Patient care in Brazil: opportunities and challenges Soraia Poloni, RD, PhD Researcher, Medical Genetics Service Hospital de Clínicas de Porto Alegre Brazil

Brazil >200 million inhabitants 8.515.767,049 km2 Heterogeneous genetic and cultural background

Challenges Diagnosis Treatment Surveillance

Classical homocystinuria (HCU) epidemiology Prevalence worldwide: 1:200,000 So at least 500 HCU patients would be expected in Brazil Ireland 1:65.000 Qatar 1:1.800 Norway 1:6.400 Tao tribe (Taiwan) 1:240 Germany 1:17.800 Denmark 1:20.500 Georgia (USA) 1:351.000

Between 2012-2016 we investigated the clinical and molecular profile of Classical Homocystinuria (HCU) in Brazil.

Subjects included 66 patients 57 non-related families 15 health centers 1 4 Clinical data + DNA: n=35 Clinical data, no DNA: n=6 Only clinical data at diagnosis, no DNA: n=26 4 1 4 1 35 2 2 12

Sample features Consanguinity: 57% of the families Age: median 19 years (min:4; max: 45 years) Sex: 59% were male. 82%

Clinical suspicion + biochemical findings Diagnosis Family screening n=10 Clinical suspicion + biochemical findings n=56

First symptom reported: Ectopia lentis: 35% of the patients Non-specified visual impairment: 23% Developmental delay: 20% Seizures: 12%

Diagnosis Reasons for clinical suspicion of HCU At the time of diagnosis, 40% of the patients had at least three symptoms of HCU! *Including stroke. **Including marfanoid habitus.

Diagnosis Clinical picture at the time of diagnosis CNS: central nervous system

Median age at first symptom Median age at diagnosis The path to diagnosis... Birth 4 years 10 years Median age at first symptom Median age at diagnosis

Management

Results and Discussion Management 28% of patients had total homocysteine levels <60 µmol/L. Treatment adherence was reported in 44% of patients (71% of those responsive and 41% of those nonresponsive). Treatment strategies: 89% on folic acid + pyridoxine 76% on betaine 32% on vitamin B12 26% on a low-methionine diet + metabolic formula Nonresponsive only: 87% were on betaine and 33% on low-methionine diet + metabolic formula.

Analysis of mutations Most prevalent mutations: p.Ile278Thr (allele frequency 18.2%) B6 + p.Thr191Met (allele frequency 11.3%) B6 - c.828+1G>A (allele frequency 11.3%) B6 ? P.Trp323Ter (allele frequency 11.3%) B6 ?

Health team Patients* had regular follow up with... *Data reported for 26 patients

In summary... Most patients described in our study express a severe phenotype, associated with nonresponsiveness to pyridoxine, early and multisystem manifestations, and poor metabolic control. We believe responsive patients were underrepresented in this sample as a result of underdiagnosis of the milder forms of HCU. The poor compliance to the methionine-restricted diet and frequent prescription of betaine among pyridoxine nonresponsive patients suggests difficulties in prescription and adherence to diet.

Late and under -diagnosis Limited and heterogeneous access to health care services and treatment Poor metabolic control Medical expertise Challenges Patients/health care professionals network across the country. Development of protocols and guidelines for better diagnosis and management of HCU in Brazil. Support for public policies. Better knowledge of clinical picture and genetic basis of HCU in Brazil Opportunities

Thank you! soraiapoloni@yahoo.com.br First Brazilian Meeting for Patients with Homocystinuria Porto Alegre, 2016 Thank you! soraiapoloni@yahoo.com.br