakness, lethargy, and weight loss
What is the genetic cause of Wilson disease?
ATP7B gene (AR)
What are the clinical features of Wilson disease?
Age onset: 3-50 years
Liver disease–jaundice, hepatitis
Neurological: movement disorder, disorganization of personality
Kayser Fleisher Ring
What are the labs in Wilson disease?
Low serum copper
Low ceruloplasmin
Increased urinary copper excretion
Liver bx: increase copper storage
What is the treatment of Wilson disease?
Diet
Chelating agents
Liver transplant
What percentage of AD patients don’t have an APOE e4 allele?
42%
What is the risk of a sibling of a proband with AD (with limited family hx)?
20-25%
What is the general population risk for AD?
10-15%
What are the symptoms of Parkinson disease?
Tremor
Rigidity
Shallow, shuffling gait
Nonmotor symptoms: poor sleep, dementia, psychosis
What is the age of onset of PD?
Juvenile: <20 years
Early onset: 20-50 years
Late onset: >50 years
What percentage of PD patients have family history?
15%
What is the lifetime risk for late-onset PD?
4%
What are the genes associated with PD?
GBA (AD): more common in AJ
Parkin (AR): early onset
PINK1 (AR): early onset
LRRK2 (AD): African Berber
What is Thrombophilia?
Predisposition to develop blood clots
Deep vein thrombosis
Pulmonary embolus
What are some of the thrombophilia disorders?
Factor V Leiden
Prothrombin
(MTHFR)
Protein C, Protein S, Antithrombin III
