GH INSENSITIVITY IN A PATIENT COMPOUND HETEROZYGOUS FOR A NOVEL AND A RECURRENT GHR GENE MUTATION. LONG TERM EFFECT OF RHIGF-I TREATMENT.

PAULA A.. SCAGLIA; MARÍA ARRIAZU; P. GONZÁLEZ AGUILAR; HORACIO M. DOMENÉ

Mar del Plata, Argentina

Congreso; XIX Reunión anual de la Sociedad Latinoamerican de Endocrinología Pediátrica; 2007

Sociedad Latinoamerican de Endocrinología Pediátrica

GH INSENSITIVITY IN A PATIENT COMPOUND HETEROZYGOUS FOR A NOVEL AND A RECURRENT GHR GENE MUTATION. LONG TERM EFFECT OF RHIGF-I TREATMENT. P. Scaglia1, M. Arriazu2, P. González Aguilar2, H. Domené1, 1 CEDIE-CONICET, Hospital de Niños R. Gutiérrez, Buenos Aires, Argentina 2 Hospital Privado De La Comunidad, Mar Del Plata, Argentina GH insensitivity (GHI) is characterized by severe post-natal growth impairment, IGF-I deficiency, and normal or elevated GH levels. We describe a male patient, the second child from non-consanguineous parents, birth weight 3420 g, birth length 47.5 cm, presenting many dysmorphic features: flat nasal bridge, bilateral convergent strabismus, frontal bossing, and acromicria. At 1 year of age, the diagnosis of GHI was performed based on high basal and stimulated GH levels, undetectable levels of GHBP and IGF-I, with no response of IGF-I to 4 day rhGH treatment (0.1 mg/kg.dose). DNA sequencing of GHR gene revealed two different mutations: a 17 bp deletion in exon 5 [c.328_344del (p.N92FfsX16)] and a point mutation in exon 7 [c.723C>T (p.G223G)]. The parents were heterozygous carriers for one mutated allele (father: p.N92FfsX16; mother p.G223G), while his brother had both wild-type alleles. At the age of 2.6 years (height 69 cm; -5.8 SDS) treatment with rhIGF-I (120 µg/d) was started, attaining a height of 155 cm (-2.4 SDS) at the age of 17.1 years. Triptoreline treatment was added at 12.3 years to prevent pubertal progression. The point mutation in exon 7, which creates a new preferred splicing site, has previously been described in GHI patients from a genetic isolate in the Bahamas, in one patient from Spain, and in two in Argentina. In conclusion, the p.G223G recurrent mutation should be routinely investigated by restriction enzyme digestion in patients with GHI. Early and prolonged rhIGF-I treatment are important to attain a height close to the normal range.