Most common causes of monogenic diabetes (82)
| . | Gene . | Inheritance . | Clinical features . |
|---|---|---|---|
| MODY | |||
| GCK | AD | GCK-MODY: stable, nonprogressive elevated fasting blood glucose; typically does not require treatment; microvascular complications are rare; small rise in 2-h PG level on OGTT (<54 mg/dL [3 mmol/L]) | |
| HNF1A | AD | HNF1A-MODY: progressive insulin secretory defect with presentation in adolescence or early adulthood; lowered renal threshold for glucosuria; large rise in 2-h PG level on OGTT (>90 mg/dL [5 mmol/L]); sensitive to sulfonylureas | |
| HNF4A | AD | HNF4A-MODY: progressive insulin secretory defect with presentation in adolescence or early adulthood; may have large birth weight and transient neonatal hypoglycemia; sensitive to sulfonylureas | |
| HNF1B | AD | HNF1B-MODY: developmental renal disease (typically cystic); genitourinary abnormalities; atrophy of the pancreas; hyperuricemia; gout | |
| Neonatal diabetes | |||
| KCNJ11 | AD | Permanent or transient: IUGR; possible developmental delay and seizures; responsive to sulfonylureas | |
| INS | AD | Permanent: IUGR; insulin requiring | |
| ABCC8 | AD | Transient or permanent: IUGR; rarely developmental delay; responsive to sulfonylureas | |
| 6q24 (PLAGL1, HYMA1) | AD for paternal duplications | Transient: IUGR; macroglossia; umbilical hernia; mechanisms include UPD6, paternal duplication or maternal methylation defect; may be treatable with medications other than insulin | |
| GATA6 | AD | Permanent: pancreatic hypoplasia; cardiac malformations; pancreatic exocrine insufficiency; insulin requiring | |
| EIF2AK3 | AR | Permanent: Wolcott-Rallison syndrome: epiphyseal dysplasia; pancreatic exocrine insufficiency; insulin requiring | |
| FOXP3 | X-linked | Permanent: immunodysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome: autoimmune diabetes; autoimmune thyroid disease; exfoliative dermatitis; insulin requiring |
| . | Gene . | Inheritance . | Clinical features . |
|---|---|---|---|
| MODY | |||
| GCK | AD | GCK-MODY: stable, nonprogressive elevated fasting blood glucose; typically does not require treatment; microvascular complications are rare; small rise in 2-h PG level on OGTT (<54 mg/dL [3 mmol/L]) | |
| HNF1A | AD | HNF1A-MODY: progressive insulin secretory defect with presentation in adolescence or early adulthood; lowered renal threshold for glucosuria; large rise in 2-h PG level on OGTT (>90 mg/dL [5 mmol/L]); sensitive to sulfonylureas | |
| HNF4A | AD | HNF4A-MODY: progressive insulin secretory defect with presentation in adolescence or early adulthood; may have large birth weight and transient neonatal hypoglycemia; sensitive to sulfonylureas | |
| HNF1B | AD | HNF1B-MODY: developmental renal disease (typically cystic); genitourinary abnormalities; atrophy of the pancreas; hyperuricemia; gout | |
| Neonatal diabetes | |||
| KCNJ11 | AD | Permanent or transient: IUGR; possible developmental delay and seizures; responsive to sulfonylureas | |
| INS | AD | Permanent: IUGR; insulin requiring | |
| ABCC8 | AD | Transient or permanent: IUGR; rarely developmental delay; responsive to sulfonylureas | |
| 6q24 (PLAGL1, HYMA1) | AD for paternal duplications | Transient: IUGR; macroglossia; umbilical hernia; mechanisms include UPD6, paternal duplication or maternal methylation defect; may be treatable with medications other than insulin | |
| GATA6 | AD | Permanent: pancreatic hypoplasia; cardiac malformations; pancreatic exocrine insufficiency; insulin requiring | |
| EIF2AK3 | AR | Permanent: Wolcott-Rallison syndrome: epiphyseal dysplasia; pancreatic exocrine insufficiency; insulin requiring | |
| FOXP3 | X-linked | Permanent: immunodysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome: autoimmune diabetes; autoimmune thyroid disease; exfoliative dermatitis; insulin requiring |
AD, autosomal dominant; AR, autosomal recessive; IUGR, intrauterine growth restriction.