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Letters to JMG
Major difference in aetiology and phenotypic abnormalities between transient and permanent neonatal diabetes
  1. E Marquis1,
  2. J J Robert2,
  3. C Bouvattier3,
  4. C Bellanné-Chantelot4,
  5. C Junien1,
  6. C Diatloff-Zito1
  1. 1Inserm-U383, Hôpital Necker-Enfants Malades, 149-161 rue de Sévres, 75743 Paris Cedex 15, France
  2. 2Fédération de Pédiatrie, Hôpital Necker-Enfants Malades, Université de Paris V, 149-161 rue de Sévres, 75743 Paris Cedex 15, France
  3. 3Hôpital Saint Vincent de Paul, Paris, France
  4. 4Laboratoire de Génétique Médicale, Fondation Jean Dausset CEPH, Paris, France
  1. Correspondence to:
 Dr C Diatloff-Zito, Inserm U383, Hôpital Necker-Enfants Malades, 149-161 rue de Sévres, 75743 Paris Cedex 15, France;
 diatloff{at}necker.fr

https://doi.org/10.1136/jmg.39.5.370

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    Neonatal diabetes (ND) is a rare entity with an estimated incidence of 1/400 000 births in Europe. Hyperglycaemia usually occurs in the first few days of life and patients require insulin treatment. Intrauterine growth retardation, low birth weight, and decreased adipose tissue are frequently associated. ND is permanent in some patients (permanent ND), and in other cases hyperglycaemia is transient (transient ND, OMIM 601410). Type 2 diabetes (T2D) frequently arises in adolescence or adulthood in transient ND patients.1 Chromosome 6 abnormalities are specifically associated with transient ND,2–4 with imprinting effects unmasked by uniparental disomy (UPD) of paternal chromosome 6 and duplications in 6q24.5–7 Two imprinted genes expressed from the paternal allele in various tissues, ZAC/PLAGL1 (zinc finger, apoptosis, cell cycle/pleomorphic adenoma of the salivary gland gene like 1) and HYMAI (hydatidiform mole associated and imprinted transcript), lie in the transient ND locus in 6q24.7, 8

    The genetic causes of permanent ND forms are less known. Homozygous mutation in the glucokinase gene (GK)9 and in the insulin promoter factor-1 (IPF1) gene10 may lead to permanent ND owing to complete deficiency of the GK or IPF1 gene product. Mutations of the eukaryotic translation initiation factor-2-alpha kinase 3 (EIF2AK3) gene were found to segregate with the Wolcott-Rallison syndrome (Omim 226980), a rare autosomal recessive disorder with early onset permanent diabetes mellitus and multiple epiphyseal dysplasia (spondyloepiphyseal dysplasia).11 Clinical information and a molecular genetic study of 14 patients with transient or permanent ND forms are reported. The phenotypes of ND patients from previous reports together with cases reported here provide an initial outline for further studies and molecular mechanisms.

    PATIENTS

    Fourteen patients with ND were studied. Their main clinical features are summarised in table 1. The patients were all born at term, mean birth …

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