| 1. |
|
|
| 2. |
|
|
| 3. |
- David, A, et al.
(författare)
-
Acid-labile subunit deficiency and growth failure: description of two novel cases
- 2010
-
Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 73:5, s. 328-334
-
Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Aims:</i> Mutations in the acid-labile subunit (ALS) gene <i>(IGFALS)</i> have been associated with circulating insulin-like growth factor I (IGF-I) deficiency and short stature. Whether severe pubertal delay is also part of the phenotype remains controversial due to the small number of cases reported. We report 2 children with a history of growth failure due to novel <i>IGFALS</i> mutations. <i>Methods:</i> The growth hormone receptor gene <i>(GHR)</i> and <i>IGFALS</i> were analyzed by direct sequencing. Ternary complex formation was studied by size exclusion chromatography. <i>Results:</i> Two boys of 13.3 and 10.6 years, with pubertal stages 2 and 1, had mild short stature (–3.2 and –2.8 SDS, respectively) and a biochemical profile suggestive of growth hormone resistance. No defects were identified in the <i>GHR</i>. Patient 1 was homozygous for the <i>IGFALS</i> missense mutation P73L. Patient 2 was a compound heterozygote for the missense mutation L134Q and a novel GGC to AG substitution at position 546–548 (546–548delGGCinsAG). The latter causes a frameshift and the appearance of a premature stop codon. Size exclusion chromatography showed no peaks corresponding to ternary and binary complexes in either patient. <i>Conclusion:</i> Screening of the <i>IGFALS</i> is important in children with short stature associated with low serum IGF-I, IGFBP-3 and ALS.
|
|
| 4. |
|
|
| 5. |
- Padidela, R, et al.
(författare)
-
Abnormal growth in noonan syndrome: genetic and endocrine features and optimal treatment
- 2008
-
Ingår i: Hormone research. - : S. Karger AG. - 1423-0046. ; 70:3, s. 129-136
-
Tidskriftsartikel (refereegranskat)abstract
- Noonan syndrome (NS) is a phenotypically heterogeneous syndrome which is frequently associated with short stature. Recent genetic investigations have identified mutations in five genes, namely PTPN11, KRAS, SOS1, NF1 and RAF1 in patients with the NS phenotype. PTPN11 is the commonest, being present in approximately 50% of cases. The degree of short stature in children does not associate closely with the presence of mutations, however some PTPN11-positive patients have decreased GH-dependent growth factors consistent with mild GH insensitivity. GH therapy, using doses similar to those approved for Turner syndrome (TS), induced short-term increases in height velocity over 1–3 years, and may improve final adult height with longer-term treatment.
|
|
| 6. |
|
|
| 7. |
- Savage, MO, et al.
(författare)
-
Early Detection, Referral, Investigation, and Diagnosis of Children with Growth Disorders
- 2016
-
Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 85:5, s. 325-332
-
Tidskriftsartikel (refereegranskat)abstract
- Early diagnosis is a key objective in clinical medicine, and early detection of pathological short stature has tangible benefits for growth prognosis and the well-being of the child. Despite late diagnosis being common in growth disorders, programmes of height screening in primary care are not universal in developed countries and may be random or non-existent. A notable exception is automated growth monitoring in Finland, where an algorithm to detect abnormal growth is integrated into children's electronic health records, resulting in increased diagnoses of pathological short stature. Evidence-based anthropometric criteria for referral of short stature to secondary or tertiary care are now published, due largely to excellent studies in the Netherlands. Following referral of the short child, the protocol for laboratory investigations remains somewhat controversial because in healthy children their diagnostic yield can be too low for cost-effectiveness. However, outside of tertiary academic paediatric endocrinology centres, baseline screening tests are considered worthwhile and may speed up diagnosis and treatment. Finally, auxological cut-offs cannot replace good clinical practice, and the understanding that early and effective management depends on commitment to a diagnosis and individualisation of therapy in the short child cannot be overemphasised.
|
|
| 8. |
|
|
