Endocrine Abstracts

JOINT1020

Objective: We report the clinical characteristics, diagnosis, and genetic analysis of a case of familial progressive hyperpigmentation and hypopigmentation (FHPP).

Methods: The clinical information of a 2-year-old girl with “hyperpigmentation since birth” was retrospectively reported. Whole exome sequencing analysis was performed on DNA extracted from peripheral blood and skin tissue. Candidate variant was verified by Sanger sequencing of her parents.

Results: A Chinese girl with uniform hyperpigmentation was noted since birth. She was born to healthy nonconsanguineous parents, following an uneventful pregnancy. At 2-month-old, blood tests revealed potassium levels of 6.06 mmol/l, sodium levels of 134.6 mmol/l, ACTH levels of 73.85 pg/ml, cortisol levels of 17.78 ug/dl, 17α-hydroxyprogesterone <0.2 ng/ml, and progesterone <0.05 ng/ml. Adrenal ultrasound and CT scans showed normal and the chromosome karyotyping showed 46, XX. She was initially diagnosed with primary adrenal insufficiency and started on hydrocortisone replacement therapy at a dose of 40 mg/m².d. Subsequently regular follow-up showed normal electrolyte levels, with ACTH level fluctuating between 1.5-12.4 pg/ml. The hydrocortisone dose was gradually reduced to 1.5 mg/day (2.6 mg/m².d). The child did not experience any salt-losing crises, but the hyperpigmentation gradually progressed. At 2-year-old, she was re-evaluated in our endocrinology department. Physical examination revealed a height of 90 cm (P25-50), weight of 12 kg (P25). Her trunk showed general hyperpigmentation, especially in the areolas and skin folds, with some superimposed irregular café –au–lait spots. Hypopigmented macules were also seen on the trunk. The level of ACTH, electrolyte and blood gas analysis were rechecked and showed normal after discontinuing hydrocortisone. The ACTH stimulation test indicated normal adrenal cortical function, then hydrocortisone treatment was continuous discontinued. Whole exome sequencing of peripheral blood and skin tissue revealed a heterozygous c.100A>C (p.Thr34Pro) variant of the KITLG gene, which was not present in her unaffected parents. The latest follow-up, conducted 1.5 years after discontinuing hydrocortisone (when she was 4-year-old), showed no salt loss crises. Her height and weight were both at average levels, and the hyperpigmentation became more noticeable with age.

Conclusion: Hyperpigmentation is a characteristic of many clinical diseases and can be challenging to diagnose. For infants with progressive skin pigmentation and hypopigmentation spots, FPHH caused by KITLG gene heterozygous variants should be considered.