Cystic Fibrosis Newborn Screening in Austria Using PAP and the Numeric Product of PAP and IRT Concentrations as Second-Tier Parameters

In Austria, newborns have been screened for cystic fibrosis (CF) by analyzing immunoreactive trypsinogen (IRT) from dried blood spots (DBS)s for nearly 20 years. Recently, pancreatitis-associated protein (PAP) analysis was introduced as a second-tier test with the aim of reducing recalls for second DBS cards while keeping sensitivity high. For 28 months, when IRT was elevated (65–130 ng/mL), PAP was measured from the first DBS (n = 198,927) with a two-step cut-off applied. For the last 12 months of the observation period (n = 85,421), an additional IRT×PAP cut-off was introduced. If PAP or IRT×PAP were above cut-off, a second card was analyzed for IRT and in case of elevated values identified as screen-positive. Above 130 ng/mL IRT in the first DBS, newborns were classified as screen-positive. IRT analysis of first DBS resulted in 1961 (1%) tests for PAP. In the first 16 months, 26 of 93 screen-positive were confirmed to have CF. Two false-negatives have been reported (sensitivity = 92.8%). Importantly, less than 30% of families compared to the previous IRT-IRT screening scheme had to be contacted causing distress. Adding IRT×PAP caused a marginally increased number of second cards and sweat tests to be requested during this period (15 and 3, respectively) compared to the initial IRT-PAP scheme. One case of confirmed CF was found due to IRT×PAP, demonstrating an increase in sensitivity. Thus, the relatively simple and economical algorithm presented here performs effectively and may be a useful model for inclusion of CF into NBS panels or modification of existing schemes.

Trichohepatoenteric Syndrome or Syndromic Diarrhea—Report of Three Members in a Family, First Report from Iran

Introduction.Intractable diarrhea of infancy (IDI) includes several types of early onset diarrhea; one of the rare etiologies is trichohepatoenteric (THE) syndrome, also known as syndromic diarrhea (SD) which was primarily described by Stankler et al. Hereby we report a family with several affected members which to our knowledge is the first case report from Iran.Report of Cases.A three-year-old boy referred with short stature, poor weight gain, and intermittent steatotic diarrhea to our center. He was born to healthy, relative parents (cousins). He did not gain any weight after four months of age and began having intermittent steatotic diarrhea, abdominal distension, and fever. He was hospitalized several times. Two other children in the family also showed somewhat similar symptoms. Two sweat tests were negative for cystic fibrosis. Workup for Celiac disease was performed several times which was negative; however, gluten-free diet was tried several times which was not effective. Workup for Hirschsprung’s disease was performed but colon was ganglionic. Evidence of liver involvement was approved by elevated liver enzymes and coarse echo of liver on sonography.Discussion.Trichoenterohepatic syndrome should be put in mind in cases of intractable diarrhea presenting in a family with several affected members. Early diagnosis would save patients from unnecessary workups.

Cystic fibrosis and celiac disease - multifaceted and similar

ABSTRACT Celiac disease and cystic fibrosis share a number of clinical manifestations. The comorbidity rate of these diseases is low: 1:200000. We present a case of a child aged 1 year and 5 months, born to a mixed-marriage parents, with concomitant cystic fibrosis and celiac disease manifesting initially with chronic diarrhea. Diagnosis of cystic fibrosis was made on the basis of changes in pulmonogram and three positive sweat tests with the malabsorption managed. Celiac disease was demonstrated through immunological tests (serological test of anti-transglutaminase antibodies of IgA class), histological tests (altered duodenal mucosa) and the therapeutic effect of a gluten-free diet. This case is the first ever reported case of a child with concomitant cystic fibrosis and celiac disease in Bulgaria. The case suggests the need for targeted screening for celiac disease in children with cystic fibrosis.