Table 1. Clinical features of NDM patients with defined mutations.
| Patient No. (Sex) | Clinical details | Biochemical data | Molecular genetic data | Patient's current status | ||||
|---|---|---|---|---|---|---|---|---|
| Blood sugar or HBA1C at presentation | C-peptide | HBA1C after treatment | Auto-antibodies | Type | Gene | |||
| 1 (F) | • Presented on day 1 of life • Normal abdominal ultrasound • Started on insulin at 19 days of life (Glargine& Glipizide) • Sulfonylurea stopped at 5 month and insulin stopped at 1 yr. of age |
12.9 mmol/L | N/A | 5.0% (31 mmol/mol) | • Anti islet negative • Anti GAD = 22 (positive) |
Complete loss of maternal methylation at the TND differentially methylated region on chromosome 6q24 | Off medications since one year of age. Last visit was in 2009 | |
| 2 (M) | • Presented on day 1 of life • Normal abdominal ultrasound and KUB • Normal TF and cortisol • Started on NPH , changed to Glargine and Lispro, then suphonylurea at 3 months of age • Stopped treatment at 4 months of age due to good glycemic control |
16.8 mmol/L | <33 pmol/L | 5.0% (31 mmol/mol) | • Anti islet negative • Anti GAD = 35 (positive) |
Complete loss of maternal methylation at the TND differentially methylated region on chromosome 6q25 due to UPD | Off medication since 4 month of age | |
| 3 (M) | • Presented with PNDM on day 1 of life • Normal abdominal ultrasound • On insulin pump since diagnosis • Normal RF, LF , TF & CBC • Vitamin D25 =139nmol/l |
37.2 mmol/L | 4 pmol/L | 9.0% (75 mmol/mol) | Negative for antibodies | HO | GCK | Doing well, gaining weight: 6.4kg, Ht:62.2cm both are below 3rd centile |
| 4 (M) | • Presented with PNDM on day 1 of life. • Normal abdominal ultrasound • On insulin pump since 21 days of age • Normal RF, LF , TF & CBC |
>30 mmol/L | 28 pmol/L | 6.8% (51 mmol/mol) | Negative for antibodies | HO | GCK | Doing well, gaining weight, looks well, active, playing weight 10.6 kg on 10thrd centile height: 78.3 on 50th centile |
| 5 (M) | • Presented with PNDM on day 1 of life. • Normal abdominal ultrasound • On insulin pump since day 2 of life • Normal RF, LF , TF & CBC |
18 mmol/L | Not done | 8% | Negative for antibodies | HO | GCK | Doing well, thriving with normal development. |
| 6 (M) | • Presented with hyperglycemia on day 3 of life. • Normal abdominal ultrasound • On insulin pump since day 4 of life (insulin NPH and regular) • Normal RF, LF , TF & CBC |
BG 18 mmol/L | <30 pmol/L | N/A | Negative for antibodies | HO | GCK | Doing well, thriving with normal development. |
| 7 (F) | • Presented with PNDM on day 1 of life. • Normal abdominal ultrasound • On insulin pump since day 2 of life • Chronic renal impairment with profound proteinuria , normal LF & TF |
21.8 mmol/L | <30 pmol/L | 6.7% (50 mmol/mol) | Negative for antibodies | HO | GCK | Developed renal impairment and hypertension with profound proteinuria, short stature (height 133.7cm), regular normal menstruation, no retinopathies, developed Murriac syndrome |
| 8 (F) | • Presented with PNDM on day 16 of life. • Normal abdominal ultrasound • On insulin Glargine and Lisproto-date • Normal RF, LF & TF |
HbA1C 8% , BG …20 mmol/l | <30 pmol/L | 11% , 98 mmol/mol | Negative for antibodies | HO | GCK | Doing well with normal growth height 128.9 cm in 10th centile, weight 25.5 kg in 25th centile, but having difficulties in school with poor performance, difficult to have proper metabolic control as the compliance to dietary plan and insulin dose modifications is very poor |
| 9 (F) | • Presented with hyperglycemia on day 4 of life. • Normal abdominal ultrasound • On insulin pump since day 4 of life (insulin NPH and regular) • Normal RF, LF , TF & CBC presented at |
Not available | < 30 pmol/l | 13% | Negative for antibodies | HO | GCK | Doing well clinically, but has poor metabolic control as family socio-economic status is poor, has normal growth with regular menstruation, her f inal height 151 cm at 3rd centile and compatible with mid parental height; weight is 51 Kg, no retinopathies , nephropathies or peripheral neuropathies |
| 10 (F) | • Presented with severe diabetic ketoacidosis at 2 months of age • Patient was hyperventilated for 48 hours due to recurrent convulsions • Development and cognition has been affected secondary to the hypoxic insult on presentation • Started on insulin NPH at birth 2001, then changed to Glargine and Lispro in 2010, changed to Sulfonylurea since Sept 2014 (after 13 years with insulin injection, patient was successfully shifted to oral hypoglycemic agent) |
79 mmol/L | 261 pmol/L | 5.0% (31 mmol/mol) | Negative for antibodies | HR | KCNJ11 | Has developmental delay, failure to thrive, on regular medication (insulin, regular IVIG, AED, thyroxine, Cotrimoxazole, MMF), CD25 deficiency (primary immunodeficiency) on regular immunoglobulin, but no manifestation of immunodeficiency |
| 11 (F) | • Presented at 9 months of age with hyperphosphatasia, extreme osteopenia, epiphyseal dysplasia, oval-shaped vertebra with post prandial hyperglycemia | HbAIC 5.7% | Not done | 5.50% | Negative for antibodies | HO | SLC2A2 | Has skeletal dysplasia and renal tubulopathies including glycosuria& nephrocalcinosis with preserved renal function, height 98 cm at < 3rd centile, weight 15.7 kg at < 3rd centile for her age |
| 12 (M) | • Presented at day 7 of life with hyperphosphatasic rickets • Dysplasia ,with post prandial hyperglycemia |
HbA1C 5.4% | Not done | 5.40% | Negative for antibodies | HO | SLC2A2 | Has skeletal dysplasia and renal tubulopathies including glycosuria&nephrocalcinosis with preserved renal function, height 99.8 cm on 3rd centile ,weight 13.5 kg on 10th centile for age. |
| 13 (F) | • Presented at day 14 of life with hyperphosphatasia • ALP was high since birth • Normal Calcium, normal PTH (Parathyroid hormone) |
N/A | N/A | 5.8% (40 mmol/mol) | N/A | HO | SLC2A2 | Lost to follow-up |
| 14 (M) | • Presented at day 3 of life with irritability and hyperglycemia • Has global developmental delay and multiple disease phenotypes • Neonatal diabetes on insulin pump • Autoimmune thyroid disease on thyroxine • Seizure disorder on antiepileptic medications • Had refractory pulmonary hemorrhage. |
28 mmol/L | <3 pmol/L | 5.2% (33 mmol/mol) | • Anti-GAD positive • Anti-islet positive • Anti-GBM positive • Anti-ANCA-MPO positive • Anti-PR3 positive |
HO | IL2RA | Has developmental delay, failure to thrive, on regular medication (Insulin, regular IVIG, AED, thyroxine, Cotrimoxazole, MMF), CD25 deficiency (primary immunodeficiency) on regular immunoglobulin, but no manifestation of immunodeficiency |
| 15 (M) | • Presented at age 7 months with hyperglycemia and hypothyroidism with positive thyroid peroxidase titer • At the age of one year developed thrombocytopenia and then developed interstitial pneumonia • Developed hepatosplenomegaly and generalized lymphadenopathy with no evidence of malignancy • Low immunoglobins |
High | Low | 9% (75 mmol/mol) | • Anti-GAD positive • Anti-islet positive |
HO | LRBA | Clinically sick with immunodeficiency and hypothyroidism, on methylprednisolone pulses to control his autoimmunity |
Abbreviations: RF – Renal Function, LF – Liver Function , TF – Thyroid Function & CBC – Complete Blood Count, GAD - Glutamic Acid Decarboxylase, GBM – Glomerular Basement membrane, ANCA - Anti-neutrophil Cytoplasmic Antibodies, N/A-Not Available