Dr Samuel Alexander Kinnier Wilson (1878–1937), U.S.-born British neurologist best known for his description of Wilson's disease.
In his treatise, he is credited for introducing the term "extrapyramidal" into neurological medicine.
Hacia mencion a la condicion hereditaria, coocurrencia de cirrosis hepatica y deficit neurologico y el predominio de st y sg extrapiramidales.
Gen ubicado en brazo largo q de cromosoma13, en posicion 14.3. ATP7B es un gen relativamente largo, de 80 kb y 21 exones.
These defects include insertion, dele- tion, splice site and point mutations
Genes modificadores explicarian variabilidad, que determina los niveles individuales de tolerancia y capacidad de almacenamiento de cobre.
Segun grupos etnicos, una o unas pocas mutaciones son frecuentes, y tener conocimiento de ellas ayuda en el screening para encontrar estas mutaciones
Europa: C: citosina A: adenina sustitución de una histidina por glutamato en la posición 1069 (H1069Q
Absorción en intestino delgado por hCTR1 (transportador de cobre 1). Una vez captado por enterocitos duodenales puede unirse a proteinas intracelulares (metalotioneinas) o ser exportado al exterior a traves de la proteina transportadora ATP7A. Deficit produce no absorcion de cobre provovando enfermedad de Menkes, ligada a cr X.
Una vez en la sangre, se une a la albumina o histidina para ser transportado al higado, donde ingresa al enterocito por la hCTR1.
En la BHE, las prot ATP7A y B median la entrada y salida de cobre al LCR respectivamente.
Copper absorption occurs in the small intestine via enterocyte uptake by human copper transporter 1 (hCTR1) and passage into the blood mediated by ATP7A at the basolateral aspect of duodenal epithelia. Copper is conveyed to the liver via the portal circulation and excess copper is removed by excretion into the bile at the apical aspect of hepatocytes, a process impaired by mutations in ATP7B. Copper diseases of the liver also involve mutations in the AP1S1 gene implicated in MEDNIK syndrome, the acetyl CoA transporter SLC33A1, and the cytosolic copper chaperone CCS. Mutations in the manganese transporter SLC30A10 produce hepatic cirrhosis due to manganese accumulation that can mimic Wilson’s disease. ATP7A and ATP7B are believed to mediate copper entry and exodus, respectively, at the blood–CSF barrier of the choroid plexus epithelia. Brain copper deficiency (Menkes disease) or excess (Wilson’s disease), respectively, result from mutations in these essential copper transporters. The CNS is also affected by alterations in AP1S1, SLC33A1, CCS, and SLC30A10. Isolated motor neuron degeneration occurs in association with unique ATP7A missense mutations affecting axonal trafficking, and sensory peripheral neuropathy can be a component of Wilson’s disease. MEDNIK=mental retardation, enteropathy, deafness, neuropathy, ichthyosis, and keratodermia.
MENKES: disease typically presents in boys at age 2–3 months, with a subsequent loss of previously obtained developmental milestones and the onset of hypotonia, seizures, and failure to thrive. White matter abnormalities on MRI show impaired myelination. Diffuse brain atrophy, ventriculomegaly, and tortuosity of the cerebral vasculature are also present. Without early treatment, death usually occurs several years after onset.
Los primeros son estudios de 1984, basados en suposiciones
Tanto portador y poca enfermedad se explicaria por baja penetrancia de las mutaciones en ATP7B
Subdiagnosticado
Necrosis, gliosis y cambios quisticos.
Riñon: acidosis tubular renal, nefrolitiasis
OJOS: KF y cataratas en girasol
Con la progresion, degeneracion vacuolar en tubulo proximal del riñon (Sd Fanconi) y anillo de KF
3 sindromes clínicos : Distónico, Atáxico, Parkinsoniano . Lo mas comun es la combinacion de sds
bnormal vertical smooth pursuit has been reported in 85% of patients with Wilson’s disease on formal testing with electro-oculography, but vision was normal.
La risa sardónica consiste en una retracción del labio superior y en una apertura de la boca por una distonía de los músculos faciales y es una característica muy típica de la EW, asociada fundamentalmente a lesiones del putamen.
Anillo KF: Anillo color café amarillento en limbo corneal, causado por deposito de cobre en membrana de Descemet de la cornea. Se encuentra en 95% neurologicos y 50-60% en pacientes hepaticos
Mientras más joven, mayor compromiso hepático
Necesita validacion clinica
Anillos KF: Oftalmologo con lampara de enhendidura ( tb prsentes en CBP)
FN ceruloplasmina: ACO; FP:insuficiencia hepatica
Cupruria en 24 hrs >100 ug/ 24 hrs es tipico de EW.
Representative T2-weighted axial brain MRI scan showing symmetrical T2-weighted hyperintense lesions (solid green arrows) in the tectal midbrain on the left and in the ventromedial thalami and posterior limbs of the internal capsule on the right
Cara de panda: hiperintensidad en tegmento mesencefalico a excepcion de nucleo rojo y pars reticulata de sust nigra.
penicillamine treatment because of marked side-effects. These included nephrotoxicity, haematological abnormalities, and elastosis perforans serpiginosa (usually on the neck and axillae).59 Adverse events associated with trientine and tetrathiomolybdate use include bone marrow toxicity, whereas zinc therapy is often associated with gastrointestinal discomfort. Independent of the chosen medical regimen, non-adherence or discontinuation of medical therapy is associated with the risk of intractable hepatic decompensation.
The mechanism of this neurological deterioration is not fully understood, but seems to be related to dose, given that a high starting dose could increase the risk of rapid chelator-induced paradoxical worsening. To mechanistically understand these dose effects, a concept of different copper pools has emerged that differentiates between high-affinity bound copper (bound to ceruloplasmin) and free copper (not bound to ceruloplasmin). A plausible mechanism of the paradoxical neurological deterioration could be over- mobilisation of copper by chelator therapy, leading to an increased free copper pool with toxic effects.
Skin laxity in a 18 year-old patient with occipital horn syndrome.b) MRA showing tortuosity of cerebral arteries (arrow). c-d) Occipitalhorns are shown in a skull X-ray (c) and MRI T1 WI (d) (arrows).
