To the Editor: Neonatal diabetes mellitus (NDM) is a rare, monogenic form of diabetes currently defined as insulinrequiring hyperglycaemia within the first 3 months of life [1]. Neonatal diabetes can be either permanent (PNDM), requiring life-long insulin treatment, or transient (TNDM), the latter usually subsiding within 12 months of onset. In some patients with TNDM a relapse of diabetes can occur during adolescence. Recently, activating mutations of KCNJ11 (previously known as KIR6. 2), encoded by the KCNJ11 gene, have been found to result in the permanent form of this condition [2]. In addition, KCNJ11 mutations with a milder effect can also give rise to remitting, relapsing, or transient neonatal diabetes [3]. In this study, the genetic basis of a case of neonatal diabetes with an atypical clinical course was investigated. The proband (referred to as nd-BA/2) is now 20 years old, and is the only child born to healthy, unrelated parents. She was delivered at term with a weight of 2,300 g (10th centile). Her random plasma glucose was found to be elevated during the 2nd day of life, with values ranging from 10.0 to 16.6 mmol/l without ketonuria. During the first 5 weeks of life the child was in good general health and showed a regular increase of body weight despite high plasma glucose levels. Fasting C-peptide was detectable (149 pmol/l, reference values: 178–680) and tests for anti-beta-cell autoantibodies were negative. Insulin therapy was not begun until the age of 37 days, when due to severe hyperglycaemia (32 mmol/l), ketonuria and a failure to thrive, a daily dose of 1.1 U kg− 1 day− 1 was administered. After stabilisation, insulin treatment was progressively reduced and stopped at the age of 29 months because of good metabolic control and episodes of hypoglycaemia. Two OGTTs performed 5 and 17 months after insulin withdrawal showed that the patient had progressed from IGT to normal glucose tolerance (Table 1). HbA1c, determined once a year during the following 4 years, was always below 7%(4.1–6.3%). An OGTT performed at the age of 7 years and 7 months showed a recurrence of diabetes (Table 1), and 6 months later insulin therapy was re-established (0.8 U kg− 1 day− 1) because of persistently high HbA1c values (11.5%). At around the same age anti-gliadin autoantibodies were detected in the absence of clinical symptoms. Coeliac disease was confirmed by biopsy and the child was put on a glutenfree diet.

In November 2004, informed consent for genetic analysis was obtained from the proband. The intronless KCNJ11 gene was amplified in three overlapping fragments (B, C and D), with a primer pair previously described for B and C fragments [4] and modified for the D fragment (D forward: 5′ ccg ctg atc atc tac cat gtc 3′; D reverse: 5′ tac cac atg gtc cgt gtg tac 3′). We identified a heterozygous R201H mutation (c. 602 G→ A) that arose de novo in the patient.