Faculty Collaboration Database

Intrauterine and postnatal growth failure with normal GH/IGF1 axis and insulin-resistant diabetes in a consanguineous kinship. Eur J Endocrinol 2012 Mar;166(3):521-9

Date

12/16/2011

Pubmed ID

22170795

DOI

10.1530/EJE-11-0769

Scopus ID

2-s2.0-84857941135 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

OBJECTIVE: To describe the clinical and biochemical features, and perform molecular analysis for candidate abnormalities in a novel familial syndrome of intrauterine growth retardation (IUGR), failure of an adolescent growth spurt with proportional adult short stature, minimal subluxation of the 5th metacarpal-phalangeal joint, and adult-onset insulin-resistant diabetes unrelated to obesity or other manifestations of metabolic syndrome (MS).

DESIGN: Detailed clinical history, auxological, biochemical, radiological, and molecular studies, including DNA analysis and in vitro study of the GH/IGF1 pathway.

MATERIALS AND METHODS: Ten affected adults from two generations of five related families were studied in detail, and information obtained about nine other likely affected individuals.

RESULTS: Height Z-scores ranged from -7.3 to -3.8. Unaffected parents of the older generation and frequency of confirmed and suspected instances of the syndrome in the two generations studied is consistent with autosomal recessive inheritance. Insulin resistance was uniformly present in seven subjects tested who were not taking insulin. Diabetes severity did not correlate with overweight. Subjects did not have other typical manifestations of MS such as substantial hyperlipidemia, osteoporosis, or hypertension. No biochemical abnormality in the GH/IGF1 axis or molecular defect was found.

CONCLUSIONS: While the association of IUGR and adult MS, including diabetes, has been well documented, these subjects did not have typical manifestations of MS. Abnormalities in common components that could result in a combination of IUGR, severe postnatal growth, and insulin resistance have been ruled out. A mutation in an unidentified gene may affect intrauterine and postnatal growth, with insulin resistance directly affected or as a result of this growth phenomenon.

Author List

Guevara-Aguirre J, Guevara-Aguirre M, Hwa V, Prócel P, Saavedra J, Ostrer H, Fang P, Rosenfeld RG, Kerns S, Rosenbloom AL

Author

Sarah L. Kerns PhD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Cells, Cultured
Consanguinity
Diabetes Mellitus, Type 1
Female
Fetal Growth Retardation
Fibroblasts
Growth Disorders
Human Growth Hormone
Humans
Insulin Resistance
Insulin-Like Growth Factor I
Male
Middle Aged
Pedigree