WILSON DISEASE

-

 


Aka Hepatolenticular degeneration 

Autosomal Recessive inheritance 

What is the defect in Wilson disease?

Basic defect in hepatocellular copper transport, leading to the accumulation of copper in the liver and other tissues, including the brain. 

ATP7B is a copper-transporting intracellular protein affected in Wilson disease. ATP7B is expressed mainly in hepatocytes. 

This defect leads to reduced incorporation of copper into apo ceruloplasmin and decreased transport of copper from the liver into bile, leading to copper excess in tissue. 

Although the ceruloplasmin levels are diagnostic in Wilson disease it does not play any significant role in the disease pathogenesis.

Note: Hereditary aceruloplasminemia is a disease condition characterized by iron deposition in tissues and not copper 

How copper deposition occurs in other tissues?

Once the hepatocytes are filled with copper this leads to injury thus liberating the copper in circulation which leads to extrahepatic copper deposition. 

Clinical features: 

Wilson disease present with hepatic, neurological and psychiatric manifestations.

Children usually tend to present more commonly with hepatic symptoms whereas adolescent and older patients have neurological manifestations 

What are the hepatic manifestations?

Hepatic manifestations can be asymptomatic with biochemical abnormalities or acute hepatic failure or acute hepatitis or chronic hepatitis and cirrhosis.

Patients of Wilson disease presenting with acute liver failure have often associated Coombs negative hemolysis.

How is acute hepatitis of Wilson different from infective hepatitis?

Presence of coombs negative hemolytic anemia 

Aminotransferases are elevated but as significant as infective hepatitis. AST:ALT >2

ALP is normal or subnormal. ALP:total bilirubin <4 

What are the neurological manifestations of Wilson disease?

Basal ganglia is affected in case of Wilson disease. 

Dysarthria is the most common neurological manifestation of Wilson disease. 

Other manifestations can be 

Dystonia

Chorea

Athetosis

Tremors 

Cognitive impairment - can be frontal syndrome or subcortical dementia 

KF ring or Kayser-Fleischer rings are present in 98% of neurological Wilson. 

What are KF rings?



Ocular manifestation of Wilson.

Present in 50% of hepatic Wilson and 98% of neurological forms.

It is an indicator of CNS copper deposition.

These are brownish deposits of Copper in Descemet's membrane. 

Slit lamp is required for visualizing but sometimes can be visible with naked eyes.

It is an important clinical clue for Wilson diagnosis. 

What other ocular manifestation is visible in Wilson?

Sunflower cataract sue to copper deposition in lens. 

What is the type of hemolysis seen in Wilson?

Coombs negative hemolysis

What are the renal manifestations of Wilson Disease?

Fanconi syndrome characterized by loss of amino acids, bicarbonate, glucose and proximal renal tubular acidosis 

Also, nephrolithiasis may occur secondary to distal renal tubular acidosis


Diagnosis of Wilson disease



Source: ESPGHAN Wilson guidelines 2018



Source: Uptodate




 


Comments

Post a Comment

Popular posts from this blog

TURNER SYNDROME

-
Image
What is the other name of Turner Syndrome? Ullrich-Turner syndrome  What is the m/c sex chromosome disorder in female? Turner syndrome and occurs in approximately 1 in 2000 to 1 in 2500 live female births. What are the genotypes of Turner syndrome? 45X monosomy in 45% of cases  45X mosaicism with normal cell line in 15% cases  X chromosome anomalies like - Isochromosome, Ring chromosome, Xp or Xq deletion Y chromosome mosaicism in 10-12% cases. What gene is responsible for short stature in Turner syndrome? SHOX (short stature homeobox-containing gene on the X-chromosome) is associated with short stature in Turner syndrome and in Leri-Weill dyschondrosteosis. What gene is responsible for gonadal insufficiency in Turner syndrome? BMP15 (bone morphogenetic protein 15 (BMP15) on the short arm of the X chromosome (Xp)). What is the frequency of the 45X karyotype at conception? 3% approx, but  99% of these are spontaneously aborted, accounting for 5–10% of all abortuses. Mosaics are found to
Read more

HYPOTHYROIDISM CLINICAL FEATURES

-
Image
     1.       What are the clinical features of congenital hypothyroidism in a newborn? The clinical manifestations are commonly subtle in newborns with congenital hypothyroidism (CH).   Newborns with CH may be asymptomatic because of presence of maternal T 4 (which contributes to approximately one-third of circulating T 4 in a newborn) and residual functioning thyroid tissue.   FEATURES AT BIRTH   The classical symptoms of congenital hypothyroidism include ·          lethargy, ·          hoarse cry, ·          feeding difficulty, ·          constipation not responding to treatment, and increased somnolence.   The characteristic signs of CH include ·          Prolonged neonatal jaundice, ·          Macroglossia, ·          Umbilical hernia, ·          Wide posterior fontanelle, ·          Hypotonia, ·          Dry skin, ·          Head circumference may be slightly increased d/t myxedema of brain ·          Hypothermia. ·          Hirsute for
Read more

Congenital Hypertrophic Pyloric Stenosis

-
Image
What are the parts of pylorus? The incisura angularis divides the stomach into a body to the left and a pyloric portion to the right. The sulcus intermedius further divides the pyloric portion of the stomach: the pyloric vestibule to the left, denoted by an outward convexity of the greater curvature. The pyloric antrum or pyloric canal to the right The pyloric antrum is 2.5 cm and terminates in pyloric orifice into duodenum.   What happens to the normal anatomical structural in CHPS? In infants with IHPS, the pyloric ring is no longer identifiable as a clearly definable separation between the normally distensible pyloric antrum and the duodenal cap. Instead, a channel of variable length (1.5–2.0 cm) corresponding to the pyloric canal separates the normally distensible portion of the antrum from the duodenal cap. ·          Infantile hypertrophic pyloric stenosis  was first fully described by  Harald Hirschsprung  in 1888. ·          IHPS VS CHPS - ????? IHPS is would b
Read more