Isolated growth hormone deficiency type IA due to a novel GH1 variant: a case report

Background A case of isolated growth hormone deficiency type IA (IGHD IA) caused by novel compound heterozygous mutation in the GH1 gene was reported in this study, which aimed to provide insights that will benefit future diagnosis and treatment. Case presentation We analyzed and summarized the clinical data and genetic test results from a patient with IGHD admitted in March 2019 to the Department of Pediatrics Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. We described the results from a 1-year-9-months old female, whose chief complaint was “growth retardation for more than one year”. Her birth length was 49.0 cm, and her birth weight was 3.05 kg. Suboptimal intake (breastfeeding) jaundice lasted for approximately two months following birth. When evaluated at the age of 1-year-9-months old, the patient’s height was 61.0 cm (− 7.24 SD), and her weight was 6.4 kg (− 1.50 SD). The patient’s physical characteristics included yellowish hair, large and unclosed anterior fontanelles, raised forehead, and a low and flat nose. The major abnormalities observed from the auxiliary examinations included low GH (< 0.05 μg/l), low IGF-1 (16.99 μg/l), and elevated TSH (6.97 mIU/l). Genetic testing revealed two heterozygous variants: a splicing mutation (NG_011676.1(NM_022560.4): c.10 + 1G>T, inherited from her mother) in intron 1 of the GH1 gene and a deletion that encompassed the same gene (chr17: 61973811–61996255, inherited from her father). After hormone replacement therapy with L-thyroxine and recombinant human GH (rhGH), the patient’s thyroid function returned to normal, and her serum IGF-1 level significantly improved, which resulted in an accelerated increase in height. Conclusion This study described a case of IGHD caused by novel compound heterozygous mutations in the GH1 gene. This study suggested that closer attention should be directed to genetic testing and diagnosis based on clinical characteristics to avoid misdiagnosis.

Questioning the Value of Brain Magnetic Resonance Imaging in the Evaluation of Children with Isolated Growth Hormone Deficiency

<b><i>Background:</i></b> Isolated growth hormone deficiency (IGHD) is a relatively common disorder. Current diagnostic protocol requires a brain magnetic resonance imaging (MRI) study of the hypothalamus and the hypophysis to determine the cause after establishment of the diagnosis. This study aimed to examine the yield of brain MRI in the evaluation of children with IGHD and to define clinical and laboratory parameters that justify its performance. <b><i>Methods:</i></b> A retrospective chart review of all children (&#x3c;18 years) diagnosed with IGHD was conducted at 3 pediatric endocrinology units between 2008 and 2018. <b><i>Results:</i></b> The study included 192 children (107 boys) with confirmed IGHD. The mean age ± standard deviation (SD) at diagnosis was 8.2 ± 3.7 years (median 8.5 years, range 0.8–15.9). The mean height SD score (SDS) at diagnosis was –2.25 ± 0.73. The mean height deficit SDS (defined as the difference between height SDS at diagnosis and mid-parental height SDS) was –1.7 ± 0.9. Fifteen children (7.8%) had pathological MRI findings. No space-occupying lesion was detected. Children with pathological MRIs had greater height deficit SDS and lower peak growth hormone levels on provocative tests compared to children with normal MRIs: –2.3 ± 1.2 vs. –1.6 ± 0.8 (<i>p</i> = 0.02) and 4.4 ± 1.9 vs. 5.7 ± 1.3 (<i>p</i> = 0.01), respectively. <b><i>Conclusion:</i></b> Our preliminary data indicate that most brain MRIs performed for routine evaluation of children with IGHD are not essential for determining cause. Further studies with larger cohorts are needed in order to validate this proposed revision of current protocols.