APKD

Signs, Complications, Accelerators

11 B's:

· Signs:

Bloody urine

Bilateral pain [vs. stones, which are usually unilateral pain

Blood pressure up

Bigger kidneys

Bumps palpable

· Complications:

Berry aneurysm

Biliary cysts

Bicuspid valve [prolapse and other problems]

· Accelerators:

Boys

Blacks

Blood pressure high

Wiskott-Aldrich Syndrome

Definition

Wiskott-Aldrich syndrome (WAS) is a rare inherited disorder marked by a low level of blood platelets, eczema, recurrent infections, and a high risk of leukemia or lymph node tumors.

The syndrome is caused by a defect (mutation) in a specific gene called the WAS gene that normally codes for the protein named Wiskott - Aldrich Syndrome Protein (WASP). This vital protein is a component of cells that are important in the body’s defense against infection (lymphocytes). The same protein also functions in the cells that help prevent bleeding (platelets). A less severe form of the disease, X-linked thrombocytopenia, affects mainly the platelets.

WAS is inherited as an X-linked genetic disorder and will therefore only affect males. The gene responsible for WAS is located on the short arm of the X chromosome.

The WAS syndrome affects one in every 250,000 male children and occurs worldwide.

Signs and symptoms

Increased susceptibility to infections, eczema, and excessive bleeding are the hallmarks of WAS, although the symptoms can vary significantly from one patient to another. The immune system of patients with WAS produces too few B and T cells. Because both types of cells are affected, WAS patients are subject to repeated infections from bacteria, fungi, and viruses. Ear infections, meningitis, and pneumonia are common in boys with WAS. IgM levels are low. IgG and IgA levels may be elevated or normal.

WAS patients also have thrombocytopenia, a decreased number of platelets. The platelets may also be smaller than normal. Some of the earliest symptoms of the syndrome are hemorrhage from circumcision, bloody diarrhea, and a tendency to bruise very easily.

Anemia and an enlarged spleen (splenomegaly) are seen in some patients. About 10% of patients develop malignancies, usually leukemia or tumors in the lymph nodes (non-Hodgkin’s lymphoma).

Diagnosis

The diagnosis of WAS is usually suspected in male infants who have excessive bleeding, eczema, and frequent bacterial or viral infections. Special blood tests can then be ordered to confirm WAS. The blood of patients with Wiskott-Aldrich will show a low platelet count and a weak immune (antibody) response. It is also possible to confirm the diagnosis by obtaining a small sample of the patient’s blood and analyzing the DNA for a mutation in the WAS gene. Knowledge of the exact mutation combined with information about how much WAS protein the defective gene can produce may help predict how severe a form of the disease an individual will have.

Carrier testing

If the specific WAS gene mutation is identified in an affected child, that child’s mother can then be tested to confirm that she carries the gene.

Prenatal diagnosis

In families in which there has been one child born with WAS, prenatal testing should be offered in subsequent pregnancies. There is a 50% chance with each subsequent pregnancy that the mother, who is a carrier, will transmit the abnormal copy of the gene to her baby. The key is to first identify the particular WAS gene mutation in the child with WAS. Then, early in a pregnancy, cells can be obtained from the developing fetus by chorionic villus sampling or amniocentesis, and checked for the same mutation.

Treatment and management

Standard treatment for individuals with WAS include antibiotics for infections and platelet transfusions to limit bleeding. Immune globulin is given to strengthen the individual’s immune system. Eczema can be treated with corticosteroid creams applied directly to the skin. The spleen is sometimes removed to reduce the risk of bleeding. In individuals with WAS, however, removal of the spleen also increases the risk of infection unless antibiotics are given to prevent infections. About 50% of individuals with WAS are helped by treatment with transfer factor, which is a substance derived from the T cells of a healthy person. Transfer factor is given to improve both blood clotting and immune functions. Bone marrow transplantation has been successful in a number of cases.

It has been most successful in boys under five years of age when the donor is a sibling whose tissue type closely matches that of the individual with WAS. Attempts were also made to treat individuals with WAS with umbilical cord blood from unrelated newborns in cases when the individual diagnosed with WAS has no matched sibling donor.

Prognosis

The prognosis for males diagnosed with Wiskott – Aldrich syndrome is poor. The average individual lives about four years; those who survive into adolescence often develop cancer. Death usually occurs from severe bleeding or overwhelming infection in the first few years of life.