Gaucher Disease: Report about Two Cases with Mild Mutations and Severe Clinical Disease and the Response Using Enzyme Replacement Therapy.
Authors: Aranda Paulo C. , Rozenberg Roberto 
Published: October 2019

Abstract
INTRODUCTION:
Gaucher Disease is the most common genetic lysosomal storage disease due to autosomal recessive mutations in the gene encoding glucocerebrosidase enzyme, which cause a deficient enzyme activity, involving heterogeneous signs and symptoms, like hepatomegaly, splenomegaly, thrombocytopenia, bleeding trend, anemia, bone disease, pulmonary disease, acute or cronic CNS disease (Gaucher Disease types I, II or III). We discuss two patients, sisters, whose father and mother are cousins, who have a mild genetic mutation, but severe systemic and moderate CNS disease, the treatment using Enzyme Replacement Therapy and the good response for it.
CLINICAL PRESENTATION:
– J.O.N, female, eleven years old, diagnosed in february 2003, presenting anemia, severe hepatosplenomegaly, bone disease, growth retardation, mild cognitive deficit, strabismus, important gait disturbance. – Peripheral blood: red cels=3,53, hemoglobin=7,9, hematocrit 25,7%, leucocytes=3.800, platelets=36.000 – Beta glucosidase level = 1,34 nmol/h/mg protein (n= 10 – 45) – Chitotriosidase level = 58.582 nmol/h/mg protein (n= 8,85 – 132) – Mutation: L444P/G377S – S.L.N, female, four years old, diagnosed in February 2003, presenting anemia, moderate hepatosplenomegaly, bone disease, growth retardation, mild cognitive deficit, strabismus, gait disturbance. – Pheriferal blood: red cels=4,22, hemoglobin=9,1, hematocrit=27,2% – Leucocytes=6.200, platelets=54.000 – Beta glucosidase level = 0,67 nmol/h/mg protein (n= 10 – 45) – Chitotriosidase level = 30.002 nmol/h/mg protein (n= 8,85 – 132) – Mutation: L444P/G377S
TREATMENT AND RESULTS:
Both patients started the enzyme replacement therapy using imiglucerase, 60 UI/KG every other week in june 2003. Fastly we observed the hepatosplenomegaly reduction, increase in pheriferal blood cells, the gait disturbance was disappearing (patient S.L.N is walking by herself and J.O.N is walking using walking-stick or when someone help her), the bone disease and the cognitive deficit are less marked and they are growing.
COMMENTS:
– The mutation G377S are expected to cause a type 1 phenotype, even in compound heterozigosity with a second mutation (in these cases L444P) or a null allele; in these cases we observed a Gaucher Disease type III; – The mild mutation G377S causes a high residual activity of Beta-glucosidase enzyme (17,6%), but in our experience, it was not, just by itself, a CNS protector; – We observed a very good response to Enzyme Replacement Therapy in the systemic disease using Imiglucerase 60 UI/Kg every other week. We could see a increase in neurological functions too. May be a mild mutation G377S, due the residual Beta glucosidase activity “helped” the ERT in these cases. – The genotyping Gaucher Disease patients may be critical to improve genotype-phenotype correlations, to offer genetic counseling to carrier couples and in some cases even for therapeutic decision making.
PERIPHERAL BLOOD PATIENT - J.O.N. (BEFORE E.R.T. FEB/2003) PATIENT - J.O.N. (AFTER 24 MONTHS E.R.T. JUNE/2005) PATIENT - S.L.N. (BEFORE E.R.T. FEB/2003) PATIENT - S.L.N. (AFTER 24 MONTHS E.R.T. JUNE/2005) RED CELLS 3,53 millions/mm3 4,60 millions/mm3 4,22 millions/mm3 4,94 millions/mm3 HEMOGLOBIN 7,9 g/% 13,1 g/% 9,1 g/% 13,3 g/% HEMATOCRIT 25,7 % 38 % 27,2 % 40 % LEUCOCYTES 3.800/mm3 7.300/mm3 6.200/mm3 5.100/mm3 PLATELETS 36.000/mm3 304.000/mm3 54.000/mm3 201.000/mm3