MAINTAINANCE THERAPY

• If once patients have been decoppered, they can be switched to maintenance therapy.
• Prior to switching to maintenance therapy, patients should be clinically well, have stable and either normal or near normal serum aminotransferases and hepatic synthetic function, a normal nonceruloplasmin-bound copper concentration and 24-hour urinary copper repeatedly in the range of 200 to 500 µg (3 to 8 µmoles) per day on treatment.
• Most patients require one to five years of therapy to achieve these goals
FULMANENT HEPATIC FAILURE DUE TO WD
• If patient has fulminant hepatic failure, initial treatment must be aimed at the rapid removal of copper.
• Although hemodialysis, peritoneal dialysis, and hemofiltration have been used, plasma exchange with fresh frozen plasma replacement may be preferred since it can remove relatively large amounts of copper in a short period of time.
• Hemofiltration and albumin dialysis have also been described as temporizing measures
PREGNANCY
• Pregnant women with WD can have a successful pregnancy while undergoing chelation therapy.
• These patients should continue on the same agent but with a slightly reduced dosage, particularly in the third trimester.
• Abrupt cessation of the drug treatment can be fatal.
• If the patient is completely free of toxic copper, she should be advised to take only zinc salt.
• Although D-penicillamine and trientine are potentially teratogenic, there are currently insufficient data concerning their teratogenic effects in pregnant patients with WD to warrant cessation of treatment
Symptomatic Treatment
• Symptomatic treatment for dystonia and parkinsonian features, psychiatric disturbances, and encephalopathy can be very successful and reassuring for the patient with WD.
• The treatment of dystonia and parkinsonian features includes the administration of anticholinergics, tizanidine, baclofen, levodopa, or γ-aminobutyric acid (GABA) agonists—particularly clonazepam. Comparative studies of the use of these medications for symptomatic therapy are, however, lacking
• Botulinum toxin injection is a useful adjunct therapy in cases with severe limb dystonias when other treatments are unsuccessful.
• Convulsions can be controlled with both traditional and newer antiepileptic drugs; in our opinion, more than one drug is often required to achieve control.
• Psychiatric disturbance is usually managed with atypical neuroleptics, and occasionally with traditional neuroleptics.
• Hepatic encephalopathy is managed with a standard regimen of protein restriction and lactulose.
ASYMPTOMATIC PATIENTS
• For asymptomatic or presymptomatic patients identified through family screening, treatment with a chelating agent, such as d-penicillamine [189] or with zinc is effective in preventing disease symptoms or progression [190].
• Whether d-penicillamine or zinc should be used in presymptomatic children under the age of 3 years has not been determined.


HEPATIC TRANSPLANTATION
• In patients with progressive liver failure or acute liver failure from fulminant hepatitis with or without intravenous hemolysis, orthotropic hepatic transplantation is an efficient treatment,and can reverse the abnormal pathology mediated by the liver in patients with WD.
• Hepatic transplantation is also indicated in the absence of liver failure in patients with neurological WD in whom chelation therapy has proved ineffective, and significant improvements in neurological features have been reported, which include the disappearance of the KF ring

FOLLOW UP [169,187]
• The frequency of monitoring of patients may vary for patients, but at a minimum should be performed twice a year.
• Repeat examination for Kayser-Fleischer rings should be performed if there is a question of patient compliance as their appearance or reappearance in a patient in whom they were absent may portend the onset of symptomatic disease.
• If patient has WD routine monitoring of serum liver biochemistries and international normalized ratio, and physical examination should be performed regularly
• Twenty-four–hour urinary excretion of copper while on medication should be measured yearly, or more frequently if there are issues of compliance or if dosage of medications is adjusted. The serum nonceruloplasmin-bound copper may be estimated in these situations
• During administration of D-penicillamine, periodic clinical, hematological, biochemical (transaminases) and routine urinary parameters are monitored weekly for 1 month, then monthly for 6 months and at 6-monthly intervals thereafter. An improvement in clinical features is usually noted after 2-3 months, continuing over a period of 1-2 years.
• If patient has wilson's disease, the same clinical and laboratory monitoring described for penicillamine also apply to trientine. The adequacy of treatment should be determined by measuring 24 hour copper excretion, which should be in the range of 200 to 500 µg (3 to 8 µmoles) daily.
• Compliance in patients taking zinc can also be checked by measuring serum zinc or 24-hour urinary zinc excretion.

SURVEILLANCE
• The incidence of cancer appeared to be related to the duration of disease. No cancers were seen in patients followed for less than ten years, compared with an incidence of 4.2 percent in those followed for 10 to 19 years, 5.3 percent for those followed for 20 to 29 years, and 15 percent for those followed for 30 to 39 years [183].
• Screen for HCC with ultrasound abdomen and alpha fetoproteins every 6 -12 months
SCREENING FAMILY MEMBERS
• First-degree relatives of patients diagnosed with Wilson's disease should be screened.
• Appropriate screening includes a history and physical examination, liver biochemical tests, complete blood count, serum ceruloplasmin, slit-lamp examination for Kayser-Fleischer rings, 24 hour basal urinary copper determination, and genotyping studies based upon the proband.
• perform the first four tests (ie, history and physical, liver biochemical tests, complete blood count and serum ceruloplasmin) and proceed with further testing only in patients with suggestive features.

PROGNOSIS [169]
• WD has a fatal outcome if not treated appropriately and in a timely manner.
• Symptomatic WD patients require lifelong treatment, because an interruption to therapy or inadequate treatment can lead to fatalities within 9 months to 3 years.
• The severity of disease at the start of treatment determines the level of disability, and an early onset is worse than a late onset in terms of prognosis.
• If treatment is begun early enough, symptomatic recovery is usually complete, leading to a normal life expectancy. Residual dysarthria and mild dystonia are relatively common in neurological WD
• A prognostic index using the Nazer score has been proposed to differentiate between fatal and nonfatal cases of WD, and is based on the severity of the abnormality of serum aspartate aminotransferase, bilirubin and prothrombin time at admission.

COUNCELLING
• Consume in moderation foods that contain high concentrations of copper (principally, shellfish, nuts, chocolate, mushrooms, and organ meets), particularly during the first year. However, dietary restriction is insufficient as sole therapy.
• It may be prudent to test drinking water obtained from wells for copper content. Municipal water supplies usually do not require analysis.
• Patients who have copper pipes in the household should be advised to flush the system before using water for cooking or consumption.
• Avoid alcohol
• Avoid hepatotoxic medication
• Discourage inter family marriages
HEMOCHROMATOSIS
DEFINITION
Hereditary hemochromatosis has been traditionally defined as an inherited disorder characterized by inappropriately high absorption of dietary iron, which leads to abnormal accumulation of iron in parenchymal organs [191,192]

DIAGNOSTIC CONSIDERATIONS
• Usually diagnosed because of elevated iron saturation or serum ferritin or a family history.
• Most patients are asymptomatic; the disease is rarely recognized clinically before the fifth decade.
• Hepatic abnormalities and cirrhosis, congestive heart failure, hypogonadism, and arthritis.
• HFE gene mutation (usually C282Y/C282Y) is found in most cases.

EPIDEMIOLOGY
• HH is most common among individuals of northern European descent, particularly of Nordic or Celtic ancestry.
• In this population, the prevalence of homozygous HH approaches 1 in 200 [193] whereas in the general US population it approaches 1 in 400 [194]
• It is less common among Africans

• Population screening has shown that the frequency of heterozygotes is about 10 percent in Caucasian populations in the United States and western Europe [195], with a frequency of about 5 per 1000 (0.5 percent) for the homozygous state [196]. The prevalence was higher (about 1 percent) in a screening study which assumed that 60 percent of patients with an elevated transferrin saturation but normal serum ferritin had early HH

Race:
• Prevalence in whites is 6 times higher than in African Americans.
• Recently, it has become prevalent in the Hispanic population. The frequency is much lower among Hispanic persons (0.27 in 1000), Asian Americans (<0.001 per 1000), Pacific Islanders (0.12 per 1000), and black persons (0.14 per 1000)
• The Celtic population is affected most frequently.
Sex:
• Men are affected more often than women, with an estimated ratio of 1.8:1.
Age:
• The disease usually becomes apparent after age 40 years in men and after age 50 years in women.
• Median age in women is 66 years.
• Median age in men is 51 years.
CAUSE [197]
• Autosomal recessive inheritance
• Mutations in the HFE gene cause increased intestinal iron absorption, perhaps via an interaction with the transferrin receptor.
• In 1996, the HFE gene was isolated on chromosome 6.