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

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

3. Challenges
Diagnosis
Treatment
Surveillance

4. 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:

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

6. 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

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

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

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

10. 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.

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

12. 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

13. Management

14. 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.

15. 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 ?

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

17. 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.

18. 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

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