Case 1
Eight months old female referred for constipation, recurrent vomiting since the age of 2 months, lack of appetite and failure to thrive since weaning in February 2014. Family history was positive for chronic pancreatitis and negative for celiac disease (CD) and CF. At admission she was malnourished, with anthropometric parameters below normal values. Blood analysis showed Hemoglobin (Hb) 8.6 g/dL, MCV 58.4 fL, AST 457 U/L, with all other routine biochemical blood parameters in the normal range. On the basis of family history, molecular analysis for PRSS1 and SPINK1 genes were performed and resulted negative. To rule out CF, we requested ST (Cl 61 mmol/L), fecal elastase (129 μg/gr feces; normal value 200–500 μg/g feces) and an extensive CFTR gene sequencing (detection rate 96%) that detected no mutations. When ST was performed the state of hydration of the patient was normal. Two days later her clinical conditions and laboratory parameters got worse, i.e., Hb 7.7 g/dL, AST 521 U/L. Thus, on the basis of vomiting, anorexia, failure to thrive, increased level of liver enzymes and unspecified anemia, CD was suspected and confirmed by laboratory tests (Anti-Transglutaminase IgA > 200 U/mL, anti-endomysium antibodies positive, anti-deaminated gliadin IgA and IgG > 240 U/mL) and esophagogastroduodenoscopy that documented total villous atrophy. Gluten-free diet was started and a prompt improvement of both clinical conditions and blood values (Hb 7,9 g/dL, AST 190 U/L) was observed, as well as the anthropometric parameters. At discharge, fecal elastase was normal (387 μg/gr feces) and ST resulted in the normal range (Cl: 22 mmol/L).
Case 2
Male patient referred at the age of 14 months for failure to thrive, metabolic alkalosis and renal insufficiency due to bilateral renal dysplasia in 2003. The child suffered from recurrent respiratory infections (chronic airway colonization by H. influentae and intermittent colonization by S. maltophilia and P. aeruginosa) and frequent vomiting episodes. Sweat test was pathological (i.e., Cl: 122 mmol/L). While, CFTR gene analysis (detection rate 96%) detected no mutations. Pancreatic status was normal (fecal elastase 413 μg/gr feces). During the follow up lasting 10 years, the patient developed bilateral sensorineural hearing loss and a small atrial septal defect was found in absence of signs and symptoms suggestive of CF. Nevertheless, ST persistently resulted > 60 mEq/L (ranging 92 to 110 mmol/L). All the ST tests were performed in a normal state of hydration. The main causes of false positive ST were ruled out. Based on clinical features, further genetical investigation detected a karyotype suggestive of Klinefelter Syndrome (KS) (47, XXY) when he was 8 years old. The sweat test normalized only several years later.
Cases 3 and 4
The patient #3 was referred at the age of 11 years old for recurrent abdominal pain and constipation in presence of a good nutritional status. Family history was positive for colorectal polyposis, colorectal adenocarcinoma and type 2 diabetes mellitus, while it was negative for CF. At the age of 10 years old he complained of recurrent abdominal pain under umbilicus. For this reason, the following analysis were performed: H2 breath test, parasitological stool examination, laboratory tests for celiac disease, antinuclear antibodies, faecal calprotectin, urinalysis and abdominal ultrasound examination; all with normal results. After few months he was admitted twice at the emergency room for worsening of symptoms; in those occasions the ultrasound abdominal study showed coprostasis and was started a treatment with a PEG (polyethylene glycol) formulation with salt (sodium bicarbonate, sodium chloride and potassium chloride). The ST was performed and showed pathological values (i.e., Cl: 65 mmol/L). No mutations were found at the molecular analysis of CFTR gene. Therefore, the therapy with PEG was suspended and after a week the ST was normal (Cl: 12 mmol/L).
The patient #4 was referred at the age of 17 years old for history of constipation from the first month of life, an episode of sub-ileus at 5 years and intermittent therapy with faecal softening and enema that reduced the symptoms. At the age of 16 years, he was hospitalized for intestinal occlusion and CT showed a rectal fecaloma and colic overextension, so he immediately started the evacuating enemas; at the end of the hospitalization he was discharged with the indication to a colonoscopy, therapy with PEG and the evaluation in a specialistic center. He came to our attention and we performed analysis for CD, fecal calprotectin, total antibodies and routines biochemistry that resulted normal; ST was pathological (Cl: 60 mmol/L). No mutations were found at the molecular analysis of CFTR gene. Therefore, the therapy with PEG was suspended and after a week the ST was normal (Cl: 12 mEq/L).