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Diabetes mellitus, permanent neonatal 4(PNDM4)

MedGen UID:
1711191
Concept ID:
C5394307
Disease or Syndrome
Synonyms: DIABETES MELLITUS, PERMANENT NEONATAL, 4; PNDM4
 
Gene (location): INS (11p15.5)
 
Monarch Initiative: MONDO:0030089
OMIM®: 618858

Definition

Permanent neonatal diabetes mellitus-4 (PNDM4) is characterized by chronic hyperglycemia due to severe nonautoimmune insulin deficiency diagnosed in the first months of life (summary by Polak et al., 2008). For a discussion of genetic heterogeneity of permanent neonatal diabetes mellitus, see PNDM1 (606176). [from OMIM]

Clinical features

From HPO
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Elevated hemoglobin A1c
MedGen UID:
892798
Concept ID:
C4073162
Finding
An increased concentration of hemoglobin A1c (HbA1c), which is the product of nonenzymatic attachment of a hexose molecule to the N-terminal amino acid of the hemoglobin molecule. This reaction is dependent on blood glucose concentration, and therefore reflects the mean glucose concentration over the previous 8 to 12 weeks. The HbA1c level provides a better indication of long-term glycemic control than one-time blood or urinary glucose measurements.
Diabetes mellitus type 1
MedGen UID:
41522
Concept ID:
C0011854
Disease or Syndrome
Type 1 diabetes mellitus (T1D), also designated insulin-dependent diabetes mellitus (IDDM), is a disorder of glucose homeostasis characterized by susceptibility to ketoacidosis in the absence of insulin therapy. It is a genetically heterogeneous autoimmune disease affecting about 0.3% of Caucasian populations (Todd, 1990). Genetic studies of T1D have focused on the identification of loci associated with increased susceptibility to this multifactorial phenotype. The classic phenotype of diabetes mellitus is polydipsia, polyphagia, and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Diabetic ketoacidosis
MedGen UID:
8351
Concept ID:
C0011880
Disease or Syndrome
A type of diabetic metabolic abnormality with an accumulation of ketone bodies.
Hyperglycemia
MedGen UID:
5689
Concept ID:
C0020456
Disease or Syndrome
An increased concentration of glucose in the blood.
Reduced C-peptide level
MedGen UID:
909412
Concept ID:
C4280764
Finding
A decreased concentration of C-peptide in the circulation. Since C-peptide is secreted in equimolar amounts to insulin, this feature correlates with reduced insulin secretion.

Professional guidelines

PubMed

Giouleka S, Tsakiridis I, Ralli E, Mamopoulos A, Kalogiannidis I, Athanasiadis A, Dagklis T
Obstet Gynecol Surv 2024 Apr;79(4):233-241. doi: 10.1097/OGX.0000000000001253. PMID: 38640129
Bonfanti R, Iafusco D, Rabbone I, Diedenhofen G, Bizzarri C, Patera PI, Reinstadler P, Costantino F, Calcaterra V, Iughetti L, Savastio S, Favia A, Cardella F, Lo Presti D, Girtler Y, Rabbiosi S, D'Annunzio G, Zanfardino A, Piscopo A, Casaburo F, Pintomalli L, Russo L, Grasso V, Minuto N, Mucciolo M, Novelli A, Marucci A, Piccini B, Toni S, Silvestri F, Carrera P, Rigamonti A, Frontino G, Trada M, Tinti D, Delvecchio M, Rapini N, Schiaffini R, Mammì C, Barbetti F; Diabetes Study Group of ISPED
Eur J Endocrinol 2021 Apr;184(4):575-585. doi: 10.1530/EJE-20-1030. PMID: 33606663
Denkboy Öngen Y, Eren E, Demirbaş Ö, Sobu E, Ellard S, De Franco E, Tarım Ö
J Clin Res Pediatr Endocrinol 2021 Feb 26;13(1):80-87. Epub 2020 Aug 21 doi: 10.4274/jcrpe.galenos.2020.2020.0093. PMID: 32820876Free PMC Article

Recent clinical studies

Etiology

Giouleka S, Tsakiridis I, Ralli E, Mamopoulos A, Kalogiannidis I, Athanasiadis A, Dagklis T
Obstet Gynecol Surv 2024 Apr;79(4):233-241. doi: 10.1097/OGX.0000000000001253. PMID: 38640129
GBD 2021 Nervous System Disorders Collaborators
Lancet Neurol 2024 Apr;23(4):344-381. Epub 2024 Mar 14 doi: 10.1016/S1474-4422(24)00038-3. PMID: 38493795Free PMC Article
Bonfanti R, Iafusco D, Rabbone I, Diedenhofen G, Bizzarri C, Patera PI, Reinstadler P, Costantino F, Calcaterra V, Iughetti L, Savastio S, Favia A, Cardella F, Lo Presti D, Girtler Y, Rabbiosi S, D'Annunzio G, Zanfardino A, Piscopo A, Casaburo F, Pintomalli L, Russo L, Grasso V, Minuto N, Mucciolo M, Novelli A, Marucci A, Piccini B, Toni S, Silvestri F, Carrera P, Rigamonti A, Frontino G, Trada M, Tinti D, Delvecchio M, Rapini N, Schiaffini R, Mammì C, Barbetti F; Diabetes Study Group of ISPED
Eur J Endocrinol 2021 Apr;184(4):575-585. doi: 10.1530/EJE-20-1030. PMID: 33606663
Gaál Z, Balogh I
Exp Suppl 2019;111:385-416. doi: 10.1007/978-3-030-25905-1_18. PMID: 31588541
Cordiner RLM, Pearson ER
Diabetes Obes Metab 2019 Apr;21(4):761-771. Epub 2019 Feb 11 doi: 10.1111/dom.13596. PMID: 30471177

Diagnosis

Giouleka S, Tsakiridis I, Ralli E, Mamopoulos A, Kalogiannidis I, Athanasiadis A, Dagklis T
Obstet Gynecol Surv 2024 Apr;79(4):233-241. doi: 10.1097/OGX.0000000000001253. PMID: 38640129
Bonfanti R, Iafusco D, Rabbone I, Diedenhofen G, Bizzarri C, Patera PI, Reinstadler P, Costantino F, Calcaterra V, Iughetti L, Savastio S, Favia A, Cardella F, Lo Presti D, Girtler Y, Rabbiosi S, D'Annunzio G, Zanfardino A, Piscopo A, Casaburo F, Pintomalli L, Russo L, Grasso V, Minuto N, Mucciolo M, Novelli A, Marucci A, Piccini B, Toni S, Silvestri F, Carrera P, Rigamonti A, Frontino G, Trada M, Tinti D, Delvecchio M, Rapini N, Schiaffini R, Mammì C, Barbetti F; Diabetes Study Group of ISPED
Eur J Endocrinol 2021 Apr;184(4):575-585. doi: 10.1530/EJE-20-1030. PMID: 33606663
Denkboy Öngen Y, Eren E, Demirbaş Ö, Sobu E, Ellard S, De Franco E, Tarım Ö
J Clin Res Pediatr Endocrinol 2021 Feb 26;13(1):80-87. Epub 2020 Aug 21 doi: 10.4274/jcrpe.galenos.2020.2020.0093. PMID: 32820876Free PMC Article
Iafusco D, Zanfardino A, Bonfanti R, Rabbone I, Tinto N, Iafusco F, Meola S, Gicchino MF, Ozen G, Casaburo F, Piscopo A, Miraglia Del Giudice E, Barbetti F
Minerva Pediatr 2020 Aug;72(4):240-249. Epub 2020 Apr 9 doi: 10.23736/S0026-4946.20.05838-7. PMID: 32274916
Chang WL, Huang CJ, Lei TH, Niu DM, Chiu CY, Jap TS
Diabetes Res Clin Pract 2014 Apr;104(1):e29-32. Epub 2014 Jan 8 doi: 10.1016/j.diabres.2013.12.058. PMID: 24468099

Therapy

Rey Y Formoso V, Salazar D, Ferreira S, Santos Silva R, Costa C, Castro Correia C
Endokrynol Pol 2020;71(4):363-364. Epub 2020 Jun 29 doi: 10.5603/EP.a2020.0029. PMID: 32598018
Iafusco D, Zanfardino A, Bonfanti R, Rabbone I, Tinto N, Iafusco F, Meola S, Gicchino MF, Ozen G, Casaburo F, Piscopo A, Miraglia Del Giudice E, Barbetti F
Minerva Pediatr 2020 Aug;72(4):240-249. Epub 2020 Apr 9 doi: 10.23736/S0026-4946.20.05838-7. PMID: 32274916
BIRTH-GENE (BIG) Study Working Group, Huang T, Wang T, Zheng Y, Ellervik C, Li X, Gao M, Fang Z, Chai JF, Ahluwalia TVS, Wang Y, Voortman T, Noordam R, Frazier-Wood A, Scholz M, Sonestedt E, Akiyama M, Dorajoo R, Zhou A, Kilpeläinen TO, Kleber ME, Crozier SR, Godfrey KM, Lemaitre R, Felix JF, Shi Y, Gupta P, Khor CC, Lehtimäki T, Wang CA, Tiesler CMT, Thiering E, Standl M, Rzehak P, Marouli E, He M, Lecoeur C, Corella D, Lai CQ, Moreno LA, Pitkänen N, Boreham CA, Zhang T, Saw SM, Ridker PM, Graff M, van Rooij FJA, Uitterlinden AG, Hofman A, van Heemst D, Rosendaal FR, de Mutsert R, Burkhardt R, Schulz CA, Ericson U, Kamatani Y, Yuan JM, Power C, Hansen T, Sørensen TIA, Tjønneland A, Overvad K, Delgado G, Cooper C, Djousse L, Rivadeneira F, Jameson K, Zhao W, Liu J, Lee NR, Raitakari O, Kähönen M, Viikari J, Grote V, Langhendries JP, Koletzko B, Escribano J, Verduci E, Dedoussis G, Yu C, Tham YC, Lim B, Lim SH, Froguel P, Balkau B, Fink NR, Vinding RK, Sevelsted A, Bisgaard H, Coltell O, Dallongeville J, Gottrand F, Pahkala K, Niinikoski H, Hyppönen E, Pedersen O, März W, Inskip H, Jaddoe VWV, Dennison E, Wong TY, Sabanayagam C, Tai ES, Mohlke KL, Mackey DA, Gruszfeld D, Deloukas P, Tucker KL, Fumeron F, Bønnelykke K, Rossing P, Estruch R, Ordovas JM, Arnett DK, Meirhaeghe A, Amouyel P, Cheng CY, Sim X, Teo YY, van Dam RM, Koh WP, Orho-Melander M, Loeffler M, Kubo M, Thiery J, Mook-Kanamori DO, Mozaffarian D, Psaty BM, Franco OH, Wu T, North KE, Davey Smith G, Chavarro JE, Chasman DI, Qi L
JAMA Netw Open 2019 Sep 4;2(9):e1910915. doi: 10.1001/jamanetworkopen.2019.10915. PMID: 31539074Free PMC Article
Cordiner RLM, Pearson ER
Diabetes Obes Metab 2019 Apr;21(4):761-771. Epub 2019 Feb 11 doi: 10.1111/dom.13596. PMID: 30471177
Wiley F
Diabetes Self Manag 2016 Jul-Aug;33(4):36-7. PMID: 27491106

Prognosis

Giouleka S, Tsakiridis I, Ralli E, Mamopoulos A, Kalogiannidis I, Athanasiadis A, Dagklis T
Obstet Gynecol Surv 2024 Apr;79(4):233-241. doi: 10.1097/OGX.0000000000001253. PMID: 38640129
Denkboy Öngen Y, Eren E, Demirbaş Ö, Sobu E, Ellard S, De Franco E, Tarım Ö
J Clin Res Pediatr Endocrinol 2021 Feb 26;13(1):80-87. Epub 2020 Aug 21 doi: 10.4274/jcrpe.galenos.2020.2020.0093. PMID: 32820876Free PMC Article
Gaál Z, Balogh I
Exp Suppl 2019;111:385-416. doi: 10.1007/978-3-030-25905-1_18. PMID: 31588541
Chang WL, Huang CJ, Lei TH, Niu DM, Chiu CY, Jap TS
Diabetes Res Clin Pract 2014 Apr;104(1):e29-32. Epub 2014 Jan 8 doi: 10.1016/j.diabres.2013.12.058. PMID: 24468099
Weiss MA
J Biol Chem 2009 Jul 17;284(29):19159-63. Epub 2009 Apr 24 doi: 10.1074/jbc.R109.009936. PMID: 19395706Free PMC Article

Clinical prediction guides

Denkboy Öngen Y, Eren E, Demirbaş Ö, Sobu E, Ellard S, De Franco E, Tarım Ö
J Clin Res Pediatr Endocrinol 2021 Feb 26;13(1):80-87. Epub 2020 Aug 21 doi: 10.4274/jcrpe.galenos.2020.2020.0093. PMID: 32820876Free PMC Article
Iafusco D, Zanfardino A, Bonfanti R, Rabbone I, Tinto N, Iafusco F, Meola S, Gicchino MF, Ozen G, Casaburo F, Piscopo A, Miraglia Del Giudice E, Barbetti F
Minerva Pediatr 2020 Aug;72(4):240-249. Epub 2020 Apr 9 doi: 10.23736/S0026-4946.20.05838-7. PMID: 32274916
Hashimoto Y, Dateki S, Hirose M, Satomura K, Sawada H, Mizuno H, Sugihara S, Maruyama K, Urakami T, Sugawara H, Shirai K, Yorifuji T
Pediatr Diabetes 2017 Nov;18(7):532-539. Epub 2016 Sep 29 doi: 10.1111/pedi.12447. PMID: 27681997
Chang WL, Huang CJ, Lei TH, Niu DM, Chiu CY, Jap TS
Diabetes Res Clin Pract 2014 Apr;104(1):e29-32. Epub 2014 Jan 8 doi: 10.1016/j.diabres.2013.12.058. PMID: 24468099
Weiss MA
J Biol Chem 2009 Jul 17;284(29):19159-63. Epub 2009 Apr 24 doi: 10.1074/jbc.R109.009936. PMID: 19395706Free PMC Article

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