Fanconi syndrome and neonatal diabetes: phenotypic heterogeneity in patients with GLUT2 defects
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Abstract
Fanconi–Bickel syndrome, caused by mutations in SLC2A2 encoding the glucose transporter 2 (GLUT2), is characterized by generalized proximal renal tubular dysfunction manifesting in late infancy. We describe phenotypic heterogeneity of Fanconi–Bickel syndrome in three siblings, including early and atypical presentation with transient neonatal diabetes mellitus in one. The second-born of a non-consanguineous couple, evaluated for polyuria and growth retardation, had rickets, hepatomegaly and proximal tubular dysfunction from 4 to 6 months of age. A male sibling, who expired at 4 months, also had hepatomegaly and growth retardation. The third sibling had polyuria, glucosuria and mild proteinuria on day 3 of life. Hyperglycemia was detected 2 weeks later, which required therapy with insulin for 3 months. Mild metabolic acidosis was present at 2 weeks; hypercalciuria, phosphaturia and aminoaciduria were seen at 6 months. Sanger sequencing showed a homozygous missense mutation in SLC2A2 (exon 7, c.952G > A), causing glycine to arginine substitution; both parents were heterozygous carriers. Patients with SLC2A2 mutations may present either with isolated neonatal diabetes or with hepatomegaly and the renal Fanconi syndrome. Fanconi–Bickel syndrome shows phenotypic heterogeneity and may manifest early with subtle or atypical features, mandating a high index of suspicion.
Keywords
Fanconi–Bickel syndrome Neonatal diabetes mellitus Sodium–glucose transporter 2 Renal tubular acidosis Genetic pleiotropyNotes
Compliance with ethical standards
Conflict of interest
The authors have declared that no conflict of interest exists.
Ethical statement
This article does not contain any studies with human participants or animals performed by any of the authors.
Informed consent
Informed consent was obtained from the parents of the patients included in this article.
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