Table 1.
Hereditary severe insulin resistance syndromes.
| Gene | Clinical disorder | Inheritance | Clinical feature |
|---|---|---|---|
| INSULIN SIGNALING DEFECTS | |||
| GENERALIZED | |||
| INSR | AD/AR | Extreme hyperinsulinemia, normal lipid profile, no fatty liver, normal or elevated adiponectin, and IGFBP1 | |
| Partial | |||
| ATK2 | FPLD6 | AD | Hepatic steatosis, dyslipidemia, low adiponectin, severe insulin resistance |
| TBCID4 | AD | Postprandial insulin resistance | |
| LIPODYSTROPHIES (Congenitally absent subcutaneous fat, or partial deficiency of adipose tissue, severe dyslipidemia, fatty liver, low adiponectin/leptin) | |||
| Congenital Generalized Lipodystrophies (CGL) | |||
| AGPAT2 | CGL1 | AR | Steatosis, hypertriglyceridemia |
| BSCL2 | CGL2 | AR | Polyneuropathies and cognitive disabilities |
| CAV1 | CGL3 | AR | Short stature, pulmonary arterial hypertension |
| PTRF | CGL4 | AR | Muscular dystrophies, elevated serum CK |
| Familial Partial Lipodystrophies (FPLD) | |||
| LMNA | FPLD2 | AD | Lipoatrophy and remarkable muscular hypertrophy of limbs, gluteofemoral, and truncal region, cardiomyopathy |
| PPARG | FPLD3 | AD | Lipoatrophy limited to Limbs with centripetal obesity, hypertriglyceridemia |
| PLIN1 | FPLD4 | AD | Lipoatrophy limited to limbs and gluteofemoral region |
| CIDEC | FPLD5 | AR | Multilocular lipid droplets fat loss of lower limbs and abdomen |
| LIPE | FPLD6 | AR | Multiple symmetric lipomatosis, lipoatrophy of lower limbs |
| CAV1 | FPLD7 | AD | Early-onset cataracts |
| PCYT1A | Low adiponectin, short stature | ||
| SEVERE OBESITY (Early onset severe hyperphagic obesity, dyslipidemia, hepatic steatosis, normal/high leptin, low/normal adiponectin) | |||
| MC4R | AD/AR | Tall stature, fasting hyperinsulinemia | |
| LEP | AR | Hypogonadotropic hypogonadism, hyperphagia, immune dysfunction | |
| POMC | AR | Red hair and Adrenocorticotropic hormone (ACTH) deficiency | |
| SH2B1 | AD | Insulin resistance, Leptin resistance | |
| COMPLEX SYNDROMES (severe dyslipidemia disproportionate to total body fat mass, severe hepatic steatosis, adipose tissue failure) | |||
| RECQL2 LMNA | Werner syndrome | AR | Cataracts, immunodeficiency limb contractures, premature aging, |
| RECQL3 | Bloom syndrome | AR | Telangiectasia, short stature, increased susceptibility to cancer |
| ALMS1 | Alstrom syndrome | AR | Red-cone dystrophy, deafness, pulmonary or hepatic or renal abnormalities |
| PCNT | MOPDII | AR | Short stature, vascular anomalies |
| LMNA | MADA | AR | Neuropathies, premature aging |
| ZMPST-24 | MADB | AR | Facial and skeletal abnormalities acro-osteolysis of the distal phalanges |
| PIK3R1 | SHORT syndrome | AD/sporadic | Short stature, neurological abnormalities |
| POLD1 | MDPL syndrome | AD/sporadic | Mandibular hypoplasia, joint contractures, crowded teeth, deafness |