Donohue Syndrome

Rare autosomal recessive syndrome of extreme insulin resistance due to mutations in the binding domain of INSULIN RECEPTOR. Clinical features include severe intrauterine and postnatal growth restriction, characteristic dysmorphic FACIES; HIRSUTISM; VIRILIZATION; multiple endocrine abnormalities, and early death.

Also Known As:

Networked: 164 relevant articles (2 outcomes, 8 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Insulin Resistance
2.	Hyperglycemia
3.	Congenital Generalized Lipodystrophy (Berardinelli-Seip Congenital Lipodystrophy)
4.	Donohue Syndrome
5.	Hypoglycemia (Reactive Hypoglycemia)

Experts

1.	Rabbone, Ivana: 2 articles (11/2015 - 12/2013)
2.	Barbetti, Fabrizio: 2 articles (11/2015 - 12/2013)
3.	Galderisi, Alfonso: 2 articles (11/2015 - 12/2013)
4.	Cerutti, Franco: 2 articles (11/2015 - 12/2013)
5.	Bonora, Enzo: 2 articles (12/2013 - 03/2008)
6.	Cochran, Elaine: 2 articles (11/2013 - 04/2004)
7.	Gorden, Phillip: 2 articles (11/2013 - 04/2004)
8.	Jin, Dong-Kyu: 2 articles (05/2012 - 01/2010)
9.	Semple, Robert K: 2 articles (01/2012 - 08/2007)
10.	Zoppini, Giacomo: 2 articles (01/2010 - 03/2008)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Donohue Syndrome:

1.	Insulin (Novolin)FDA Link 04/01/1983 - "Decreased insulin binding to cultured cells from a patient with the Rabson-Mendenhall syndrome: dichotomy between studies with cultured lymphocytes and cultured fibroblasts." 01/01/2015 - "Donohue syndrome and use of continuous subcutaneous insulin pump therapy." 08/01/2008 - "Rabson mendenhall syndrome is a rare autosomally recessive inherited insulin resistant disorder. " 07/01/2008 - "Missense mutations in the beta subunits are commonly associated with a milder impairment of insulin binding and milder phenotype with prolonged survival and less dysmorphism, the so called Rabson-Mendenhall syndrome. " 08/08/2003 - "Mutations in these receptors cause the inherited insulin-resistant syndrome leprechaunism. "
2.	Idiopathic hypertrophic subaortic stenosis (IHSS)IBA 08/01/2013 - "We report a patient with pronounced clinical picture of leprechaunism who developed severe progressive hypertrophic obstructive cardiomyopathy (HOCM) and renal tubular dysfunction which improved on continuous subcutaneous infusion of recombinant human insulin-like growth factor-1 (rhIGF-I). "
3.	recombinant methionyl human leptinIBA 04/01/2004 - "Efficacy of recombinant methionyl human leptin therapy for the extreme insulin resistance of the Rabson-Mendenhall syndrome."
4.	Insulin ReceptorIBA 01/01/1990 - "A pregnancy at risk for leprechaunism was examined and an unaffected child was correctly predicted by study of the functionality of the insulin receptor on cultured amniocytes and by echoscopic examination." 09/01/1989 - "Other studies with the radioimmunoassay indicated that insulin receptors were decreased both in monocytes from obese hyperinsulinemic subjects and in fibroblasts from patients with leprechaunism." 09/01/2015 - "The patient's diagnosis was based on compound heterozygous mutations in two alleles of the insulin receptor gene, thus confirming leprechaunism. " 09/01/2015 - "Mutations were looked for in the insulin receptor gene of a four-month-old female baby with leprechaunism. " 01/01/2015 - "Donohue syndrome is a rare autosomal recessive condition caused by severe loss-of-function mutations in the insulin receptor (INSR) gene. "
5.	Insulin-Like Growth Factor I (IGF-1)IBA 02/01/1998 - "In the present study, we investigated the biological actions of recombinant human insulin-like growth factor I (rhIGF-I) in fibroblasts derived from a patient with leprechaunism. " 07/01/2008 - "This is the first report of the characteristic phenotypes of the teeth and craniofacial morphology of a patient with leprechaunism treated with IGF-I. In addition, the possible association between these features and long-term IGF-I treatment is discussed." 07/01/2008 - "Dental and craniofacial characteristics in a patient with leprechaunism treated with insulin-like growth factor-I." 07/01/2005 - "A 12-year-old girl with leprechaunism has been treated with IGF-1 since she was 6 months old. " 10/01/2001 - "Decreased half-life of insulin-like growth factor I in Rabson-Mendenhall syndrome."
6.	Blood Glucose (Blood Sugar)IBA 05/01/1993 - "This study assessed the potential effectiveness of IGF-I as a blood glucose lowering agent in patients with extreme insulin resistance syndromes, including type A insulin resistance, congenital generalized lipodystrophy, and leprechaunism. "
7.	Glucose (Dextrose)FDA LinkGeneric 06/01/2002 - "Patients with the most severe syndrome, leprechaunism, have growth restriction, altered glucose homeostasis and early death (usually before 1 year of age). " 11/01/1980 - "Postprandial and postabsorptive glucose metabolism was studied in a 3-yr-old girl with leprechaunism by substrate and hormonal measurements and by quantifying hepatic glucose output during continuous infusion of D-[6-6-2H2]-glucose. " 07/01/2008 - "Leprechaunism is an autosomal recessive disease characterized by elfin-like faces, loss of glucose homeostasis, and severe insulin resistance. " 02/01/2002 - "Leprechaunism represents the most severe form of insulin resistance syndrome, manifesting abnormal glucose metabolism and intrauterine, postnatal growth retardation. " 02/01/1998 - "Leprechaunism is the most severe form of insulin resistance, manifesting with abnormal glucose metabolism and retarded growth. "
8.	Phosphotransferases (Kinase)IBA 04/01/1997 - "A homozygous kinase-defective mutation in the insulin receptor gene in a patient with leprechaunism." 08/01/1999 - "To determine the mechanism causing this progression and the paradoxical fasting hypoglycemia, we conducted a retrospective study in a patient with Rabson-Mendenhall syndrome, who was a compound heterozygous for two missense mutations affecting the kinase domain of the insulin receptor beta-subunit (I1115T and R1131W). " 01/01/1989 - "We studied the structure of the insulin-receptor gene in normal individuals and in four unrelated patients with leprechaunism (Minn-1, Ark-1, Ark-2, Can-1) and four unrelated patients with the type A syndrome of insulin resistance, both disorders associated with genetic alterations in affinity, binding capacity, and kinase activity of the insulin receptor. " 08/01/1989 - "To clarify the molecular basis of the insulin resistance, we investigated the insulin binding and kinase properties of the insulin receptor and the receptor gene in cultured skin fibroblasts of two patients (Ark-1 and Ark-2) with leprechaunism and in those of three of their parents. " 03/01/1987 - "To evaluate whether alterations in insulin receptor kinase of erythrocytes can be used as genetic markers, we studied patients with two apparently inherited conditions of severe insulin resistance (leprechaunism and the type A syndrome of insulin resistance) and their families. "
9.	Nonsense Codon (Nonsense Mutation)IBA 09/01/2003 - "A patient with leprechaunism is compound heterozygous for the previously described Arg1092Trp mutation and a nonsense mutation in codon 897. " 10/09/1993 - "Leprechaunism and homozygous nonsense mutation in the insulin receptor gene." 07/31/1993 - "Homozygous nonsense mutation in the insulin receptor gene in infant with leprechaunism." 11/01/1993 - "An in-frame insertion in exon 3 and a nonsense mutation in exon 2 of the insulin receptor gene associated with severe insulin resistance in a patient with Rabson-Mendenhall syndrome." 08/01/1996 - "Homozygous nonsense mutation in the insulin receptor gene of a patient with severe congenital insulin resistance: leprechaunism and the role of the insulin-like growth factor receptor."
10.	Protein-Tyrosine Kinases (Tyrosine Kinase)IBA 12/01/1996 - "The present investigation provides the first evidence that leprechaunism can be causally related to structural alterations in the tyrosine kinase domain of the IR. " 01/01/2012 - "A case of Rabson-Mendenhall syndrome with a novel mutation in the tyrosine kinase domain of the insulin receptor gene complicated by medullary sponge kidney." 08/01/1987 - "Tyrosine kinase activity of insulin receptors from an insulin-resistant patient with leprechaunism." 08/01/2013 - "Donohue syndrome (leprechaunism; OMIM *246200) is a rare, recessively inherited disorder of extreme insulin resistance due to mutations in the insulin receptor gene (INSR) causing either defects in insulin binding or receptor autophosphorylation and tyrosine kinase activity. " 12/01/1996 - "Severe resistance to insulin and insulin-like growth factor-I in cells from a patient with leprechaunism as a result of two mutations in the tyrosine kinase domain of the insulin receptor."

Therapies and Procedures

1.	Subcutaneous Infusions 08/01/2013 - "We report a patient with pronounced clinical picture of leprechaunism who developed severe progressive hypertrophic obstructive cardiomyopathy (HOCM) and renal tubular dysfunction which improved on continuous subcutaneous infusion of recombinant human insulin-like growth factor-1 (rhIGF-I). "
2.	Lasers (Laser) 01/01/2010 - "This clinical case is of interest for 2 reasons: 1) the large retinal neovascularization was likely due to the high insulin dosages; 2) this is the first case in which a sustained regression of retinal neovascularization has been observed after laser treatment in leprechaunism."
3.	Anesthesia 04/01/2007 - "[Managing anesthesia for a woman with Donohue syndrome]."