| Laron syndrome |
| Classification and external resources |
Growth hormone |
| ICD-10 |
E34.3 |
| ICD-9 |
259.4 |
| OMIM |
262500 245590 |
| DiseasesDB |
7262 |
| eMedicine |
ped/1277 |
| MeSH |
D046150 |
Laron syndrome, or Laron-type dwarfism, is an autosomal recessive disorder characterized by an insensitivity to growth hormone (GH), caused by a variant of the growth hormone receptor. It causes short stature and a resistance to diabetes and cancer.
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Contents
- 1 Eponym
- 2 Pathophysiology
- 3 Clinical characteristics
- 4 Treatment
- 5 Prognosis
- 6 Homo floresiensis
- 7 References
- 8 External links
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Eponym
It is named after Zvi Laron, the Israeli researcher who, with A. Pertzelan and S. Mannheimer, first reported the condition in 1966,[1][2] based upon observations which began in 1958.[3]
Resistance to GH was first reported by Laron in 1966. Since then, severe resistance to GH, characterized by grossly impaired growth despite normal levels of GH in serum, has been termed Laron syndrome.
Pathophysiology
Laron syndrome has an autosomal recessive pattern of inheritance.
Molecular genetic investigations have shown that this disorder is mainly associated with mutations in the gene for the GH receptor. These can result in defective hormone binding to the ectodomain or reduced efficiency of dimerization of the receptor after hormone occupancy. There are exceptionally low levels of insulin-like growth factor (IGF-1) and its principal carrier protein, insulin-like growth factor binding protein 3.
A related condition involving postreceptor insensitivity to growth hormone has been associated with STAT5B.[4]
Clinical characteristics
The principal feature of Laron syndrome is abnormally short stature (dwarfism). Physical symptoms include: prominent forehead, depressed nasal bridge, underdevelopment of mandible, truncal obesity[5] and a very small penis. Seizures are frequently seen secondary to hypoglycemia. Some genetic variations have an impact upon intellectual capacity.[6]
The majority of reported cases have been of Arabic or Semitic origin, with numerous patients in Israel, Saudi Arabia, Egypt, Iraq, and remote villages in Ecuador with Sephardic roots.[7][8]
In 2011, it was reported that people with this syndrome in the Ecuadorian villages are resistant to cancer and diabetes and are somewhat protected against aging.[7][9][10] This is consistent with findings in mice with a defective growth hormone receptor gene.[8]
Treatment
Administration of GH has no effect on IGF-1 production, therefore treatment is mainly by biosynthetic IGF-1. IGF-1 must be taken before puberty to be effective.[8]
IPLEX (Mecasermin rinfabate) is composed of recombinant human IGF-1 (rhIGF-1) and its binding protein IGFBP-3. It was approved by the U.S. Food and Drug Administration (FDA) in 2005 for treatment of primary IGF-1 deficiency or GH gene deletion.[11][12] Side effects from IPLEX are hypoglycemia.
IPLEX's manufacturing company, Insmed, can no longer develop proteins and can no longer manufacture IPLEX as of a statement released in January 2012.
Prognosis
People with Laron syndrome have strikingly low rates of cancer and diabetes.[8]
Homo floresiensis
Recent publications have proposed that Homo floresiensis represented a population with widespread Laron syndrome.[13][14] This hypothesis has received criticism and is unconfirmed.
References
- ^ synd/2825 at Who Named It?
- ^ Laron Z, Pertzelan A, Mannheimer S (1966). "Genetic pituitary dwarfism with high serum concentration of growth hormone—a new inborn error of metabolism?". Isr. J. Med. Sci. 2 (2): 152–5. PMID 5916640.
- ^ Laron Z (2004). "Laron syndrome (primary growth hormone resistance or insensitivity): the personal experience 1958–2003". J. Clin. Endocrinol. Metab. 89 (3): 1031–44. doi:10.1210/jc.2003-031033. PMID 15001582.
- ^ Hwa V, Camacho-Hübner C, Little BM, et al. (2007). "Growth hormone insensitivity and severe short stature in siblings: a novel mutation at the exon 13-intron 13 junction of the STAT5b gene". Horm. Res. 68 (5): 218–24. doi:10.1159/000101334. PMID 17389811. http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=000101334.
- ^ Laron Z, Ginsberg S, Lilos P, Arbiv M, Vaisman N (2006). "Body composition in untreated adult patients with Laron syndrome (primary GH insensitivity)". Clin. Endocrinol. (Oxf) 65 (1): 114–7. doi:10.1111/j.1365-2265.2006.02558.x. PMID 16817829.
- ^ Shevah O, Kornreich L, Galatzer A, Laron Z (2005). "The intellectual capacity of patients with Laron syndrome (LS) differs with various molecular defects of the growth hormone receptor gene. Correlation with CNS abnormalities". Horm. Metab. Res. 37 (12): 757–60. doi:10.1055/s-2005-921097. PMID 16372230.
- ^ a b Guevara-Aguirre, J; Balasubramanian, P; Guevara-Aguirre, M; Wei, M; Madia, F; Cheng, CW; Hwang, D; Martin-Montalvo, A et al. (2011). "Growth Hormone Receptor Deficiency Is Associated with a Major Reduction in Pro-Aging Signaling, Cancer, and Diabetes in Humans". Science Translational Medicine 3 (70): 70ra13. doi:10.1126/scitranslmed.3001845. PMC 3357623. PMID 21325617. http://stm.sciencemag.org/content/3/70/70ra13.abstract.
- ^ a b c d Wade, Nicholas (17 February 2011). "Ecuadorean Villagers May Hold Secret to Longevity". The New York Times. ISSN 0362-4331. http://www.nytimes.com/2011/02/17/science/17longevity.html?_r=1&hpw. Retrieved 17 February 2011.
- ^ Bai, Nina. "Defective Growth Gene in Rare Dwarfism Disorder Stunts Cancer and Diabetes". Scientific American. http://www.scientificamerican.com/article.cfm?id=defective-growth-gene-in-dwarfism. Retrieved 17 February 2011.
- ^ Winerman, Lea. "Study: Dwarfism Gene May Offer Protection From Cancer, Diabetes". PBS. http://www.pbs.org/newshour/rundown/2011/02/dwarfism-gene-may-offer-protection-from-cancer-diabetes.html. Retrieved 17 February 2011.
- ^ Kemp, S.F.. "Mecasermin rinfabate". Thomson Reuters. http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=4&p_RefId=1079876&p_IsPs=N. Retrieved 5 March 2011.
- ^ Meyer, Robert. "Approval letter (Mecasermin rinfabate)". FDA. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021884_s000_Iplex_Approv.pdf. Retrieved 5 March 2011.
- ^ Hershkovitz I, Kornreich L, Laron Z (2007). "Comparative skeletal features between Homo floresiensis and patients with primary growth hormone insensitivity (Laron syndrome)". Am. J. Phys. Anthropol. 134 (2): 198–208. doi:10.1002/ajpa.20655. PMID 17596857.
- ^ Culotta E (2007). "Paleoanthropology. The fellowship of the hobbit". Science 317 (5839): 740–742. doi:10.1126/science.317.5839.740. PMID 17690271.
External links
- Laron+syndrome at the US National Library of Medicine Medical Subject Headings (MeSH)
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Endocrine pathology: endocrine diseases (E00–E35, 240–259)
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Pancreas/
glucose
metabolism |
| Hypofunction |
- types:
- type 1
- type 2
- MODY 1 2 3 4 5 6
- complications
- coma
- angiopathy
- ketoacidosis
- nephropathy
- neuropathy
- retinopathy
- cardiomyopathy
- insulin receptor (Rabson–Mendenhall syndrome)
- Insulin resistance
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| Hyperfunction |
- Hypoglycemia
- beta cell (Hyperinsulinism)
- G cell (Zollinger–Ellison syndrome)
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Hypothalamic/
pituitary axes |
| Hypothalamus |
- gonadotropin
- Kallmann syndrome
- Adiposogenital dystrophy
- CRH (Tertiary adrenal insufficiency)
- vasopressin (Neurogenic diabetes insipidus)
- general (Hypothalamic hamartoma)
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| Pituitary |
| Hyperpituitarism |
- anterior
- Acromegaly
- Hyperprolactinaemia
- Pituitary ACTH hypersecretion
- posterior (SIADH)
- general (Nelson's syndrome)
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| Hypopituitarism |
- anterior
- Kallmann syndrome
- Growth hormone deficiency
- ACTH deficiency/Secondary adrenal insufficiency
- GnRH insensitivity
- FSH insensitivity
- LH/hCG insensitivity
- posterior (Neurogenic diabetes insipidus)
- general
- Empty sella syndrome
- Pituitary apoplexy
- Sheehan's syndrome
- Lymphocytic hypophysitis
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| Thyroid |
| Hypothyroidism |
- Iodine deficiency
- Cretinism
- Congenital hypothyroidism
- Myxedema
- Euthyroid sick syndrome
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| Hyperthyroidism |
- Hyperthyroxinemia
- Thyroid hormone resistance
- Familial dysalbuminemic hyperthyroxinemia
- Hashitoxicosis
- Thyrotoxicosis factitia
- Graves' disease
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| Thyroiditis |
- Acute infectious
- Subacute
- De Quervain's
- Subacute lymphocytic
- Autoimmune/chronic
- Hashimoto's
- Postpartum
- Riedel's
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| Goitre |
- Endemic goitre
- Toxic nodular goitre
- Toxic multinodular goiter
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| Parathyroid |
| Hypoparathyroidism |
- Hypoparathyroidism
- Pseudohypoparathyroidism
- Pseudopseudohypoparathyroidism
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| Hyperparathyroidism |
- Primary
- Secondary
- Tertiary
- Osteitis fibrosa cystica
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| Adrenal |
| Hyperfunction |
- aldosterone: Hyperaldosteronism/Primary aldosteronism
- Conn syndrome
- Bartter syndrome
- Glucocorticoid remediable aldosteronism
- AME
- Liddle's syndrome
- 17α CAH
- cortisol: Cushing's syndrome (Pseudo-Cushing's syndrome)
- sex hormones: 21α CAH
- 11β CAH
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Hypofunction/
Adrenal insufficiency
(Addison's, WF) |
- aldosterone: Hypoaldosteronism
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| Gonads |
- ovarian: Polycystic ovary syndrome
- Premature ovarian failure
- testicular: enzymatic
- 5α-reductase deficiency
- 17β-hydroxysteroid dehydrogenase deficiency
- aromatase excess syndrome)
- Androgen receptor (Androgen insensitivity syndrome
- general: Hypogonadism (Delayed puberty)
- Hypergonadism
- Hypoandrogenism
- Hypoestrogenism
- Hyperandrogenism
- Hyperestrogenism
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| Height |
- Dwarfism/Short stature
- Laron syndrome
- Psychosocial
- Gigantism
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| Multiple |
- Autoimmune polyendocrine syndrome
- Carcinoid syndrome
- Multiple endocrine neoplasia
- Progeria
- Werner syndrome
- Acrogeria
- Metageria
- Woodhouse-Sakati syndrome
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noco (d)/cong/tumr, sysi/epon
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proc, drug (A10/H1/H2/H3/H5)
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Genetic disorder, membrane: cell surface receptor deficiencies
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G protein-coupled receptor
(including hormone) |
| Class A |
- TSHR (Congenital hypothyroidism 1)
- LHCGR (Male-limited precocious puberty)
- FSHR (XX gonadal dysgenesis)
- EDNRB (ABCD syndrome, Waardenburg syndrome 4a, Hirschsprung's disease 2)
- AVPR2 (Nephrogenic diabetes insipidus 1)
- PTGER2 (Aspirin-induced asthma)
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| Class B |
- PTH1R (Jansen's metaphyseal chondrodysplasia)
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| Class C |
- CASR (Familial hypocalciuric hypercalcemia)
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| Class F |
- FZD4 (Familial exudative vitreoretinopathy 1)
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Enzyme-linked receptor
(including
growth factor) |
| RTK |
- ROR2 (Robinow syndrome)
- FGFR1 (Pfeiffer syndrome, KAL2 Kallmann syndrome)
- FGFR2 (Apert syndrome, Antley-Bixler syndrome, Pfeiffer syndrome, Crouzon syndrome, Jackson-Weiss syndrome)
- FGFR3 (Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia, Muenke syndrome)
- INSR (Donohue syndrome
- Rabson–Mendenhall syndrome)
- NTRK1 (Congenital insensitivity to pain with anhidrosis)
- KIT (KIT Piebaldism, Gastrointestinal stromal tumor)
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| STPK |
- AMHR2 (Persistent Mullerian duct syndrome II)
- TGF beta receptors: Endoglin/Alk-1/SMAD4 (Hereditary hemorrhagic telangiectasia)
- TGFBR1/TGFBR2 (Loeys-Dietz syndrome)
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| GC |
- GUCY2D (Leber's congenital amaurosis 1)
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| JAK-STAT |
- Type I cytokine receptor: GH (Laron syndrome)
- CSF2RA (Surfactant metabolism dysfunction 4)
- MPL (Congenital amegakaryocytic thrombocytopenia)
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| TNF receptor |
- TNFRSF1A (TNF receptor associated periodic syndrome)
- TNFRSF13B (Selective immunoglobulin A deficiency 2)
- TNFRSF5 (Hyper-IgM syndrome type 3)
- TNFRSF13C (CVID4)
- TNFRSF13B (CVID2)
- TNFRSF6 (Autoimmune lymphoproliferative syndrome 1A)
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| Lipid receptor |
- LRP: LRP2 (Donnai-Barrow syndrome)
- LRP4 (Cenani Lenz syndactylism)
- LRP5 (Worth syndrome, Familial exudative vitreoretinopathy 4, Osteopetrosis 1)
- LDLR (LDLR Familial hypercholesterolemia)
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| Other/ungrouped |
- Immunoglobulin superfamily: AGM3, 6
- Integrin: LAD1
- Glanzmann's thrombasthenia
- Junctional epidermolysis bullosa with pyloric atresia
EDAR (EDAR Hypohidrotic ectodermal dysplasia)
- PTCH1 (Nevoid basal cell carcinoma syndrome)
- BMPR1A (BMPR1A Juvenile polyposis syndrome)
- IL2RG (X-linked severe combined immunodeficiency)
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- See also
- cell surface receptors
- B structural
- perx
- skel
- cili
- mito
- nucl
- sclr
- DNA/RNA/protein synthesis
- membrane
- transduction
- trfk
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