Heterozygous Insulin Receptor (INSR) Mutation Associated with Neonatal Hyperinsulinemic Hypoglycaemia and Familial Diabetes Mellitus: Case Series

Mutations in the insulin receptor (INSR) gene are associated with insulin resistance and hyperglycaemia. Various autosomal dominant heterozygous INSR mutations leading to hyperinsulinemic hypoglycaemia (HH) have been described in adults and children (more than 3 years of age) but not in the neonatal period. Family 1: A small for gestational age (SGA) child born to a mother with gestational diabetes presented with persistent hypoglycaemia, was diagnosed with HH and responded well to diazoxide treatment. Diazoxide was gradually weaned and discontinued by 8 months of age. Later, the younger sibling had a similar course of illness. On genetic analysis a heterozygous INSR missense variant p.(Met1180Lys) was found in the siblings, mother and grandfather but not in the father. Family 2: A twin preterm and SGA baby presented with persistent hypoglycaemia, which was confirmed as HH. He responded to diazoxide, which was subsequently discontinued by 10 weeks of life. Genetic analysis revealed a novel heterozygous INSR missense variant p.(Arg1119Gln) in the affected twin and the mother. Family 3: An SGA child presented with diazoxide responsive HH. Diazoxide was gradually weaned and discontinued by 9 weeks of age. Genetic analysis revealed a novel heterozygous INSR p.(Arg1191Gln) variant in the proband and her father. We report, for the first time, an association of INSR mutation with neonatal HH responsive to diazoxide therapy that resolved subsequently. Our case series emphasizes the need for genetic analysis and long-term follow up of these patients.     

The influence of hip rotation on femoral offset in plain radiographs

Background and purpose

Adequate restoration of femoral offset (FO) is critical for successful outcome after hip arthroplasty or fixation of hip fracture. Previous studies have identified that hip rotation influences the projected femoral offset (FO_P) on plain anteroposterior (AP) radiographs, but the precise effect of rotation is unknown.

Patients and methods

We developed a novel method of assessing rotation-corrected femoral offset (FO_RC), tested its clinical application in 222 AP hip radiographs following proximal femoral nailing, and validated it in 25 cases with corresponding computed tomography (CT) scans.

Results

The mean FO_RC was 57 (29–93) mm, which differed significantly (p < 0.001) from the mean FO_P 49 (22–65) mm and from the mean femoral offset determined by the standard method: 49 (23–66) mm. FO_RC correlated closely with femoral offset assessed by CT (FO_CT); the Spearman correlation coefficient was 0.94 (95% CI: 0.88–0.97). The intraclass correlation coefficient for the assessment of FO_RC by AP hip radiographs correlating the repeated measurements of 1 observer and of 2 independent blinded observers was 1.0 and 1.0, respectively.

Interpretation

Hip rotation affects the FO_P on plain AP radiographs of the hip in a predictable way and should be adequately accounted for.Meticulous reconstruction of the static and dynamic components of the biomechanical properties of the joint is important (Girard et al. 2006). Previous reports have emphasized the importance of restoring the femoral offset (FO) to achieve optimal postoperative joint function (Bourne and Rorabeck 2002). Furthermore, restoration of femoral offset plays a vital role in ensuring a good clinical outcome after fixation of proximal femoral fractures (Eijer et al. 2001, Paul et al. 2012). Adequate preoperative planning and precise postoperative assessment of femoral offset depend on the availability of highly standardized radiographic images of the hip joint (Merle et al. 2012). Inadequate hip rotation (HR) has been reported to result in substantial misinterpretation of the femoral offset on plain anteroposterior (AP) radiographs of the hip (Meyer and Kotecha 2008). However, the exact relationship between hip rotation and the projected femoral offset (FO_P) is not known.

List of abbreviations

AP

anteroposterior

CCD

caput-collum-diaphyseal angle

CCD_I

caput-collum-diaphyseal angle of the implant

CCD_P

projected caput-collum-diaphyseal angle

CF

calibration factor

CI

confidence interval

CN

center of femoral nail

CT

computed tomography

FH

femoral head

FO

femoral offset

FO_cos

cosine-function-dependent femoral offset

FO_CT

computed tomography-assessed femoral offset

FO_LS

lag screw-corrected femoral offset

FO_P

projected femoral offset

FO_RC

rotation-corrected femoral offset

HR

hip rotation

ICC

intraclass correlation coefficient

LS

lag screw

LS_P

projected lag screw

ND

nail diameter

ND_P

projected nail diameter

RCF

rotation-correction factor as assessed by the tangent function

RCF_cos

rotation-correction factor as assessed by the cosine function

γP

projected gamma angle of the implant

γI

gamma angle of the implant

We built a mathematical model to explain correlation between hip rotation and the FO_P on plain AP hip radiographs. A new method for assessment of rotation-corrected femoral offset (FO_RC) after proximal femoral nailing was developed and validated using computed tomography (CT) scans.     

Ameliorative effects of standardized extract from Trigonella foenum-graecum L. seeds on painful peripheral neuropathy in rats

ObjectiveTo evaluate the effects of the standardized extract of fenugreek (Trigonella foenum–graecum L. Family: Leguminasae) seed (IND01) in animal models of peripheral neuropathy.MethodsIND01 was prepared from fenugreek seeds and standardized by high performance liquid chromatography to a marker compound, trigonelline. The effects of daily oral administration of IND01 (50, 100 and 200 mg/kg) were studied in rats after partial sciatic nerve ligation (PSNL) and sciatic nerve crush injury (SNCI) during 30-days period. The measurements on thermal hyperalgesia (TH), motor function test (MFT) score and motor nerve conduction velocity (MNCV) were recorded.ResultsIND01 offered sustained protection against TH and deranged MFT scores in both models from 7-day onwards. Fifteen days of daily oral administration of IND01 restored MNCV reduction in rats with SNCI but not with PSNL.ConclusionsIND01 was found to be effective in rat models of painful peripheral neuropathy.