Abstract about negative sweat tests

[Guest guest]

Hi,

maybe one day those less educated docs out there will get it! We have seen many

cases here on the

list, where CF was ruled out, because of negative sweat tests.

Peace

Torsten, dad of Fiona 5wcf

Negative sweat test in hypertrypsinaemic infants with cystic fibrosis carrying

rare CFTR mutations

Rita Padoan1, , Alessandra Bassotti1, a Seia2 and Carlo Corbetta3

(1) Cystic Fibrosis Centre, A O Istituti Clinici di Perfezionamento, via

Commenda 9, 20122 Milano,

Italy

(2) Molecular Genetic Laboratory, AO Istituti Clinici di Perfezionamento,

Milano, Italy

(3) Neonatal Screening Centre, AO Istituti Clinici di Perfezionamento, Milano,

Italy

Abstract. Persistent hypertrypsinaemia in newborn screening for cystic fibrosis

(CF) recognises

subjects at high risk to be affected. Diagnosis is confirmed by a positive sweat

test and/or by the

presence of two mutations in the cystic fibrosis transmembrane regulator gene.

The aim of the

present study was to evaluate the occurrence of a negative sweat test (chloride

<60 mmol/l) during

the first months of life, in hypertrypsinaemic infants, which would lead to a

delayed diagnosis. We

reviewed clinical charts of CF patients born between January 1993 and September

1998, when the

neonatal screening programme consisted of an immunoreactive trypsinogen

(IRT)/DNA (F508del) + IRT

strategy. Laboratory and clinical data were collected for patients diagnosed

after 12 months of

life. Out of 446,492 newborns, 104 CF patients were diagnosed giving an overall

incidence of 1:4293.

Of these, six had a blood IRT level above the cut off value (99th percentile)

and a negative sweat

test in the first trimester of life. At a mean age of 3.5years, the patients

were again referred to

our CF Centre for re-evaluation in order to confirm or exclude the disorder.

Molecular analysis

identified the following genotypes: F508del/A309D, F508del/3849+10kbCT,

F508del/R117H (in two

patients), R117H/L997F, and F508del/R117L. Conclusion: infants with cystic

fibrosis bearing a

spectrum of mild cystic fibrosis transmembrane regulator gene mutations may

present as

hypertrypsinaemic newborns with a sweat chloride within the normal range.

Reference values for

normal sweat test during the first months of life should be revised. A wide

molecular genetic

analysis is recommended for newborns presenting persistent hypertrypsinaemia and

a sweat test result

>30 mmol/l in order to diagnose atypical forms of the disease.

Keywords. CFTR gene - Cystic fibrosis - Delayed diagnosis - Sweat test

Abbreviations. b-IRT blood-immunoreactive trypsinogen CF cystic fibrosis CFTR

cystic fibrosis

transmembrane regulator DGGE denaturing gradient gel electrophoresis OLA

oligonucleotide ligation

assay

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E-mail: rita.padoan@...

Phone: +39-2-57992456

Fax: +39-2-57992814