Liver d is ea s e + Pa rk in s on ia n trem or + Fa n con i s yn d rom e.
Wilson disease
Fever and cutaneous skin eruptions after starting therapy for Wilson disease.
D-penicellamine hypersensitivity reactions
A patient with recently diagnosed Wilson disease is started on D-penicillamine therapy to manage serum copper levels.
The patient develops a fever and cutaneous skin eruptions within days. He presents for evaluation and is found to have new lymphadenopathy on physical exam.
Laboratories reveal new thrombocytopenia and neutropenia.
What happened here?
How should this patient be managed, both acutely and chronically?
- this is D-penicellamine hypersensitivity reactions
*Acute… stop D-penicellamine
*Chronic…
the next step is to use an alternative chelating agent or zinc salts (or both).
Trientine is less potent than D-penicillamine but has a much less side-effect , and in many patients, trientine is as effective as D-penicillamine.
Acute hepatitis + Hemolytic anemia + Low alkaline phosphatase (ALP).
Wilson
Hepatitis + Hypouricemia + Ma llory bodies.
Wilson
Liver problems associated with risus sardonicus and micrographia.”
Wilson
من طرف المعلقة
Low ALP levels (not high ones) and low serum uric acid levels may occur in symptomatic liver or neurologic disease due to Fanconi syndrome of the proximal renal tubules.
من طرف المعلقة
The presence of neurologic findings is almost with cirrhosis — it’s very unusual to have neurologic findings in the absence of cirrhosis.
من طرف المعلقة
Kayser-Fleischer (KF) rings occur from deposition of copper in the Descemet’s membrane of the inner cornea, whereas the characteristic “sunflower cataract” is from copper deposition in the lens capsule.
من طرف المعلقة
Although 95% of patients with WD have depressed serum ceruloplasmin levels (<20 mg/dL) and 85% have elevated urine copper excretion (>100 mcg/24 hrs), low ceruloplasmin and high urine copper are sensitive but not entirely specific for WD because both are seen in some asymptomatic heterozygotes, among other conditions.
من طرف المعلقة
The gold standard for diagnosis remains quantification of hepatic copper, where a concentration above 250 mcg copper/g
من طرف المعلقة
It’s vital to screen first-degree family members of affected individuals with slit-lamp examination and measurement of serum ceruloplasmin levels.
من طرف المعلقة
Both neurologic symptoms and liver tests may initially worsen after starting therapy (more so with D-penicillamine than trientine), but subsequent improvement typically occurs within 6 months of starting therapy
من طرف المعلقة
Wilson’s Disease (WD) happens in young people, so if a Board question features a patient over 60 years of age, it’s essentially incompatible with WD — don’t be fooled.
Fulminant liver failure + markedly depressed ALP.
Wilson
ماذا تعرف عن ATP7B
- The ATP7B gene is agene carried on chromosome 13 responsible for copper metabolism..
ازاي؟
1- Increase copper excretion in bile.
2-convert copper into ceruloplasmin. - So, Defects in the ATP7B gene mutation will lead to
1- decreased copper excretion in bile, leading to increased copper levels in hepatocytes and other organs such as the brain, kidney, and eye.
2- There is a decreased level of serum ceruloplasmin (typically < 20 mg/dL).
أمتي اشك في wilson
Age of onset is typically between 3 and 40 years.
+
1-unexplained. :
*Increase alt,ast
*Chronic hepatitis
*Cirrhosis
*Hepatic failure with decreased alkp <40
2-unexplained neurological features (microgra6,drolling, Parkinson’s like symptoms, depression, decrease school performance)
3-unexplained psychiatric disorders
4-Asibling or parent died suddenly in young age.
5-children with unexplained GB black pigment stone
6-unexplained acquired coombs -ve hemolytic .
7-kayser flesher ring on routine eye exam
Symptoms of Wilson
BLACK
1-B…Brain…Basal ganglia deposition of copper leading to
neuropsychiatric disorders
* Dysarthria,
* dystonia
*drooling
* jerky movements, mask-like facies, rigidity, like Parkinson’s features.
* Depression
* Decreased School performance
* Micrographia
* Associated ← Kayser Fleisher ring and cirrhosis
← Improve with Copper Chelation
Symptoms of Wilson
L…Liver
- Cirrhosis in young age
- Chronic hepatitis
- Fulminant “ Acute liver failure
+ Alkaline phosphatase < 40
↑ ALT, AST but ast/alt >2.2
↑ Bilirubin ,but alkp/bill <4
↑ 24h urinary Copper
Ceruloplasmin
طبيعي أو قليل
* Auto immune hepatitis - like (ممكن يكون صعب التفريق ويحتاج فحص النحاس)
* Fatty liver is common in Wilson (ممكن يتشخص غلط على أنه NASH)
آمل
Symptoms of Wilson
A
*Azure lunulae
*Acute intravascular hemolysis
negative Coombs test ascociated mostly with acute liver failure or chronic hepatitis.
*Arthropathy,osteopenia
Symptoms of Wilson
C…
Corneal →
* Kayser Fleischer Ring (Copper deposits in Descemet’s membrane of cornea)
* occur mostly in symptomatic → greenish - brownish or golden
* visible by slit lamp especially in neuropsychiatric
* Not Pathognomonic as it is also seen in other causes of long standing cholestasis
* Sunflower Cataract (Copper deposition in lens)
* Not interfere much with vision
* Improve faster than kayser flesher ring
Symptoms of Wilson
K..
Kidney →deposits in proximal renal tubules
* Fanconi Syndrome
* Amino-aciduria,hyperphosphaturia, glycosuria, uricosuria
* Proteinuria is a manifestion of WD but Nephrotic proteinuria & Good Pasture’s are not a common S.E of D- Penicillamine (بتبقي اكتر من 1000)
Diagnosis of Wilson
جملة للتاريخ
Serum Ceruloplasmin < 20 is diagnostic + Kayser flesher ring +↑ 24h urinary copper > 100 is diagnostic
Diagnosis of Wilson
1-Ceruloplasmin test < 20 (N is 20-40)
* The initial test in WD diagnosis
* But ↓ alone not Pathognomonic for WD because:
* It can ↓ also in children up to 2 years.
* End Stage liver disease
* Hereditary aceruloplasminemia
* Heterozygous WD carrier gene
* Also, S. Ceruloplasmin is acute phase reactant which may ↑ in:
* infection
* pregnancy
* Estrogen OCP
* Biliary obstruction
