Table 1.
Approaches used to identify monogenic diabetes in pediatric populations
| Type of study | Country | Area | Initial cohort (n) | Cohort characteristics | Testing strategy (subgroup tested) | Genes tested | Prevalence in genetically tested | Minimal prevalence of monogenic diabetes | Reference |
|---|---|---|---|---|---|---|---|---|---|
| Systematic studies ordered by number in study | |||||||||
| Multi-centre population based | USA | 6 centres: California, Ohio, Hawaii, South Carolina, Washington | 5963 | 1) Diagnosed <20yrs 2) Diagnosed<6mths |
1) AB-ve (x2), fasting c-peptide ≥0.8ng/ml (n=586) 2) Diagnosed <6mths (n=7) |
1) HNF1A, HNF4A, GCK, 2) KCNJ11, INS, ABCC8 |
1) 8.4% (47/586) 2) 71.4% (5/7) |
1.2% 0.2% (Total 1.4%) |
Pihoker 2013 Shankar2013 |
| Nationwide population based | Norway | Nationwide | 2756 | Newly diagnosed aged 0-14 yrs | 1) AB-ve (x2) and affected parent (n=46) 2) AB-ve, HbA1c <7.5% (58mmol/mol) and not on insulin (n=10) 3) diagnosed <12 mths (n=24) |
1) HNF1A, HNF4A, MIDD 2)GCK, 3)KCNJ11, ABCC8, INS |
1) 13.0% (6/46) 2) 30.0% (3/10) 3) 16.6% (4/24) |
1.1% | Irgens 2013 |
| Epidemiological data / nationwide genetic test results | Poland | 3 centres: Lodz, Katowice, Gdansk | 2568 | Aged 0-18 yrs | 1) AB-ve, affected parent, non insulin dependent 2) HbA1c<7.5% (58mmol/mol) 3) Diagnosed <6mths 4) Syndromic diabetes |
1)HNF1A, HNF4A, HNF1B, 2)GCK 3)KCNJ11, ABCC8, INS, 4)WFS, Alstrom |
32.1% (100/311) | 3.1-4.2% | Fendler 2012 |
| Single pediatric clinic population | USA | New York | 939 | Clinical diagnosis T1D Aged 6mths-20yrs |
AB-ve (x3) plus either HbA1c≤7% (53mmol/mol) and ≤0.5u insulin /kg/day / > 1yr post diagnosis c-peptide+ or 3 gen. FH (n=58) | GCK HNF1A |
8.6% (5/58) | 0.5%* | Gandica 2015 |
| Pediatric clinics in single city | Australia | Sydney | 497 | 1) Clinical diagnosis T1D 2) Diagnosed 6mths – 16 yrs |
AB-ve (x4- on 2 occasions (n=19) | 1) HNF1A, HNF4A, 2) INS, KCNJ11 |
5% (1/19) | 1.2%* | Hameed 2010 |
| Single pediatric clinic population | Spain | Madrid | 252 | 1) Clinical diagnosis T1D 2) Diagnosed 6mths - 17yrs of age |
AB-ve (x5) (n=25) | 1)HNF1A, HNF4A, 2)KCNJ11, INS |
8.0% (2/25) | 0.8%* | Rubio-Cabezas 2009 |
| Pediatric clinic: Case Histories | New Zealand | South Island | 160 | Pediatric diabetes <18yrs | AB-ve ( x2?) (n=4) | GCK, HNF1B, HNF1A | 2.5% (4/160) | 2.5% | Wheeler 2013 |
| Nationwide | Japan | Centres throughout Japan | N/K | Aged 6mths -20yrs | 1) AB-ve (x 2), BMI<25, dominant family history or 2) renal cysts (n=80) |
1) HNF1A, GCK, HNF4A, MIDD, 2) HNF1B |
47.5% (38/80) | - | Yorifuji 2012 |
| Single pediatric clinic population | USA | Colorado | N/K | Diabetes <25 yrs | c-peptide ≥0.1ng/ml, AB-ve (x3) (n=97) |
HNF1A, HNF4A, GCK, PDX1, HNF1B | 22.7% (22/97) | N/K | Chambers 2015 |
| Non systematic studies relying on clinical recognition and clinical testing | |||||||||
| Type of study | Country | Area | Initial cohort of subject with diabetes and the population taken from (n) | Cohort characteristics | How monogenic diabetes was defined | Number with monogenic diagnosis (% all diabetes) | Prevalence per 100,000 population | Reference | |
| Postal questionnaire survey | UK | Nationwide | 15,255 (59M pop ) | Diabetes <16 yrs ′non T1′ | Confirmed by genetic test | 20 (0.13%) | 0.17 | Ehtisham 2004 | |
| Questionnaire and telephone survey | Germany | State of Baden-Württenberg | 2640 (2.6M) pop | 0-20yrs | Clinician diagnosis (45% genetically confirmed) | 58 (2.1%) | 2.3 | Neu 2009 | |
| Assessment of Childhood Diabetes registry | Germany | Saxony (34 paed clinics) | 865 new cases Prevalence cases not stated (4.8M pop) |
Newly diagnosed aged 0-15yrs | Confirmed by genetic test | 21 (2.4%) prevalence in incident cases | Cannot be calculated | Galler 2009 | |
| Surveillance questionnaire (Physician reporting) | Canada | National | Not stated (35M pop Canada) | Newly diagnosed non-type 1 diabetes <18yrs | Clinical diagnosis genetically confirmed in ~50% | 31 (% cannot be calculated) | 0.32 | Amed 2010# | |
| Observational investigation of database | Austria / Germany | 262 Pediatric clinics | 40,567 Population | Age <20yrs , Diagnosed <18 yrs | Clinician diagnosis MODY usually confirmed by genetic test (polymorphisms not excluded#) | 339 all cases (0.8%) 263 (0.65%) genetic positive# | Cannot be calculated | Schober 2009 | |
N/K: Not known
*
only patients with a clinical diagnosis of Type 1 diabetes were included so the prevalence is likely to be underestimated
#
subsequent study (Awa 2011 ) indicated 38% of reported HNF1A cases were polymorphisms not mutations.