Shwachman-Diamond Syndrome

Shwachman-Diamond Syndrome (SDS) is a rare multi-system genetic disease. The disease, first described in 1964, mostly involves pancreatic insufficiency, bone marrow failure, and skeletal abnormalities. Other organs and systems are sometimes also affected. SDS patients are generally short-statured and often are diagnosed with failure to thrive (FTT).

It is not known exactly how frequently SDS occurs. Medical researchers estimate that it affects approximately 1 in 50,000 births, but there is no scientific basis for this number. Shwachman-Diamond syndrome is genetic and is most likely an autosomal recessive condition. Males and females are affected equally.

SDS is most likely diagnosed in infancy because symptoms generally appear by the age of four to six months. Early problems include FTT, feeding problems, and recurrent infections (which present early in at least 85 percent of children). Growth soon slows and remains below normal levels; only a few SDS children show growth beyond the third percentile of standard growth charts.

SDS patients often have a decreased ability to digest food because the cells of the pancreas, in which digestive enzymes are produced, do not function properly. Those with SDS have a defective exocrine pancreas.

The pancreatic acinar cells are the cells which produce digestive enzymes. The normal pancreas has excess capacity — only 2 percent of the acinar cells need to be functional in order to produce adequate quantities of enzymes to digest food. When less than 2 percent of exocrine pancreatic capacity is functioning, the patient will produce insufficient amounts of digestive enzymes and thus cannot digest food properly.

With inadequate numbers of functioning acinar cells, people with SDS usually have pancreatic insufficiency in early childhood. After cystic fibrosis, SDS is the second most common cause of pancreatic insufficiency in childhood. Approximately 3 percent of childhood pancreatic dysfunction is attributed to SDS.

With increasing age, up to 50 percent of SDS patients have some improvement in enzyme production and can become pancreatic sufficient. However, the underlying pancreatic defect will still be present.

The symptoms of pancreatic insufficiency are bulky, foul smelling or loose stools. These symptoms indicate that the intestines are not absorbing all of the fat and nutrients from food (malabsorption). This can lead to malnutrition and vitamin deficiencies (particularly vitamins A, D, E, and K) and other nutritional deficiencies.

Pancreatic insufficiency can be treated by taking replacement enzymes with meals. Vitamin supplementation is usually also advised. In later childhood, those who show a slight improvement in enzyme production may be able to decrease or even discontinue replacement enzymes.

Diarrhea is almost always present in infancy in SDS patients. Stools contain an excessive amount of fat and are foul smelling and greasy in appearance. Improvement in stools are seen after the enzyme-replacement therapy. Most children with SDS are not underweight or malnourished after diagnosis and treatment with enzymes. After treatment with enzymes and once normal nutritional status is achieved, most children with SDS will continue to be small. Small stature is a primary feature of SDS and correction of nutritional status and enzyme therapy will not alter this.

Some children with SDS have larger than normal appetites. This is a symptom of their malabsorption. Because they are not absorbing all their food, they eat more to fill their calorie requirements. Other children are reported to eat very small amounts this is because to some degree, appetite is determined by growth. A child who is not growing as quickly will eat less food because the body is not demanding food for growth. Very rarely, significant feeding difficulties arise in this patient group that require tube feeding.

In addition to pancreatic insufficiency, SDS patients have at least one hematological abnormality as a result of their bone marrow functioning poorly. Most people with SDS (98 percent) have neutropenia. Neutropenia is a decreased level of circulating neutrophils in the bloodstream. Neutrophils are one of the body’s white blood cells — and is the white blood cell charged with fighting bacterial and fungal infections. In approximately twothirds of SDS patients, the neutropenia is intermittent (neutrophil counts may be normal between episodes of neutropenia) and in the remaining one-third, the neutropenia is constant.

People with SDS can have other hematological abnormalities: for example, 42 percent have anemia (low red cell count), 34 percent have thrombocytopenia (low platelet count) and 19 percent have pancytopenia (all cell counts low). Other serious bone marrow complications can develop. One such complication is bone marrow failure which results in a significant underproduction of all blood cells (aplastic anemia). Some SDS patients eventually develop acute myelogenous leukemia (AML) — the risk is documented to rest around 20 to 25 percent.

Bone lesions and other skeletal abnormalities occur in SDS patients. Bone lesions have been reported in 10 to 15 percent of patients. These bone abnormalities are called metaphyseal chondrodysplasia. X-ray changes are most commonly seen in the hip, femur, tibia (leg bone) and ribs. These changes can eventually become severe enough to require surgical correction.

Abnormalities in the structure of the liver and in liver function are not uncommon. Hepatomegaly (an enlarged liver) occurs in about two-thirds of SDS patients under the age of five. Serum liver enzymes are elevated in 50 to 75 percent of cases.

However, those with hepatomegaly do not necessarily have liver enzyme abnormalities. Chronic liver disease has also been reported.

There have also been occasional reports of kidney stones in people with SDS. The cause of these may result from increased concentrations of the compound oxalate (a salt found in certain foods). This is likely caused by the malabsorption; the fat in the intestines causes too much oxalate to be absorbed from food in the intestines.

Other less frequently reported conditions related to SDS include cardiac lesions, developmental and intellectual delays, behavior and eating problems, lung disease, renal tubular malfunction, abnormal pulmonary function tests, testicular fibrosis, dental problems, diabetes mellitus, and pubertal delays.

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