Endocrine Abstracts

Background: Gaucher disease (GD) is the most prevalent lysosomal disorder caused by GBA mutations and abnormal glucocerebrosidase function, leading to glucocerebroside accumulation mainly in the liver, spleen, bone marrow, lungs, and occasionally in the central nervous system. Gaucher disease type 3c (GD3c) is a rare subtype of the subacute/chronic neuronopathic GD3, caused by homozygosity for the GBA p. Asp448His (D409H) mutation.

Case Report: A 24-year-old male patient. He first applied to neurology with the complaint of spasms in the hands and neck. In the evaluation, hepatosplenomegaly and mild pancytopenia were detected. His cytopenia, eye and neurological findings have been present since early childhood. In the family history, his father died at the age of 35 and his brother at the age of 19 due to cardiac reasons. On physical examination, the patient’s vertical eye movements were limited and bradykinesia was detected. In addition, the patient had brown macules scattered on his trunk, diagnosed as tinea versicolor. Bilateral hallux valgus was detected in the orthopedic evaluation. In the complete blood count, the white blood cell count was 3.39x10⁹/l(4.5-11), the hemoglobin level was 8 g/dl(13.2-17.3), and the platelet count was 35x10⁹/l(150-400). In addition, his transferrin saturation was 25%(13-45), total iron binding capacity was 302 mg/dl (250-450), serum iron level was 77 mg/dl(37-145), ferritin level was 987ng/ml(30-400), B12 level was 216 pg/ml(197-771), HDL cholesterol level was 27 mg/dl(40-60). In the MRI volumetric evaluation, the liver volume was 1300cc and the spleen volume was 9959cc. The patient has had no complain of chest pain or exertional dyspnea. In the echocardiographic examination, the aortic and mitral valves were thick. Aortic valve opening was found to be slightly restricted. On MRI of bones, heterogeneous bone marrow intensity was detected in both femur and pelvic bones, there was no osteonecrosis. In bone mineral densitometry, the femoral neck Z score was- 0.2 and the lumbar total Z score was -2.2. Orbital and cranial MRI revealed hydrocephaly, partial empty sella, hyperintense signal foci in T2AG and FLAIR sequences in periventricular and subcortical areas, and thickening in the calvarium. In the psychiatric evaluation, no pathological findings were detected, except for the anxiety. Genetic examination was performed with the preliminary diagnosis of GD. NM-000157.4 c.1342G>C(p.Asp448His) homozygous mutation was detected in the GBA gene compatible with the diagnosis of Gaucher disease type 3c. Thereupon, the patient was started with enzyme replacement treatment as velagluceridase alfa at a dose of 60 U/kg once every 15 days.

Conclusions: Although clinic presentation is variable, heart valve diseases, aortic calcification, oculomator apraxia, abnormal eye movements, corneal opacities, pancytopenia, hepatosplenomegaly, hydrocephalus are the main findings of GD3c.GD3c should definitely be considered in patients with these findings.