Table 2.
Previous Reports of HNF1A-Associated Neonatal Hypoglycemia or Congenital Hyperinsulinism
| Publication citation | Variant(s) reported | ClinVar variant classification (for MODY)a | Duration of hypoglycemia (or age at which diazoxide was discontinued) | Presence of macrosomia or LGA birth weight | Report of MODY within the same individual, age at diagnosis |
|---|---|---|---|---|---|
| Brusgaard et al,3Endocr Abstr 2006 (abstract only) | 1. c.476G>A, p.Arg159Gln | 1. Pathogenic | 1. 3 y | 1. Yes, 4378 g | 1. Unclear |
| Pearson et al2, PLoS Med 2007 | 1. Mutation not reported | 1. Unknown | 1. <48 h | 1. Not reported | 1. Not reported |
| Stanescu et al,4J Clin Endocrinol Metab 2012 |
1. c.94G>T, p.Glu32X 2. c.871C>T, p.Pro291Ser |
1. Pathogenic 2. Likely benign |
1. 6 y 2. 36-42 mo |
1. Yes, 93rd percentile 2. No, 7th percentile |
1. Not reported 2. Not reported |
| Snider et al,21J Clin Endocrinol Metabol 2013 | 1. c.94G>T, p.Glu32∗ (previously included in the study by Stanescu et al4, case 1) 2. c.871C>T, p.Pro291Ser (previously included in the study by Stanescu et al4, case 2) 3. c.1541A>G, p.His514Arg |
1. Pathogenic (duplicate) 2. Pathogenic (duplicate) 3. VUS vs benign |
1. Not reported 2. Not reported 3. Not reported |
1. Not reported 2. Not reported 3. Not reported |
1. Not reported 2. Not reported 3. Not reported |
| Tung et al,5Pediatr Diabetes 2018 | 1. C.94G>T, p.Glu32 (previously included in the studies by Stanescu et al4 and Snider et al21, case 1) 2. c.871C>T, p.Pro291Ser (previously included in the studies by Stanescu et al4 and Snider et al21, case 2) 3. c.872dupC, p.Pro291fs 4. c.654T>A, p.Tyr218 5. c.654T>A, p.Tyr218 6. c.872dupC, p.Pro291fs 7. c.872delC, p.Pro291fs |
1. Pathogenic (duplicate) 2. Benign 3. Pathogenic 4. Not classified 5. Not classified 6. Pathogenic 7. Pathogenic |
1. 6.8 y 2. 3.5 y 3. Continued on diazoxide at time of publication 4. 7.3 y 5. Continued on diazoxide at time of publication 6. Continued on diazoxide at time of publication 7. Continued on diazoxide at time of publication |
1. Yes, 4167g, 92nd percentile 2. No, 7th percentile 3. No, 71st percentile 4. Not reported 5. No, 44th percentile 6. No, 84th percentile 7. Yes, 97th percentile |
“At the time of analysis, the median age of the children in this cohort was 7.0 years (IQR = 2.3-13.5 years)… screening tests for diabetes [were performed] after age 10 and none of them had developed diabetes mellitus at the time of analysis.” |
| Dusatkova et al,6J Pediatric Endocrinol Metabol 2011 | 1. c.815G>A, p.Arg272His | 4. Pathogenic/likely pathogenic | 1. “At least 1 attack of symptomatic hypoglycemia in childhood” at the age of 9 y in the setting of fasting; experienced tonic-clonic convulsions repeatedly in childhood without blood glucose check but semiquantitative estimations of urine ketone bodies were positive (grades 3-4) | 1. Yes, 4750 g (+1.99 SD) | 1. Yes, age 19 y |
| Rozenkova et al,19J Clin Endocrinol Metabol 2015 | 1. p.Gly31Asp 2. p.Asn62∗ 3. p.Leu254Gln 4. p.Arg272His (previously included in the study by Dusatkova et al6) 5. p.Glu508Lys |
1. Benign 2. VUS 3. Not classified 4. Pathogenic/likely pathogenic (duplicate) 5. VUS vs likely benign |
1. Continued on diazoxide at time of publication, age of 6 y 2. Resolved in “infancy” 3. Resolved in “infancy” 4. Resolved in “childhood” 5. Continued on diazoxide at time of publication, age of 4 y |
1. No 2. Yes 3. Yes 4. Yes 5. No |
1. Not reported 2. Not reported 3. Not reported 4. Not reported 5. Not reported |
| Yau et al,7Eur J Med Genet 2020 | 1. c.-230_-101del 2. c.713G>T, p.Arg238Met |
1. Not classified 2. Not classified |
1. Continued on diazoxide at time of publication, age of “almost 6 y” 2. Continued on diazoxide at time of publication, age of 5 y |
1. No, 4065 (+1.7 SD) 2. No, 4260 g (+1.7 SD) |
1. No 2. No |
| Cromer et al, 2022 (infants) |
1. c.811C>T, p.Arg271Trp 2. c.326+1G>T 3. c.794A>G, p.Tyr265Cys |
1. Pathogenic 2. Pathogenic 3. VUS |
1. Continued on diazoxide at time of publication, age of 1 y 2. 1 mo 3. Continued on diazoxide at time of publication, age of 2 y |
1. Yes, 4380 g (>99th percentile) 2. Yes, 3900 g (>99th percentile) 3. Yes, 5810 g (>99th percentile) |
1. No 2. No 3. No |
Abbreviations: LGA = large for gestational age; MODY = maturity-onset diabetes of the young; VUS = variant of uncertain significance.
Unique reports of cases with pathogenic or likely pathogenic variants are shown in bold