| Abstrakt: |
Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder characterized by low cortisol levels despite elevated adrenocorticotropin (ACTH). Mineralocorticoid secretion is classically normal. Clinical manifestations are secondary to low cortisol levels (recurrent hypoglycemia, chronic asthenia, failure to thrive, seizures) and high levels of ACTH (cutaneous-mucosal hyperpigmentation). FGD is often caused by mutations in the ACTH melanocortin 2 receptor gene (MC2R, 18p11.21, FGD type 1) or melanocortin receptor 2 accessory protein gene (MRAP, 21q22.11, FGD type 2). But mutations have also been described in other genes: the steroidogenic acute regulatory protein (STAR, 8q11.2q13.2, FGD type 3), nicotinamide nucleotide transhydrogenase (NNT, 5p12, FGD type 4) and thioredoxin reductase 2 genes (TXNRD2, 22q11.21, FGD type 5). We report the case of a 3-year-old boy recently diagnosed with FGD type 4 due to a novel mutation in NNTgene. A homozygous variant in exon 18 of the NNTgene, NM_012343.3:c.2764C>T, p.(Arg922*), determines a stop codon and, consequently, a non-functional truncated protein or absence of protein due to the nonsense-mediated decay (NMD) mechanism. We review the recent literature on NNTmutations and clinical presentations, which are broader than suspected. This disorder can result in significant morbidity and is potentially fatal if untreated. Precise diagnosis allows correct treatment and follow-up. |
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