Shwachman-Diamond syndrome in a child presenting with cystic fibrosis-type symptoms and a false-positive sweat test
Authors: Smn Brown, R Buchdahl
Journal: Journal of the Royal Society of Medicine (2008)

A six-month-old Caucasian boy was referred by his general practitioner with concerns regarding poor weight gain and poor feeding. He was the second child of unrelated parents. His mother was Italian and his father English. His older brother, aged 5 years, was known to be egg allergic but well in other respects. There was no other family history of note. He was born following a normal pregnancy and there were no initial neonatal concerns. Birth weight was 3.86 kg (75th centile). He was breast-fed for the first four months, after which he was fed on standard formula. From 14 weeks of age his weight started to falter from the 75th to the 9th centile. He had only received his first immunization at two months of age due to parental concerns regarding his health. There had been no developmental concerns.

On his first review he had appeared quite irritable on feeding and the question of cow's milk protein intolerance was raised. His feed was therefore changed to a hydrolysed formula and a dietitian reviewed him. On review three weeks later he was found to be chesty and wheezy, but with no chest deformity. He was pale and thin. His stools were noted to be fatty, loose and offensive and his weight gain had not significantly improved. From his initial blood tests he was noted to have a raised alanine aminotransferase (ALT) concentration of 73 U/L (reference range 0–45 U/L) and a borderline low neutrophil count of 1.9 × 109/L (reference range 1.5–8 × 109/L). The results of other initial investigations, performed as part of a failure-to-thrive screen, were unremarkable, including immunoglobulin E (IgE), radioallergosorbent test (RAST) to cow's milk protein, thyroid function tests, urine and faecal microbiology, coeliac screen, faecal reducing substances and amino and organic acids. Abdominal ultrasound scan was also normal. Given the concerns regarding his poor weight gain, loose offensive stools and malabsorption, a sweat test and faecal elastase level were requested.

His sweat test was reported as positive (chloride 75 mmol/L). Sodium levels were not measured. Sweat volume of at least 30 μL was collected using the Macroduct sweat collection system. Faecal elastase level was significantly low (<15 IU). His chest X ray was normal. A diagnosis was made of cystic fibrosis (CF) with pancreatic insufficiency. His parents were counselled regarding the diagnosis and he was started on prophylactic amoxicillin and clavulanic acid, as well as pancreatic enzyme and vitamin supplementation. Genotyping was requested and he was referred to a tertiary centre for joint care.

Over the next weeks he started to gain weight, although not as much as would have been expected. His stools were less oily. Genotyping failed to show any CF mutations both on routine analysis and on extended testing.

His parents became increasingly concerned that the diagnosis was incorrect. Their concerns were initially raised as they felt he did not taste salty, but were compounded by the fact that a mutation was not isolated. A repeat sweat test was sent and reported as negative (chloride 5 mmol/L). A third sweat test was also negative (8 mmol/L). Repeat faecal elastase level was still <15 IU/g, confirming pancreatic insufficiency.

Following these two negative sweat tests an alternative diagnosis was sought, in particular Shwachman-Diamond syndrome (SDS). Genotyping was requested and he was found to be homozygous for 258+2T>2C, the genetic mutation for SDS. His parents were both heterozygous. A final diagnosis was therefore made of SDS and he was referred to a tertiary centre for further management.