ESPE Abstracts

Background: Mutations in POU1F1 is a rare cause of combined pituitary hormone deficiency, which commonly includes GH, TSH and prolactin deficiencies and characterised by hypoplastic anterior pituitary.

Objective and hypotheses: To present a case of severe short stature and developmental delay 1.5 years old girl, who was admitted to our hospital because of short stature.

Method: Hypopituitarism panel’ genes were sequenced using a custom Ion Ampliseq gene panel and PGM semiconductor sequencer (Ion Torrent).

Results: The girl was born at term from consanguineous healthy parents. Her birth length and weight were 47 cm and 2220 g respectively. Psycho-motor delay were noted during first months of life. Cardiac echo showed patent ductus arteriosus at 1^st week of life and patient underwent surgery at 5 months. She was diagnosed with central hypothyroidism at 2 months of age and started on Levothyroxine. Since then her fT₄ levels were always normal. At 1.5 years her height was 58 cm (S.D.s −7.3) and her weight was 3.8 kg (BMI S.D.s −7.4), she had severe developmental delay and some mild dysmorphic features (sparse hair, prominent forehead, saddle nose and blue sclera). Laboratory testing revealed recurrent asymptomatic ketotic hypoglycaemias (1.4–2.6 mmol/l), low IGF1 (3 ng/ml), undetectable prolactin (<30 mU/l), but normal random cortisol and ACTH levels (495 nmol/l and 12.7 pg/ml respectively). Brain MRI showed anterior pituitary hypoplasia. Genetic analysis revealed homozygous R256W mutation in POU1F1 gene. The girl was started on GH therapy (Rastan) and carbohydrate rich diet. For the first 5 months of GH therapy she grew 9 cm (height velocity 19 cm/year) and showed some improvement in psychomotor development, but remained hypotrophic (BMI S.D.s −5.2).

Conclusion: POU1F1 mutations is a rare cause of hypopituitarism, which may present with failure to thrive and extremely short stature, showing a good response to GH therapy. Severe developmental delay, seen in our case, may be a result of untreated neonatal hypoglycaemia, hypothyroidism or be a part of a syndrome.