Clinical and biochemical characteristics and bone mineral density of homozygous, compound heterozygous and heterozygous carriers of three novel IGFALS mutations.
Eur J Endocrinol
; 176(6): 657-667, 2017 Jun.
Article
em En
| MEDLINE
| ID: mdl-28249955
ABSTRACT
OBJECTIVE:
Acid-labile subunit (ALS) deficiency (ACLSD), caused by homozygous or compound heterozygous IGFALS mutations, is associated with moderate short stature, delayed puberty, low serum IGF-I and ALS and extremely low serum IGFBP-3. Its effect on birth weight, head circumference, bone mineral density (BMD), serum IGF-II and IGFBP-2 is uncertain, as well as the phenotype of heterozygous carriers of IGFALS mutations (partial ACLSD).DESIGN:
From all available members of five Turkish families, carrying three mutations in exon 2 of IGFALS (c.1462G > A, p.Asp488Asn (families A, B, E); c.251A > G, p.Asn84Ser (families C and E) and c.1477del, p.Arg493fs (family D)), clinical, laboratory and BMD data were collected.METHODS:
Auxological and biochemical findings were expressed as SDS for age and gender. Ternary complex formation in serum was investigated by size-exclusion chromatography. BMD using DXA bone densitometry was adjusted for height and age (Ha-BMD z-score).RESULTS:
In ACLSD (n = 24), mean ± s.d. height SDS (-2.7 ± 1.2), head circumference SDS (-2.3 ± 0.5) and body mass index (BMI) (-0.6 ± 1.0 SDS) were lower than those in partial ACLSD (n = 26, P ≤ 0.01) and birth weight SDS (n = 7) tended to be lower (-2.2 ± 1.1 vs -0.6 ± 0.3 in partial ACLSD (P = 0.07)). Serum IGF-I was -3.7 ± 1.4 vs -1.0 ± 1.0, IGF-II -5.6 ± 0.7 vs -1.3 ± 0.7, ALS <-4.4 ± 1.2 vs -2.1 ± 0.9 and IGFBP-3 -9.0 ± 1.9 vs -1.6 ± 0.8 SDS respectively (P < 0.001). Ha-BMD z-score was similar and normal in both groups.CONCLUSIONS:
To the known phenotype of ACLSD (i.e. short stature, reduced serum levels of IGF-I and ALS, extremely low serum IGFBP-3 and disturbed ternary complex formation), we add reduced birth weight, head circumference and serum IGF-II.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Insulin-Like I
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Fator de Crescimento Insulin-Like II
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Glicoproteínas
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Proteínas de Transporte
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Densidade Óssea
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Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina
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Transtornos do Crescimento
Limite:
Adolescent
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Child
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Female
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Humans
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Male
País/Região como assunto:
Asia
Idioma:
En
Revista:
Eur J Endocrinol
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Turquia