Shwachman-Diamond Syndrome: Causes, Symptoms, Treatment, and More

Schwachman-Diamond syndrome is a rare autosomal recessive pathology characterized by bone marrow dysfunction, pancreatic insufficiency, skeletal disorders, and delays in physical and neuropsychic development. The incidence of Shwachman-Diamond syndrome is 1 case per 50-76 thousand newborns. Moreover, in boys, pathology is diagnosed 1.5 times more often than in girls. Before the full clinical picture begins, the disease can be detected by molecular DNA analysis. With Shwachman-Diamond syndrome, children have a high susceptibility to infections, as well as a predisposition to a group of myelodysplastic diseases with a high risk of transformation into acute leukemia.

Causes

Schwachman-Diamond syndrome develops as a result of a mutation in the SBDS gene located on one of the regions of chromosome 7 in the 7qll zone. The disease is inherited in an autosomal recessive manner, when a mutant gene is passed on to a child from both parents. There are isolated cases of Shwachman-Diamond syndrome due to viral effects on embryonic tissues. The gene defect causes dysfunction of pancreatic cells and hypoplasia of hematopoiesis, which leads to severe hematological complications.

Forms

Depending on the degree of skeletal anomalies, pancreatic and bone marrow insufficiency, Shwachman-Diamond syndrome is classified into mild and severe. In the first case, the syndrome proceeds with mild manifestations that are not fully present. Patients, subject to quality therapy, live up to 18-20 years. With a severe form of Shwachman-Diamond syndrome, symptoms begin from birth and progress rapidly. In such cases, children die at an early age.

Symptoms

The first clinical signs in infants with Shwachman-Diamond syndrome appear by the age of five to six months. Against the background of insufficient secretory function of the pancreas, appetite and body weight decrease, flatulence appears in combination with constipation, diarrhea, abdominal pain, dyspepsia. In infants, from the first days of life, hemorrhagic syndrome (blood clotting disorder), thrombocytopenia, anemia and neutropenia (a decrease in the number of platelets, erythrocytes and neutrophils) develop. Hepatomegaly and steatorrhea also occur, in which an excessive amount of fat is released per day with feces.

Endocrine disorders in older children are manifested by short stature (subnanism), delayed sexual development. Bone dysplasia causes frequent fractures. In addition, underdevelopment of the bone marrow in Schwachman-Diamond syndrome contributes to the occurrence of frequent infectious diseases. Also, pathology is often accompanied by mental retardation, behavioral disorders, the appearance of age spots, anomalies of the fingers and strabismus.

Diagnostics

The initial stage of a comprehensive examination for suspected Shwachman-Diamond syndrome includes: studying a family history for genetic defects in close relatives, analyzing complaints and patient history, physical examination (palpation of the abdomen, measuring blood pressure, heart rate, etc.). For the final delivery of the diagnosis, a number of laboratory and instrumental diagnostic methods are used:

• a detailed clinical blood test to determine the level of all blood cells, as well as the concentration of enzymes and the state of fat, protein, carbohydrate metabolism.
• urine test;
• lipidogram – analysis of feces for pancreatic elastase;
• hormonal research;
• DNA diagnostics to detect mutations in the SBDS gene;
• ultrasound, CT and MRI of the abdominal organs;
• X-ray of the skeletal system, which determines the level of skeletal deformation.

In the process of diagnosis, the Schwachman-Diamond syndrome is differentiated from various diseases of the digestive system, cystic fibrosis, metaphyseal chondrodysplasia, Pearson’s syndrome, congenital dyskeratosis, etc. During the diagnostic course, patients need consultation and examination of a geneticist, gastroenterologist, neurologist and ophthalmologist.

Treatment

Therapeutic tactics are based on the results of the examination, doctors take into account the form of the Shwachman-Diamond syndrome, the age and condition of the patient. The main goal of treatment is to eliminate symptoms and maintain vital body functions for as long as possible. The lack of pancreatic enzymes is replenished with the help of replacement therapy using pancreatin preparations. All patients with Schwachman-Diamond syndrome should eat a strict, high-protein, high-fat, high-calorie diet.

When infections occur, antibacterial and antiviral agents are prescribed. According to clinical indications, probiotics and hepatoprotectors are used. Also, children and adolescents with Shwachman-Diamond syndrome often require platelet transfusions. Bone and orthopedic deformities are corrected surgically. In the case of a severe form of the disease and serious hematological disorders, such as cytopenia, myelodysplastic syndrome and leukemia, doctors prescribe bone marrow transplantation, as well as chemotherapy and radiotherapy.

Possible complications and prognosis

Currently, due to the lack of effective methods, Schwachman-Diamond syndrome is considered incurable. Shwachman-Diamond syndrome is often complicated by recurrent infectious diseases, skin abscesses, chest curvature, a significant decrease in immunity, fatty hepatosis, and liver cirrhosis. In rare cases, there is a decrease in secretory pancreatic insufficiency, and the patient’s condition improves. In this case, hematological disorders cannot be restored. Timely diagnosis and a comprehensive treatment approach allow minimizing the risk of complications and improve the quality of life. The prognosis of Shwachman-Diamond syndrome is disappointing, most children die before the age of 10. In rare cases, doctors manage to extend the survival rate to 20 years.