Exocrine pancreatic insufficiency which is not due to cystic fibrosis is
a diagnostic dilemma until attention is paid to the other systemic
findings. We present such a child where focusing on other systems helped
us reach a diagnosis. A one year one month old male child was brought to
us with onset of complaints since the first few months of life. Parents
complained of failure to thrive since birth, repeated anemia needing
transfusions to maintain his hemoglobin, extensive seborrheic dermatitis
of the scalp, radiologically confirmed pneumonia at four months needing
hospitalization and intravenous antibiotics, BCG lymphadenitis at four
months needing two drug AKT isoniazid and rifampin, acute otitis media
at 6 months, and frequent oily stools since birth. Examination revealed
a child with a weight of 6 kg, height of 68 cm and a head circumference
of 43.5 cm. Systemic examination revealed seborrheic dermatitis on the
scalp and florid rickets. Investigations showed anemia,
thrombocytopenia, and intermittent neutropenia. The immunoglobulin
pattern and T cell and B cell distribution on flow cytometry was normal.
Bone marrow aspiration revealed low grade
myelodysplasia. Stool pancreatic elastase I was less than 15mcg/g
suggestive of severe pancreatic insufficiency. The karyotype was normal
and when the sweat chloride too came normal [10 meq/L], we were at a
dead end until a CT of the abdomen showed a classical appearance of
extensive fatty infiltration of the entire pancreas diagnostic of
Shwachmann Diamond Syndrome. He was put on pancreatic enzyme replacement
[Creon] with every meal along with lansoprazole. His height and weight
percentiles now approach 25, he been able to maintain a hemoglobin of 11
without transfusions and his stool output has considerably reduced.
Schwachmann Diamond Syndrome is an autosomal
recessive syndrome characterized by exocrine pancreatic insufficiency,
neutropenia which may be cyclical, metaphyseal dysostosis [the most
variable feature] and failure to thrive with short stature.
These children typically present in infancy with poor
growth and greasy foul smelling stools as did our child. The pancreatic
insufficiency may be transient and steatorrhea may spontaneously improve
with age. Our child may have either responded to enzyme replacement or
may be following the natural course of spontaneous improvement with
time. Recurrent pyogenic infections are common [otitis media, pneumonia,
osteomylitis, dermatitis, sepsis] and a frequent cause of death. Such
infections could be related to the cyclical neutropenia or to the
neutrophil hemotactic defects that some of these children possess.
Thrombocytopenia occurs in 70%; anemia occurs in 50% while neutropenia
occurs in virtually all patients. Severe anemia needing repeated
transfusions, as experienced by our patient, is unusual. Development of
a myelodysplastic syndrome or transformation to acute myeloid leukemia
has been reported in upto 33% and 24% patients respectively, especially
associated with monosomy 7 [1]. While our child’s bone marrow did reveal
mild MDS, subsequent follow up did not demonstrate any deterioration.
Shwachmann Diamond Syndrome is the second commonest cause of exocrine
pancreatic insufficiency after cystic fibrosis from which it is readily
differentiated by normal sweat chloride levels, lack of cystic fibrosis
gene, metaphyseal lesions and the characteristic hypodense appearance on
CT or MRI. Though a large number of invasive and non-invasive tests are
available for pancreatic insufficiency [2], fecal elastase is a standard
screening test with a sensitivity and specificity [3] of over 90%. A
detailed study of the SBDS gene is planned for this family since they
have requested for genetic counseling prior to the subsequent pregnancy.
Only occasional case reports appear from India, some of which highlight
the importance of the study of the SBDS gene located on chromosome 7q11
and its pseudogene [SBDSP] located in the vicinity of the SBDS gene [4].
Such a molecular diagnosis is critical before therapy such as stem cell
transplant is attempted as also for genetic counseling for subsequent
pregnancies.
1. Rothbaum R, Perrault J, Vlachos A. Shwachmann
Diamond Syndrome: report from an international conference. J Pediatr.
2002;141:266-70.
2. Walkowick J, Nousia Arvanitakis S, Henker J.
Indirect pancreatic function tests in children. J Pediatr Gastroenterol
Nutr. 2005;40:107-14.
3. Beharry S, Ellis L, Corey M. How useful is fecal pancreatic
elastase 1 as a marker of exocrine pancreatic disease? J Pediatr.
2002;141:84-90.