Kowarski syndrome

Source: Wikipedia, the free encyclopedia.
Kowarski syndrome
Other namesShort stature due to growth hormone qualitative anomaly
This condition is inherited in an autosomal recessive manner.

Kowarski syndrome[1] describes cases of growth failure (height and bone age two standard deviations below the mean for age), despite the presence of normal or slightly high blood growth hormone by radioimmunoassay (RIA-GH) and low serum IGF1 (formerly called somatomedin), and who exhibit a significant increase in growth rate following recombinant GH therapy.[2]

Cause

Allen Avinoam Kowarski et al.

antibodies used in the RIA-GH. Their RIA-GH measured growth hormone of reduced bioactivity. The children retained the ability to respond to treatment with active growth hormone.[citation needed
]

The speculation of Kowarski et al. was confirmed by Valenta et al. in 1985, Takahshi et al. in 1996 and 1997 and Besson et al. in 2005. Valenta et al.

monomers
by urea.

Takahashi et al.

extracellular domain of the GHR. Thus, a dominant-negative effect was observed.[citation needed
]

Takahashi et al.[6] demonstrated in a girl with short stature, a biologically inactive growth hormone resulting from a heterozygous mutation in the GH1 gene. At age 3 years, the girl's height was 3.6 standard deviations below the mean for age and sex. Bone age was delayed by 1.5 years. She had a prominent forehead and a hypoplastic nasal bridge with normal body proportions. She showed lack of growth hormone action despite high immunoassayable GH levels in serum and marked catch-up growth to exogenous GH administration. Results of other studies were compatible with the production of a bioinactive GH, which prevented dimerization of the growth hormone receptor, a crucial step in GH signal transduction.[citation needed]

Besson et al.

parents were each heterozygous for the mutation and were of normal stature.[citation needed
]

Diagnosis

Diagnostic criteria

The discovery of the Kowarski syndrome created a dilemma. The first

diagnostic test for the syndrome was subjecting the suspected children to six month of growth hormone therapy. Kowarski syndrome was assumed to be a very rare disorder (officially recognized as an “orphan disease”). Researchers could not justify subjecting children to a trial period of growth hormone therapy to confirm the diagnosis of a rare syndrome. There is a need for a reliable and practical diagnostic procedure for the syndrome.[citation needed
]

Reliability of testing

The standard test for growth hormone deficiency is the growth hormone stimulation test. Peak levels of growth hormone below normal are considered confirmation of a growth hormone deficiency. Growth-impaired children with a normal stimulation test were considered suspect for having the Kowarski syndrome that may benefit from treatment with growth hormone.[citation needed]

Zadik et al.[8] reported in 1990 that the growth hormone stimulation test is not reliable, suggesting the use of the more reliable 24-hour integrated concentration of growth hormone (IC-GH) as a better test. In 1995, it was also suggested[9] that some cases of the neurosecretory growth failure syndrome might have the Kowarski syndrome.

Albertsson-Wikland Kerstin confirmed in 1992[10] that the IC-GH test is a reproducible test for growth hormone deficiency and Carel et al. confirmed in 1997[11] that the reliability of the growth hormone stimulation tests was poor.

A 1987 study by Bistrizer et al.

radioreceptor assay (RRA-GH) to the level of growth hormone determined by the established radioimmunoassay
(RIA-GH). The study found that the RRA-GH/RIA-GH ratio in NS subjects was normal but significantly below normal (P<0.005) in the Kowarski syndrome patients. The authors proposed the use of their test for the diagnosis of the Kowarski syndrome.

Bistrizer, Chalew and Kowarski demonstrated in 1995 [9] that a modified RRA-GH/RIA-GH ratio test was a predictor for the responsiveness of growth-impaired children to growth hormone therapy.

The RRA-GH/RIA-GH ratio assay proposed by Bistrizer et al.[9] can be used for screening of patients who may have the Kowarski syndrome thus more likely to respond to Growth Hormone therapy. Advances in the methodology for identifying spot mutations in the DNA of individuals demonstrated that the "Kowarski Syndrome is caused by various mutations in the GH1 gene (17q22-q24) that result in structural GH anomalies and a biologically inactive molecule." Testing individual patient for such mutation is offered on the Internet.[13]

References

  1. ^ "OMIM Entry - # 262650 - KOWARSKI SYNDROME". omim.org.
  2. ISBN 9783318022445. {{cite book}}: |first= has generic name (help)CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link
    )
  3. PMID 263308
    .
  4. PMID 3965948
    .
  5. PMID 8552145
    .
  6. PMID 9276733
    .
  7. PMID 15713716
    .
  8. PMID 2229276
    .
  9. ^
    PMID 7607611
    .
  10. PMID 1543014
    .
  11. PMID 9215281
    .
  12. ISSN 0031-3998
    .
  13. ^ "Short stature due to growth hormone qualitative anomaly". orphanet.

External links

Retrieved from "https://en.wikipedia.org/w/index.php?title=Kowarski_syndrome&oldid=1195792409"