Table 1 Clinical and biological features in patients with TYMP variants. The age indicated in brackets is the age at diagnosis for the corresponding symptom. Regarding fasting glucose, fasting hyperglycemia is defined by values ranging from 6.1 to 6.9 mmol/L, and diabetes by values ≥ 7 mmol/L. Regarding 2h-OGTT glucose, glucose intolerance is defined by values ranging from 7.8 to 11 mmol/L, and diabetes by values ≥ 11.1 mmol/L. The formula to calculate the insulinogenic index is the following: (insulinemia T30 min – insulinemia T0 min)/(glycemia T30 min – glycemia T0 min) [26]
| Â | Patient 1 | Patient 2 | Patient 3 |
|---|---|---|---|
General characteristics | |||
 Gender | F | M | F |
 Origin | Turkish | Turkish | Turkish |
 Age (years) | deceased at the age of 24 | 27 | 20 |
 Height (m) | 1.63 | 1.70 | 1.60 |
 Weight (kg) | 34 | 53 | 37.5 |
 Body mass index (kg/m2) | 12.8 | 18.3 | 14.6 |
 Age at first symptoms (years) | 14 | 18 | 15 |
Lipodystrophic signs | |||
 Generalized lipoatrophy | yes (14 years) | yes (18 years) | yes (13 years) |
 Muscular hypertrophy | no | yes | yes |
 % of total body fat mass - DXA | 9.6 | 8.4 | nd |
 Leptin levels (ng/mL) | 1.9 | 0.5 | 0.53 |
Gynecological features | |||
 Hirsutism | yes | na | yes |
 Amenorrhea | yes | na | yes |
Glucose homeostasis | |||
 Fasting Insulin (pmol/L) (N < 70 pmol/L) | 358.3 | 519.4 | 530.6 |
 Acanthosis nigricans | yes | yes | yes |
 Diabetes | yes (18 years) | no | yes (16 years) |
 Fasting glucose (N: 4.1-6.1 mmol/L) | 5.2 | 4.2 | 14.2 |
 2h-OGTT glucose (N: ≤ 7.8 mmol/L) | 13 | 10.9 | nd |
 Insulinogenic index (N: 80-180 pmol/mmol) | 84.3 | 110.1 | nd |
 Fasting C-peptide (N: 0.26-0.99 nmol/L) | 2.2 | 3.3 | nd |
 HbA1c (N <6%) | 5 | 4.9 | 8.4 |
 Adiponectin levels (normal values: 2-14 mg/L) | < 0.01 | 0.37 | nd |
Liver manifestations | |||
 Hepatomegaly | yes | yes | yes |
 Liver steatosis | yes | yes | yes |
 AST / ALT levels (IU/L) (N: <40 IU/L) | 142 / 52 | 100 / 134 | 50/40 |
 GGT (IU/L) (N: 8-44 IU/L) | 77 | 65 | 142 |
Dyslipidemia | |||
 Triglycerides levels (N: <1.7 mmol/L) | 7.6 | 2.2 | 28.1 |
 HDL-cholesterol (N: >1 mmol/L) | 0.77 | 0.65 | 0.33 |
Neurological signs | |||
 Clinical demyelinating sensory motor peripheral neuropathy | lower and upper limbs (20 years) | no | lower and upper limbs (16 years) |
 Electromyogram abnormalities | yes | yes | yes |
 Leukoencephalopathy | yes | no | yes |
 Ptosis | yes, unilateral | no |  |
 Muscular atrophy | yes |  |  |
Gastrointestinal signs | |||
 Gastroparesis | yes (20 years) | no | yes (16 years) |
 Abdominal pain | yes | no | yes |
 Diarrhea | no | no | yes |
Other clinical signs | |||
 Hypogammaglobulinemia | yes | no | yes |