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We report a 21 years old woman, without offspring, with diabetes mellitus diagnosed at 17 years of age, without ketosis or weight loss. Her body mass index was 18 kg/m2. Her C peptide was normal (2.3 ng/ml) and diabetes mellitus type 1 autoantibodies were negative. A monogenic diabetes Maturity Onset Diabetes of the Young (MODY) was proposed. Her family study disclosed a diabetic father and a brother with altered fasting glucose levels. The University of Exeter score for MODY yielded a 75.5% probability of MODY2. In the genetic-molecular study of the glucokinase gene (MODY2), the patient had a mutation at position 1343 of exon 10, corresponding to a heterozygous substitution of guanine by adenine (1343 G >A). The same mutation was found in her father and brother. This mutation is different from those previously described in the literature. The described change determines that a glycine is replaced by aspartic at amino acid 448 of the enzyme (non-synonymous substitution). The diagnosis of MODY2 was therefore confirmed in the patient and her father. The mutation was inherited by paternal line.

We report a 21 years old woman, without offspring, with diabetes mellitus diagnosed at 17 years of age, without ketosis or weight loss. Her body mass index was 18 kg/m2. Her C peptide was normal (2.3 ng/ml) and diabetes mellitus type 1 autoantibodies were negative. A monogenic diabetes Maturity Onset Diabetes of the Young (MODY) was proposed. Her family study disclosed a diabetic father and a brother with altered fasting glucose levels. The University of Exeter score for MODY yielded a 75.5% probability of MODY2. In the genetic-molecular study of the glucokinase gene (MODY2), the patient had a mutation at position 1343 of exon 10, corresponding to a heterozygous substitution of guanine by adenine (1343 GA). The same mutation was found in her father and brother. This mutation is different from those previously described in the literature. The described change determines that a glycine is replaced by aspartic at amino acid 448 of the enzyme (non-synonymous substitution). The diagnosis of MODY2 was therefore confirmed in the patient and her father. The mutation was inherited by paternal line.

Background: Some adult, obese and diabetic patients, initiate their disease with a severe diabetic ketoacidosis without a precipitating factor and do not require insulin thereafter. These patients are classified as having a "non classical" diabetes mellitus. Aim: To study the clinical, immunological, genetic and metabolic features of patients with non classical diabetes mellitus. Patients and methods: Ten patients (9 men, aged 45±12 years old) with non classical diabetes mellitus were studied. Anti islet and anti glutamic acid decarboxylase antibodies (ICA and anti GAD), HLA DQ a arginine 52 and non aspartic s57 were measured. Insulin secretion was measured by C peptide after glucagon injection and with the minimal model of Bergman. The latter model was also used to determine insulin sensitivity. Results: Three patients were immunologically classified as type 1, since they had positive ICA or antiGAD antibodies and type 1 genetics (neutral or susceptible HLA DQ a and s). They had insulin secretion after glucagon stimulus (C peptide ranging from 2.2 to 7.5 pmol/ml), but an almost absent response to a glucose load. They were also insulin resistant (a sensitivity index ranging from 0.05 to 1.67 x 10-4 min/µU x ml). These three cases could be categorized as latent type 1. The other seven patients were ICA negative and antiGAD negative. Five had a susceptible HLA genotype for type 1 diabetes and two were neutral. All had insulin secretion after glucagon stimulation and a variable response to glucose. Six were insulin resistant (sensitivity index ranging from 0.32 to 1.29 x 10-4 min/µU x ml). One patient was insulin sensitive (sensitivity index of 3.83 x 10-4 min/µU x ml). Therefore all these patients were classified as type two diabetics with an atypical debut. Conclusions: Not all diabetics presenting with a severe diabetic ketoacidosis are type I. Among these, there are subjects with a latent type 1 diabetes or with an atypical type 2 diabetes (Rev Med Chile 2001; 129: 853-60).