Recurrent hypoglycemia due to growth hormone deficiency in an infant with Turner syndrome

TY - JOUR

T1 - Recurrent hypoglycemia due to growth hormone deficiency in an infant with Turner syndrome

AU - Bonfig, Walter

AU - Salem, Nabeel J M

AU - Heiliger, Katrin

AU - Hempel, Maja

AU - Lederer, Gaby

AU - Bornkamm, Milena

AU - Wieland, Karen

AU - Lohse, Peter

AU - Burdach, Stefan

AU - Oexle, Konrad

PY - 2012

Y1 - 2012

N2 - BACKGROUND: Growth hormone (GH) deficiency may occur in Turner syndrome (TS), but infantile hypoglycemia attributable to TS with GH deficiency has not been reported before.OBJECTIVES: We report a puzzling case of neonatal hypoglycemia due to GH deficiency in Turner syndrome. Array CGH was used to scrutinize the complex TS karyotype.METHODS: Standardized laboratory procedures.RESULTS: In a preterm (32 weeks) with prolonged and cholestatic jaundice, recurrent hypoglycemia occurred at the age of 1.5 months and was related to GH deficiency. There were no other endocrine or syndromic features. GH therapy was started at a usual dose of 25-30 μg/kg/day, but hypoglycemia recurred. Hepatopathy and hypogammaglobulinemia suggested X-recessive GH deficiency type 3 with non-random X-inactivation but resolved spontaneously. Nonetheless, a 45,X[75]/46,X,i(Xq)[21]/47,X,i(Xq)x2[4] TS karyotype was diagnosed with an apparent isochromosome fusion at the centromere. Upon this diagnosis, GH dose was doubled (50 μg/kg/day), and blood glucose was normalized consistently. In array CGH, the signal of Xp deviated more strongly than that of Xq, but the relation of the signals differed substantially from what the karyotype predicted. The isochromosome fusion point was relocated to Xp11.22, distal to a block of mental retardation genes that escape X-inactivation.CONCLUSIONS: i) TS with GH deficiency should be considered as a potential differential diagnosis of hypoglycemia in infants requiring higher doses of GH. ii) While array CGH may be erroneous in quantification of TS mosaicism, it is useful in precisely delineating isochromosomes and identifying genes on them that escape X-inactivation and thus possibly affect the TS phenotype.

AB - BACKGROUND: Growth hormone (GH) deficiency may occur in Turner syndrome (TS), but infantile hypoglycemia attributable to TS with GH deficiency has not been reported before.OBJECTIVES: We report a puzzling case of neonatal hypoglycemia due to GH deficiency in Turner syndrome. Array CGH was used to scrutinize the complex TS karyotype.METHODS: Standardized laboratory procedures.RESULTS: In a preterm (32 weeks) with prolonged and cholestatic jaundice, recurrent hypoglycemia occurred at the age of 1.5 months and was related to GH deficiency. There were no other endocrine or syndromic features. GH therapy was started at a usual dose of 25-30 μg/kg/day, but hypoglycemia recurred. Hepatopathy and hypogammaglobulinemia suggested X-recessive GH deficiency type 3 with non-random X-inactivation but resolved spontaneously. Nonetheless, a 45,X[75]/46,X,i(Xq)[21]/47,X,i(Xq)x2[4] TS karyotype was diagnosed with an apparent isochromosome fusion at the centromere. Upon this diagnosis, GH dose was doubled (50 μg/kg/day), and blood glucose was normalized consistently. In array CGH, the signal of Xp deviated more strongly than that of Xq, but the relation of the signals differed substantially from what the karyotype predicted. The isochromosome fusion point was relocated to Xp11.22, distal to a block of mental retardation genes that escape X-inactivation.CONCLUSIONS: i) TS with GH deficiency should be considered as a potential differential diagnosis of hypoglycemia in infants requiring higher doses of GH. ii) While array CGH may be erroneous in quantification of TS mosaicism, it is useful in precisely delineating isochromosomes and identifying genes on them that escape X-inactivation and thus possibly affect the TS phenotype.

KW - Comparative Genomic Hybridization

KW - Human Growth Hormone

KW - Humans

KW - Hypoglycemia

KW - Infant

KW - Recurrence

KW - Turner Syndrome

KW - X Chromosome Inactivation

U2 - 10.1515/jpem-2012-0103

DO - 10.1515/jpem-2012-0103

M3 - SCORING: Journal article

C2 - 23426831

VL - 25

SP - 991

EP - 995

JO - J PEDIATR ENDOCR MET

JF - J PEDIATR ENDOCR MET

SN - 0334-018X

IS - 9-10

ER -