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Publication
Rastreio neonatal da homocistinúria clássica revela uma elevada frequência da deficiência em MAT I/III na Península Ibérica
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Advisor(s)
Abstract(s)
A homocistinúria devida à deficiência da enzima cistationina -sintetase ou
“homocistinúria clássica” é uma doença metabólica rara (1/344 000 RN), de
transmissão autossómica recessiva e caracterizada por elevada heterogeneidade
clínica, que frequentemente contribui para o diagnóstico tardio. Existe
tratamento efetivo, se instituído antes de se instalarem sintomas irreversíveis,
pelo que tem sido incluída num número considerável de programas de rastreio
neonatal. O rastreio baseia-se na determinação dos níveis plasmáticos de metionina,
por espectrometria de massa em tandem (ms/ms), mas conduz à identificação
de muitos casos falsos-positivos, portadores de uma condição com
significado clínico não completamente esclarecido, a deficiência em metionina
adenosiltransferase (MAT I/III). Ambas as condições são rastreadas na Galiza e
em Portugal desde 2000 e 2004, respetivamente. Desde então, foram identificados
três doentes com homocistinúria clássica e 44 doentes com deficiência
em MAT I/III. Uma forma dominante, e aparentemente benigna, desta última
condição, associada à mutação p.R264H, parece ser muito frequente na
Península Ibérica. A implementação de um teste de segunda linha, consistindo
na determinação da homocisteína total, permitiria reduzir consideravelmente o
número de RN identificados com deficiência em MAT I/III e melhorar a especificidade
e valor positivo preditivo do rastreio da homocistinúria clássica.
Homocystinuria due to cystathionine -synthase deficiency or “classical homocystinuria” is a rare autosomal recessive condition characterized by high clinical heterogeneity, which contributes to frequent late clinical diagnosis. Treatment is effective if started before irreversible clinical symptoms, which led to its inclusion in a number of newborn screening programs, based on the analysis of methionine levels by tandem mass spectrometry (ms/ms). Nevertheless, false-positive results can be frequently obtained and lead to the unwanted identification of methionine adenosyl transferase (MAT I/III) deficiency, a condition with clinical significance not completely elucidated. Both these metabolic disorders are screened in Galicia and Portugal since the introduction of the ms/ms technology, in 2000 and 2004, respectively, resulting in the identification of three patients with classical homocystinuria and 44 patients with MAT I/III deficiency. A dominant form of MAT I/III deficiency, associated with mutation p.R264H, seems to be very frequent in the Iberian Peninsula and usually is associated with a clinically benign course. The implementation of a second-tier test for homocysteine determination in dried blood spots would considerably reduce the number of MAT I/III-deficient patients identified and improve the specificity and positive predictive value for classical homocystinuria screening.
Homocystinuria due to cystathionine -synthase deficiency or “classical homocystinuria” is a rare autosomal recessive condition characterized by high clinical heterogeneity, which contributes to frequent late clinical diagnosis. Treatment is effective if started before irreversible clinical symptoms, which led to its inclusion in a number of newborn screening programs, based on the analysis of methionine levels by tandem mass spectrometry (ms/ms). Nevertheless, false-positive results can be frequently obtained and lead to the unwanted identification of methionine adenosyl transferase (MAT I/III) deficiency, a condition with clinical significance not completely elucidated. Both these metabolic disorders are screened in Galicia and Portugal since the introduction of the ms/ms technology, in 2000 and 2004, respectively, resulting in the identification of three patients with classical homocystinuria and 44 patients with MAT I/III deficiency. A dominant form of MAT I/III deficiency, associated with mutation p.R264H, seems to be very frequent in the Iberian Peninsula and usually is associated with a clinically benign course. The implementation of a second-tier test for homocysteine determination in dried blood spots would considerably reduce the number of MAT I/III-deficient patients identified and improve the specificity and positive predictive value for classical homocystinuria screening.
Description
Keywords
Doenças Raras Doenças Genéticas Doenças Metabólicas Rastreio Neonatal Homocistinúria Clássica Deficiência em MAT I/III Península Ibérica Galiza Portugal
Pedagogical Context
Citation
Boletim Epidemiológico Observações. 2015;5(Supl 7):21-24
Publisher
Instituto Nacional de Saúde Doutor Ricardo Jorge, IP