| Some Stuff |
|
| Some MORE Stuff |
|
|
| Wilson's disease |
An inherited metabolic disorder characterized by excessive amounts of copper in the liver, brain, kidneys, and corneas. It can lead to tissue necrosis and fibrosis, which in turn can cause hepatic disease and neurologic changes. Without treatment, it leads to fatal hepatic failure.
CAUSES:
•genetic
TREATMENT
•avoid copper-rich foods
•penicillamine, potassium sulfide, pyridoxine, zinc acetate as alternative to penicillamine
SYNONYMS:
•progressive lenticular degeneration
•Westphal-Struempell pseudosclerosis |
|
|
|
| Wiskott-Aldrich syndrome |
Males affected by this rare x-linked genetic disorder display combined immunodeficiency, microcytic thrombocytosis and eczema leading to life threatening infections and bleeding complications. Average life span is 11 years. The syndrome has variable expression. XLT is a related but milder form with mostly platelet defects.
SIGNS AND SYMPTOMS:
•Neonatal:
•Excessive bleeding from circumcision
•Bloody diarrhea
•Petechiae and purpura
•Childhood:
•Eczema with secondary skin infections
•Recurrent bacterial infections
•Viral infections
•Hepatosplenomegaly
•Autoimmune vasculitis and hemolytic anemia
CAUSES:
•Hematopoietic cells express WASP
•Defective WASP fails to organize membrane activation
•Membranes don't form normal actin cytoskeletons
•Altered motility and inability to change cell shapes inhibits normal functions
•Platelets are intrinsically abnormal
•Accelerated destruction, sequestered in spleen
•T cells show decreased responsiveness to antigens
•B cells show abnormal antibody production
RISK FACTORS:
•Family history of WAS
•History of congenital defects
LABORATORY:
•Platelets abnormal at birth
•<30,000, MPV 2/3 normal
•B cell and T cell changes over time
•WBC count fall by age 6
•Low IgM, Normal IgG, High IgA and IgE
•Decreased response to capsular antigens
•Low CD 8 counts in 61%
•Decreased delayed hypersensitivity responses
•Decreased mitogenic responses
Drugs that may alter lab results: Antibiotics
Disorders that may alter lab results: Infections
PATHOLOGICAL FINDINGS:
•Hyperplasia of lymphoreticular system
•Vasculitic changes with multiple thromboses of small arterioles of kidney, lung, pancreas, brain
SPECIAL TESTS:
•Genetic testing for WASP
•Carrier identification
DIAGNOSTIC PROCEDURES:
Bone marrow aspiration to exclude leukemia and aplastic conditions and to HLA type for bone marrow transplantation.
TREATMENT
APPROPRIATE HEALTH CARE:
•Inpatient for acute infections
•No live virus vaccination
GENERAL MEASURES:
•HLA typed bone marrow transplant restores all abnormalities with an 85% cure rate
•Crossmatched platelets
•Irradiated, CMV negative blood products
•Aggressive antibiotic therapy for infections
•Prophylactic antibiotics
SURGICAL MEASURES:
•Splenectomy can transiently improve TCP but increases the risk of infection
ACTIVITY:
•Plan activities to help normal development
•Avoid contact sports and prevent head injuries
•Avoid crowds
PATIENT EDUCATION:
•Patient/parent counseling to cope with disease and outcome
•Genetic testing and counseling for family
MEDICATIONS
DRUG(S) OF CHOICE:
•Immunoglobulin infusions
•Prophylactic penicillin after splenectomy
•Antibiotics as indicated by culture
•Topical steroids for eczema
•Parenteral steroids, vincristine or plasmapheresis for autoimmune complications
Contraindications: Refer to manufacturer's literature
Precautions: Corticosteroids in immunosuppressed patients. Refer to manufacturer's literature
Significant possible interactions: Refer to manufacturer's literature
FOLLOW UP
PATIENT MONITORING:
As needed for therapy, monitor for infections, for progression of disease, complications
PREVENTION/AVOIDANCE:
•Genetics counseling
•Identify carriers
•Prenatal diagnosis
POSSIBLE COMPLICATIONS:
•Severe infections especially after splenectomy
•Hemorrhage, cerebral common
•Malignancies (lymphoreticular, leukemia, Kaposi's)
•Nephropathy
•Autoimmune disease in 40% can be aggressive
•Malabsorption syndrome
EXPECTED COURSE AND PROGNOSIS:
•Usual course is acute and chronic infections with progressive decrease in immune status.
•Average life expectancy is 11 years with more living past twenty with bone marrow transplant. Transplant therapy can restore all abnormalities. Causes of death have been infection (50%), bleeding (27%), malignancies (12%).
AGE-RELATED FACTORS:
Pediatric:
•Onset at birth
•First year infections with encapsulated bacteria: respiratory, meningitis, sepsis
•Later infections occur with opportunistic organisms and virus
SYNONYMS:
•Aldrich syndrome
•Eczema-TCP
•Immunodeficiency-2
REFERENCES
•Ochs HD: The Wiskott-Aldrich Syndrome. Seminars In Hematology 1998;35(4):332-45
•Brickell PM, Katz DR, Thrasher AJ: Wiskott-Aldrich syndrome: current research concepts. British J of Haematol 1998;101(4): 603-08
•Mamlok RJ: Primary immunodeficiency disorders. Allergy and Immunology 1998;25(4):739-58.
•Kuska B: Wiskott-Aldrich syndrome is a 'wonderful mystery'. J National Cancer Institute 1996;88(18):1258-61
•Litzman J, Jones A, Hann I, Chaper H, Strobel S, Morgan G: Intravenous immunoglobulin, splenectomy, and antibiotic prophylaxis in Wiskott-Aldrich syndrome. Archives of Dis in Childhood 1996;75(5):436-39 |
|
|
|
|
|
