ESPE Abstracts

Introduction: Alstrom syndrome (ALMS) is an autosomal recessive disorder characterized by multiple organ involvement, including progressive cone-rod dystrophy, sensorineural hearing loss, childhood obesity, and type 2 diabetes mellitus. Pathogenic variants in the ALMS1 gene are the known cause for the occurrence of this devastating condition. Here, we reported a case of Alstrom syndrome with a novel homozygous variant in the ALMS gene, who presented to our clinic with diabetes mellitus.

Case Report: Twelve years old boy presented with diabetic ketosis. He had four months long history of polyuria/polydipsia along with 10 kg weight loss. He was the first child of third degree consanguineos parents. He had progressive vision loss due to cone-rod dystrophy. His initial signs were nystagmus and photosensitivity, beginning at six months of age. His height was 154 cm (SDS:0.2), his weight was 45 kg (SDS:-0.05), and his BMI was 18.9 kg/m2 (SDS: -0.48). Pubertal status was compatible with Tanner stage 2. Acanthosis nigricans was noted around the neck and axilla. He had also bilateral nystagmus, kyphoscoliosis and bilateral pes planus. Laboratory examination was compatible with type 2 DM. Serum glucose was 417 mg/dl, and concomitant insulin and c-peptide levels were 24.6 mU/L and 4.76 µg/L, respectively. HbA1c was 13.3% and diabetic autoantibodies were negative. Hypertransaminasemia was also present (ALT: 283 U/L, AST: 229 U/L). Serum lipid profile was normal, except HDL-C level (30 mg/dl). Echocardiographic evaluation was normal. Grade 2 hepatosteatosis was detected with abdominal ultrasonography. Hearing test revealed bilateral mild sensorineural hearing loss. Preliminary diagnosis was Alstrom syndrome with these clinical and laboratory findings. Genetic examination (WES) revealed novel homozygous pathogenic variant [ c.6928dup (p. Thr2310Asnfs*5)] in ALMS1 gene.

Conclusion: Here, we reported a case with Alstrom syndrome with novel pathogenic variant in ALMS1 gene as a rare cause of DM. The clinical manifestations in Alstrom syndrome can be quite variable. Coexistence of type 2 DM, rod-cone dystrophy, sensorinal hearing loss should suggest Alstrom syndrome. Genetic diagnosis is worthwhile as it directs monitoring and treatment of the possible future comorbidities of the syndrome