Porphyria

The porphyrias are a group of inherited or acquired disorders of certain enzymes in the heme bio-synthetic pathway (also called porphyrin pathway). They manifest with either neurological complications ("acute") or skin problems ("cutaneous"), or occasionally both. The porphyrias may be classified by the primary site of the overproduction and accumulation of the porphyrins (or their chemical precursors) as hepatic porphyrias, where porphyrins are overproduced in the liver predominantly, or erythropoietic porphyrias, where the overproduction is confined to the bone marrow and the erythrocye (red blood cell) and its precursors.

The acute, or hepatic, porphyrias primarily affect the nervous system, resulting in abdominal pain, vomiting, acute neuropathy, muscle weakness, seizures, and mental disturbances, including hallucinations, depression, anxiety, and paranoia. Cardiac arrhythmias and tachycardia (high heart rate) may develop as the autonomic nervous system is affected. Pain can be severe and can, in some cases, be both acute and chronic in nature. Constipation is frequently present, as the nervous system of the gut is affected, but diarrhea can also occur.

Given the many presentations and the relatively low occurrence of porphyria, the patient may initially be suspected to have other, unrelated conditions. For instance, the polyneuropathy of acute porphyria may be mistaken for Guillain-Barré syndrome, and porphyria testing is commonly recommended in those situations.

The cutaneous, or erythropoietic, porphyrias primarily affect the skin, causing photosensitivity (photodermatitis), blisters, necrosis of the skin and gums, itching, and swelling, and increased hair growth on areas such as the forehead. Often there is no abdominal pain, distinguishing it from other porphyrias.

In some forms of porphyria, accumulated heme precursors excreted in the urine may cause various changes in color, after exposure to sunlight, to a dark reddish or dark brown color. Even a purple hue or red urine may be seen.

Often, empirical treatment is required if the diagnostic suspicion of a porphyria is high since acute attacks can be fatal. A high-carbohydrate diet is typically recommended; in severe attacks, a glucose 10% infusion is commenced, which may aid in recovery. Pain is severe, frequently out of proportion to physical signs and often requires the use of opiates to reduce it to tolerable levels. Pain should be treated as early as medically possible, due to its severity. Nausea can be severe; it may respond to phenothiazine drugs but is sometimes intractable. Hot water baths/showers may lessen nausea temporarily, though caution should be used to avoid burns or falls. Some liver diseases may cause porphyria even in the absence of genetic predisposition. These include hemochromatosis and hepatitis C. Treatment of iron overload may be required.

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Wilson's Disease

The Wilson disease bears the name of the physician Samuel Alexander Kinnier Wilson (1878–1937, photo), a neurologist who has described the condition, including the pathological changes in the brain and liver, in 1912.

Wilson's disease or hepatolenticular degeneration is an autosomal recessive genetic disorder in which copper accumulates in tissues; this is manifested as neurological or psychiatric symptoms and liver disease that affects about 1 in 30,000 people. It is treated with medication that reduces copper absorption or removes the excess copper from the body, but occasionally a liver transplant is required. In Wilson disease, copper builds up in the liver, brain, eyes, and other organs. Over time, high copper levels can cause life-threatening organ damage.

People who get Wilson disease inherit two abnormal copies of the ATP7B gene, one from each parent. Wilson disease carriers, who have only one copy of the abnormal gene, do not have symptoms. Most people with Wilson disease have no known family history of the disease. A person's chances of having Wilson disease increase if one or both parents have it.

Kayser-Fleischer rings result from a buildup of copper in the eyes and are the most unique sign of Wilson disease. They appear in each eye as a rusty-brown ring around the edge of the iris and in the rim of the cornea. The iris is the colored part of the eye surrounding the pupil. The cornea is the transparent outer membrane that covers the eye.

People should not eat shellfish or liver, as these foods may contain high levels of copper. Other foods high in copper—including mushrooms, nuts, and chocolate—should be avoided during initial therapy but, in most cases, may be eaten in moderation during maintenance therapy.

Wilson disease requires lifelong treatment to reduce and control the amount of copper in the body. Initial therapy includes the removal of excess copper, a reduction of copper intake, and the treatment of any liver or central nervous system damage. The drugs d-penicillamine (Cuprimine) and trientine hydrochloride (Syprine) release copper from organs into the bloodstream. Most of the copper is then filtered out by the kidneys and excreted in urine.

Liver transplantation is an effective cure for Wilson's disease, but is used only in particular scenarios because of the numerous risks and complications associated with the procedure. It is used mainly in people with fulminant liver failure who fail to respond to medical treatment, or in those with advanced chronic liver disease. Liver transplantation is avoided in severe neuropsychiatric illness, in which its benefit has not been demonstrated.

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