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Permanent neonatal diabetes mellitus(PNDM)

MedGen UID:
371484
Concept ID:
C1833104
Disease or Syndrome
Synonyms: ABCC8-Related Permanent Neonatal Diabetes Mellitus; GCK-Related Permanent Neonatal Diabetes Mellitus; INS-Related Permanent Neonatal Diabetes Mellitus; KCNJ11-Related Permanent Neonatal Diabetes Mellitus; PDX1-Related Permanent Neonatal Diabetes Mellitus; Permanent diabetes mellitus of infancy; PNDM
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
SNOMED CT: Permanent diabetes mellitus of infancy (609565001); Permanent neonatal diabetes mellitus (609565001)
 
Genes (locations): ABCC8 (11p15.1); GCK (7p13); INS (11p15.5); KCNJ11 (11p15.1); PDX1 (13q12.2)
OMIM®: 606176

Disease characteristics

Excerpted from the GeneReview: Permanent Neonatal Diabetes Mellitus
Nonsyndromic permanent neonatal diabetes mellitus (PNDM) is characterized by the onset of hyperglycemia within the first six months of life (mean age: 7 weeks; range: birth to 26 weeks) that does not resolve over time. Clinical manifestations at the time of diagnosis include intrauterine growth retardation (IUGR), hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. Therapy with insulin corrects the hyperglycemia and allows for catch-up growth. The course of PNDM varies by genotype. Pancreatic agenesis/hypoplasia caused by homozygous mutations in PDX1 results in severe insulin deficiency and exocrine pancreatic insufficiency. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Diva D De León  |  Charles A Stanley   view full author information

Additional descriptions

From OMIM
Neonatal diabetes mellitus (NDM), defined as insulin-requiring hyperglycemia within the first 3 months of life, is a rare entity, with an estimated incidence of 1 in 400,000 neonates (Shield, 2000). In about half of the neonates, diabetes is transient (see 601410) and resolves at a median age of 3 months, whereas the rest have a permanent insulin-dependent form of diabetes (PNDM). In a significant number of patients with transient neonatal diabetes mellitus, type II diabetes (see 125853) appears later in life (Arthur et al., 1997). PNDM is distinct from childhood-onset autoimmune diabetes mellitus type I (IDDM; 222100). Massa et al. (2005) noted that the diagnostic time limit for PNDM has changed over the years, ranging from onset within 30 days of birth to 3 months of age. However, as patients with the clinical phenotype caused by mutation in the KCNJ11 gene have been identified with onset up to 6 months of age, Massa et al. (2005) suggested that the term 'permanent diabetes mellitus of infancy' (PDMI) replace PNDM as a more accurate description, and include those who present up to 6 months of age. The authors suggested that the new acronym be linked to the gene product (e.g., GCK-PDMI, KCNJ11-PDMI) to avoid confusion with patients with early-onset, autoimmune type I diabetes. Colombo et al. (2008) proposed that, because individuals with INS gene mutations may present with diabetes well beyond 6 months of age and cannot be distinguished from patients with type 1 diabetes except for the absence of type 1 diabetes autoantibodies, the term PNDM should be replaced with 'monogenic diabetes of infancy (MDI),' a broad definition including any form of diabetes, permanent or transient, with onset during the first years of life and caused by a single gene defect.  http://www.omim.org/entry/606176
From GHR
Permanent neonatal diabetes mellitus is a type of diabetes that first appears within the first 6 months of life and persists throughout the lifespan. This form of diabetes is characterized by high blood sugar levels (hyperglycemia) resulting from a shortage of the hormone insulin. Insulin controls how much glucose (a type of sugar) is passed from the blood into cells for conversion to energy. Individuals with permanent neonatal diabetes mellitus experience slow growth before birth (intrauterine growth retardation). Affected infants have hyperglycemia and an excessive loss of fluids (dehydration) and are unable to gain weight and grow at the expected rate (failure to thrive). In some cases, people with permanent neonatal diabetes mellitus also have certain neurological problems, including developmental delay and recurrent seizures (epilepsy). This combination of developmental delay, epilepsy, and neonatal diabetes is called DEND syndrome. Intermediate DEND syndrome is a similar combination but with milder developmental delay and without epilepsy. A small number of individuals with permanent neonatal diabetes mellitus have an underdeveloped pancreas. Because the pancreas produces digestive enzymes as well as secreting insulin and other hormones, affected individuals experience digestive problems such as fatty stools and an inability to absorb fat-soluble vitamins.  http://ghr.nlm.nih.gov/condition/permanent-neonatal-diabetes-mellitus

Clinical features

Small for gestational age
MedGen UID:
44199
Concept ID:
C0024032
Finding
Refers to a fetus or infant who is smaller than expected for the age or gender, or who has a birth weight less than the 10th percentile.
Intrauterine growth retardation
MedGen UID:
342890
Concept ID:
C1853481
Finding
Anteverted nares
MedGen UID:
339940
Concept ID:
C1853244
Finding
Prominent metopic ridge
MedGen UID:
387953
Concept ID:
C1857949
Finding
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Downturned corners of mouth
MedGen UID:
356471
Concept ID:
C1866195
Finding
Short nose
MedGen UID:
505478
Concept ID:
CN002885
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Ptosis
MedGen UID:
504471
Concept ID:
CN000475
Finding
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Abnormality of the ear
MedGen UID:
427827
Concept ID:
CN000560
Finding
An abnormality of the ear.
Hypsarrhythmia
MedGen UID:
195766
Concept ID:
C0684276
Finding
Seizures
MedGen UID:
409523
Concept ID:
C1959629
Finding
Global developmental delay
MedGen UID:
504774
Concept ID:
CN001157
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Motor delay
MedGen UID:
504779
Concept ID:
CN001164
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Peripheral neuropathy
MedGen UID:
506330
Concept ID:
CN008687
Finding
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
Beta-cell dysfunction
MedGen UID:
370119
Concept ID:
C1969875
Finding
Diabetes mellitus
MedGen UID:
504609
Concept ID:
CN000766
Finding
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Prominent metopic ridge
MedGen UID:
387953
Concept ID:
C1857949
Finding
Limb joint contracture
MedGen UID:
369611
Concept ID:
C1969879
Finding
Radial deviation of finger
MedGen UID:
473540
Concept ID:
C2178410
Finding
Clinodactyly
MedGen UID:
807884
Concept ID:
CN220788
Finding
An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe).
Beta-cell dysfunction
MedGen UID:
370119
Concept ID:
C1969875
Finding
Hyperglycemia
MedGen UID:
5689
Concept ID:
C0020456
Disease or Syndrome
Hyperglycemia means high blood sugar or glucose. Glucose comes from the foods you eat. Insulin is a hormone that moves glucose into your cells to give them energy. Hyperglycemia happens when your body doesn't make enough insulin or can't use it the right way. People with diabetes can get hyperglycemia from not eating the right foods or not taking medicines correctly. Other problems that can raise blood sugar include infections, certain medicines, hormone imbalances, or severe illnesses.
Diabetes mellitus
MedGen UID:
504609
Concept ID:
CN000766
Finding
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Ketoacidosis
MedGen UID:
505043
Concept ID:
CN001804
Finding
Acidosis resulting from accumulation of ketone bodies.
Abnormality of the immune system
MedGen UID:
427926
Concept ID:
CN002465
Finding
An abnormality of the immune system.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
A vague complaint of debility, fatigue, or exhaustion attributable to weakness of various muscles. The weakness can be characterized as subacute or chronic, often progressive, and is a manifestation of many muscle and neuromuscular diseases. (From Wyngaarden et al., Cecil Textbook of Medicine, 19th ed, p2251)
Limb joint contracture
MedGen UID:
369611
Concept ID:
C1969879
Finding
Muscular hypotonia of the trunk
MedGen UID:
446966
Concept ID:
CN007863
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.
Limb joint contracture
MedGen UID:
369611
Concept ID:
C1969879
Finding
Radial deviation of finger
MedGen UID:
473540
Concept ID:
C2178410
Finding
Clinodactyly
MedGen UID:
807884
Concept ID:
CN220788
Finding
An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe).

Recent clinical studies

Etiology

Jahnavi S, Poovazhagi V, Kanthimathi S, Gayathri V, Mohan V, Radha V
Pediatr Diabetes 2014 Jun;15(4):313-8. Epub 2013 Oct 30 doi: 10.1111/pedi.12089. [Epub ahead of print] PMID: 24168455
Kanakatti Shankar R, Pihoker C, Dolan LM, Standiford D, Badaru A, Dabelea D, Rodriguez B, Black MH, Imperatore G, Hattersley A, Ellard S, Gilliam LK; SEARCH for Diabetes in Youth Study Group
Pediatr Diabetes 2013 May;14(3):174-80. Epub 2012 Oct 10 doi: 10.1111/pedi.12003. [Epub ahead of print] PMID: 23050777Free PMC Article
Aydin BK, Bundak R, Baş F, Maraş H, Saka N, Günöz H, Darendeliler F
J Clin Res Pediatr Endocrinol 2012 Jun;4(2):107-10. doi: 10.4274/jcrpe.524. PMID: 22672870Free PMC Article
Klupa T, Kozek E, Nowak N, Cyganek K, Gach A, Milewicz T, Czajkowski K, Tolloczko J, Mlynarski W, Malecki MT
J Clin Endocrinol Metab 2010 Aug;95(8):3599-604. Epub 2010 May 13 doi: 10.1210/jc.2010-0096. [Epub ahead of print] PMID: 20466780
Xiao X, Wang T, Li W, Song H, Gong C, Diao C, Yu M, Yuan T, Zhang Y, Sun X, Zhang Q, Lu K, Wang H, Schmitz O, Hansen T
Horm Metab Res 2009 Jul;41(7):580-2. Epub 2009 Feb 26 doi: 10.1055/s-0029-1192020. [Epub ahead of print] PMID: 19247925

Diagnosis

Huang K, Liang L, Fu JF, Dong GP
BMC Pediatr 2014 Jul 23;14:188. doi: 10.1186/1471-2431-14-188. [Epub ahead of print] PMID: 25052923Free PMC Article
Abraham N, Ahamed A, Unnikrishnan AG, Kumar H, Ellard S
JOP 2014 Mar 10;15(2):198-200. PMID: 24618446
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. [Epub ahead of print] PMID: 24468099
Kanakatti Shankar R, Pihoker C, Dolan LM, Standiford D, Badaru A, Dabelea D, Rodriguez B, Black MH, Imperatore G, Hattersley A, Ellard S, Gilliam LK; SEARCH for Diabetes in Youth Study Group
Pediatr Diabetes 2013 May;14(3):174-80. Epub 2012 Oct 10 doi: 10.1111/pedi.12003. [Epub ahead of print] PMID: 23050777Free PMC Article
Habeb AM, Al-Magamsi MS, Eid IM, Ali MI, Hattersley AT, Hussain K, Ellard S
Pediatr Diabetes 2012 Sep;13(6):499-505. Epub 2011 Nov 8 doi: 10.1111/j.1399-5448.2011.00828.x. [Epub ahead of print] PMID: 22060631

Therapy

Abraham N, Ahamed A, Unnikrishnan AG, Kumar H, Ellard S
JOP 2014 Mar 10;15(2):198-200. PMID: 24618446
Doneray H, Houghton J, Tekgunduz KS, Balkir F, Caner I
J Pediatr Endocrinol Metab 2014 Mar;27(3-4):367-71. doi: 10.1515/jpem-2013-0068. PMID: 24150202
Heo JW, Kim SW, Cho EH
Diabetes Res Clin Pract 2013 Apr;100(1):e1-2. Epub 2013 Feb 21 doi: 10.1016/j.diabres.2013.01.016. [Epub ahead of print] PMID: 23434183
Kanakatti Shankar R, Pihoker C, Dolan LM, Standiford D, Badaru A, Dabelea D, Rodriguez B, Black MH, Imperatore G, Hattersley A, Ellard S, Gilliam LK; SEARCH for Diabetes in Youth Study Group
Pediatr Diabetes 2013 May;14(3):174-80. Epub 2012 Oct 10 doi: 10.1111/pedi.12003. [Epub ahead of print] PMID: 23050777Free PMC Article
Aydin BK, Bundak R, Baş F, Maraş H, Saka N, Günöz H, Darendeliler F
J Clin Res Pediatr Endocrinol 2012 Jun;4(2):107-10. doi: 10.4274/jcrpe.524. PMID: 22672870Free PMC Article

Prognosis

Abraham N, Ahamed A, Unnikrishnan AG, Kumar H, Ellard S
JOP 2014 Mar 10;15(2):198-200. PMID: 24618446
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. [Epub ahead of print] PMID: 24468099
Jahnavi S, Poovazhagi V, Kanthimathi S, Gayathri V, Mohan V, Radha V
Pediatr Diabetes 2014 Jun;15(4):313-8. Epub 2013 Oct 30 doi: 10.1111/pedi.12089. [Epub ahead of print] PMID: 24168455
Kanakatti Shankar R, Pihoker C, Dolan LM, Standiford D, Badaru A, Dabelea D, Rodriguez B, Black MH, Imperatore G, Hattersley A, Ellard S, Gilliam LK; SEARCH for Diabetes in Youth Study Group
Pediatr Diabetes 2013 May;14(3):174-80. Epub 2012 Oct 10 doi: 10.1111/pedi.12003. [Epub ahead of print] PMID: 23050777Free PMC Article
Habeb AM, Al-Magamsi MS, Eid IM, Ali MI, Hattersley AT, Hussain K, Ellard S
Pediatr Diabetes 2012 Sep;13(6):499-505. Epub 2011 Nov 8 doi: 10.1111/j.1399-5448.2011.00828.x. [Epub ahead of print] PMID: 22060631

Clinical prediction guides

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. [Epub ahead of print] PMID: 24468099
Jahnavi S, Poovazhagi V, Kanthimathi S, Gayathri V, Mohan V, Radha V
Pediatr Diabetes 2014 Jun;15(4):313-8. Epub 2013 Oct 30 doi: 10.1111/pedi.12089. [Epub ahead of print] PMID: 24168455
Klupa T, Kozek E, Nowak N, Cyganek K, Gach A, Milewicz T, Czajkowski K, Tolloczko J, Mlynarski W, Malecki MT
J Clin Endocrinol Metab 2010 Aug;95(8):3599-604. Epub 2010 May 13 doi: 10.1210/jc.2010-0096. [Epub ahead of print] PMID: 20466780
Della Manna T, Battistim C, Radonsky V, Savoldelli RD, Damiani D, Kok F, Pearson ER, Ellard S, Hattersley AT, Reis AF
Arq Bras Endocrinol Metabol 2008 Nov;52(8):1350-5. PMID: 19169493
Bappal B, Raghupathy P, de Silva V, Khusaiby SM
Arch Dis Child Fetal Neonatal Ed 1999 May;80(3):F209-12. PMID: 10212083Free PMC Article

Recent systematic reviews

Dorchy H, Ooms H, Loeb H
Z Kinderheilkd 1975;118(4):271-81. PMID: 1130120

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