Unraveling the Diagnostic Puzzle of Hermansky-Pudlak Syndrome: Lessons from Two Brothers with Growth Failure

Abstract

Short stature (SS) is a common reason for consultation in pediatric endocrinology. Its etiologies are varied, with general causes predominating, while endocrine causes account for only about 10% of cases. More rarely, SS may occur in a syndromic context, making diagnosis more complex. Early identification of such cases is crucial for appropriate management and to limit long-term repercussions.

We report the cases of two brothers, aged 7 and 9 years, referred for evaluation of SS. Both presented with height and weight below -2 standard deviations for age and sex. Clinical and radiological examinations revealed recurrent epistaxis, micrognathia with broad nasal bridge, oculocutaneous albinism, a polymalformative syndrome including spondyloepiphyseal dysplasia, dorsolumbar scoliosis, and equinovarus foot, and limited joint mobility in the upper and lower limbs. IGF-1 levels were below age- and sex-matched norms. A stimulation test with Avlocardyl®-glucagon confirmed growth hormone (GH) deficiency. Hypothalamic-pituitary MRI was normal. The short stature in these two brothers occurs in a complex syndromic context. The association of oculocutaneous albinism, osteoarticular malformations, and growth hormone deficiency strongly suggests Hermansky-Pudlak syndrome (HPS), a rare genetic disease characterized by albinism and other systemic anomalies. To our knowledge, this is the first report of HPS presenting with growth hormone deficiency in two brothers from North Africa. Diagnosis relies on multidisciplinary evaluation and ideally genetic confirmation. Management requires orthopedic correction of malformations, specialized ophthalmological follow-up, and psychosocial support. GH replacement therapy is contraindicated due to the risk of aggravating bone abnormalities.

Early recognition of a rare etiology like Hermansky-Pudlak syndrome enables targeted management, which is essential to improve functional prognosis and quality of life.