Cystic fibrosis presenting as metabolic alkalosis in a boy with the rare D579G mutation

Abstract

We report on a 10-month-old boy with hypotonic dehydration and metabolic alkalosis. Sweat test was borderline and genetic analysis was negative for common mutations. Analysis of the whole coding regions of the CFTR gene revealed the rare mutation D579G in homozygosity.

Genotype–phenotype correlation and functional studies in patients with cystic fibrosis bearing CFTR complex alleles

“…The high SCL observed in all these cases may depend on the strong functional effect that the p.Leu997Phe specifically exerts on the Cl − conductance in sweat cells observed in vitro . 21 We found a discordance between SCL and the clinical expression of the disease also in patients with other genotypes, that is, the SCL of 118 mmol/L found in a patient compound heterozygous for the p.[Arg74Trp;Val201Met;Asp1270Asn] and the p.Asp579Gly mild mutation,42 again with a mild phenotype (CBAVD alone) and a residual gating activity not matching with the diagnosis of CF (ie, 19.1%). Finally, we found several patients with a clear clinical picture of CFTR-RD, a residual CFTR gating activity on NEC around 20% and SCL ranging 30–40 mmol/L that most authors report as normal values in adults26 even if the European recommendations for CFTR-RD diagnosis suggest that SCL between 30 and 40 mmol/L would be considered borderline 2.…”

“…We found this mutation in trans with a class I–II mutation, resulting either in CF-PS (four patients) or in CFTR-RD (two patients). In two other patients, the mutation was in trans with mutations with intrinsic residual CFTR function (ie, p.Asp579Gly and p.Asp1152His) that usually have a less severe clinical impact 42 43. They had CBAVD, and they compare with four patients previously described with the same complex allele in trans with mild mutations and CBAVD alone 16 17.…”

Mutation spectrum of Egyptian children with cystic fibrosis

“…We report here for the first time in the literature this mutation in a case of PBS. Another previously reported mutation in one patient with CF and presenting with PBS, severe dehydration and hypochloremic metabolic acidosis in 2011 were ( 3849 + 1G > A and 4382delA compound heterozygosity ) (Nahida et al 2011 ), this was in addition to M2789 + 5G and F508del described in 2013 in Jordan (Dahabreh and Najada 2013 ) and D575G mutation in southern Italy (Salvatore et al 2004 ).…”

Nucleotide binding domains of human CFTR: a structural classification of critical residues and disease-causing mutations.

“…A similar situation was observed in the CFTR heterodimer in which the side chains of D579 and D1377 form hydrogen bonds with threonine residues located on the opposite subunit (T1246 and T460, respectively, labeled D in fi g. 2). The D579G mutation has been observed in patients with pancreatic suffi ciency and a mild pulmonary phenotype [55,56]. iii) T582/T1380 (labeled W in fi g. 2).…”