Endocrine Abstracts

JOINT1585

Objective: Alstrom syndrome is a hereditary disorder caused by a double dose of a mutated gene. This leads to clinical manifestations including retinal degeneration (resulting in blindness), obesity, TD2M, neurosensory hearing loss, and early-onset dilated cardiomyopathy. Currently, only one gene has been identified as causing this syndrome: ALMS1. We present a clinical case of a patient with Alstrom syndrome as encountered by an endocrinologist.

Materials and Methods: Patient A.A., an 18-year-old male, presented to the endocrinologist complaining of a 3-4 kg weight gain over the past 6 months, decreased visual acuity since childhood, photophobia, hearing loss, and short stature. At age 1 year, an ophthalmological examination revealed nystagmus, photophobia, low visual acuity and hereditary retinal dystrophy and mixed astigmatis. Usher syndrome was suspected but excluded through genetic testing. He has been overweight since childhood. At age 14, an audiological examination revealed grade 2 progressive neurosensory hearing loss. At age 17, he consulted an endocrinologist due to short stature (158 cm). His father is 180 cm tall, his mother 164 cm, his older brother 189 cm. Hand X-rays showed a bone age consistent with 17-18 years. Pituitary MRI revealed no adenoma. At age 18, Alstrom syndrome was genetically confirmed. In 2024, at Endocrinology Research Center the examination revealed a weight of 85.4 kg, height of 158 cm, and BMI of 34.1 kg/m². He had brown striae on his upper extremities, minimal body and facial hair, and firm breasts on palpation. Hormonal testing excluded endocrine causes of obesity (endogenius hypercortisolism, hyperprolactinemia, and hypothyroidism). Normogonadotropic hypogonadism was diagnosed (LH 5.6 IU/l, FSH 11.6 IU/l, total testosterone 4.85 nmol/L). An urological consultation diagnosed secretory infertility, and hormone replacement therapy was recommended. Growth hormone deficiency was ruled out (GH 0.18 ng/ml, IGF-1 260.8 ng/ml). There was no evidence of impaired glucose metabolism. Orlistat was recommended to manage his weight and prevent progression of dysmetabolic complications. An ophthalmological consultation confirmed Alstrom-Hallgren syndrome, with findings of tapetretinal abiotrophy, partial optic nerve atrophy, horizontal nystagmus, convergent strabismus, and early posterior capsular cataract. Significantly, ECG did not reveal dilated cardiomyopathy.

Conclusion: The ALMS1 gene mutation underlies the patient’s reduced vision, hearing, obesity, diabetes, and short stature, significantly impacting his quality of life and lifespan. This presents a significant social problem. This clinical case highlights the importance of early diagnosis of genetic disorders by primary care physicians and the need for a multidisciplinary approach in managing patients with rare diseases.