Case Reflection of a Child With p.Phe312del/p.Phe508del Genotype Undetected on Newborn Screening and With No Clinical Features of Cystic Fibrosis Despite a Sweat Chloride Value in the Diagnostic Range

病例回顾:一名新生儿筛查未检出p.Phe312del/p.Phe508del基因型的儿童,尽管汗液氯化物值在诊断范围内,但无囊性纤维化临床表现。

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Abstract

This clinical overview reflects on a case of a nine-month-old boy presenting with mild bronchiolitis and persistently elevated transaminases. A total creatine kinase (CK) was requested to assess for dystrophinopathies, which was significantly elevated at 3000 U/L on repeat samples. Molecular testing confirmed the diagnosis of Becker's muscle dystrophy (BMD). During molecular testing, two cystic fibrosis (CF) mutations were incidentally detected, a p.Phe312del mutation and the classic CF-causing mutation p.Phe508del. Sweat chloride testing was repeatedly elevated in keeping with the diagnosis of CF. Despite the significantly elevated sweat chloride and molecular genetic profile showing heterozygosity for p.Phe508del and p.Phe312del mutations, the patient did not show any clinical manifestation of CF. During the newborn screening, immunoreactive trypsinogen (IRT) was 26 ng/mL, below the upper limit value used for screening (54 ng/mL) at that time. This case illustrates two important points: firstly, patients heterozygous for p.Phe312del and p.Phe508del mutations may not be detected during newborn screening and may not have clinical manifestations of cystic fibrosis despite having unequivocally elevated sweat chloride. Secondly, an unexplained elevation of transaminases should trigger creatine kinase testing to check for dystrophinopathies.

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