Table A5.
Isovaleric acidaemia (IVA), 8.5 points.
| Condition (2.5 out of 6 Points) | Screening (3 out of 3 Points) | Treatment (3 out of 4 Points) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Severity | The disorder only has severe forms | 0 | AND | Availability | DBS test is available and in use | 2 | OR | Availability | An EMA-approved treatment is available | 0 | OR |
| There is a rapidly progressing form | 0.5 | DBS test is not yet available, but is in development with published evidence | 0 | A treatment intervention is available (diet, HSCT, BMT) | 1 | ||||||
| The disorder can be fatal by adolescence | 1 | Performance | DBS test has a low false-positive rate and/or a high PPV | 1 | OR | A treatment is in late development (phase 3) | 0 | ||||
| Onset | All forms of the disorder are asymptomatic for the first few weeks of life | 0 | AND | DBS test has a high false-positive rate and/or a low PPV and/or requires additional confirmatory strategies that are available to improve screening performance | 0 | A treatment is in early development (preclinical, phase 1, or phase 2) | 0 | ||||
| More than 50% of cases are an early-onset phenotype | 0 | Outcomes | The treatment strategy changes the prognosis for all forms of the disorder | 0 | OR | ||||||
| Frequency | Greater than or equal to 1 in 50,000 | 0 | OR | The treatment strategy changes the prognosis for some forms of the disorder | 1 | ||||||
| Greater than or equal to 1 in 100,000 and less than 1 in 50,000 | 0 | The treatment strategy does not change prognosis or improves only some symptoms of the disorder | 0 | ||||||||
| Greater than or equal to 1 in 150,000 and less than 1 in 100,000 | 1 | Pre-symptomatic initiation results in better outcomes | 1 | AND | |||||||
| Between 1 in 250,000 and 1 in 150,000 | 0 | ||||||||||