RESUMO
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays were developed to measure arylsulfatase A (ARSA) activity in leukocytes and dried blood spots (DBS) using deuterated natural sulfatide substrate. These new assays were highly specific and sensitive. Patients with metachromatic leukodystrophy (MLD) and multiple sulfatase deficiency (MSD) displayed a clear deficit in the enzymatic activity and could be completely distinguished from normal controls. The leukocyte assay reported here will be important for diagnosing MLD and MSD patients and for monitoring the efficacy of therapeutic treatments. ARSA activity was measured in DBS for the first time without an antibody. This new ARSA DBS assay can serve as a second-tier test following the sulfatide measurement in DBS for newborn screening of MLD. This leads to an elimination of most of the false positives identified by the sulfatide assay.
Assuntos
Cerebrosídeo Sulfatase/análise , Teste em Amostras de Sangue Seco , Leucócitos/enzimologia , Leucodistrofia Metacromática/sangue , Doença da Deficiência de Múltiplas Sulfatases/sangue , Cerebrosídeo Sulfatase/metabolismo , Cromatografia Líquida , Humanos , Leucodistrofia Metacromática/diagnóstico , Leucodistrofia Metacromática/enzimologia , Estrutura Molecular , Doença da Deficiência de Múltiplas Sulfatases/diagnóstico , Doença da Deficiência de Múltiplas Sulfatases/enzimologia , Sulfoglicoesfingolipídeos/química , Espectrometria de Massas em TandemRESUMO
BACKGROUND: Multiple sulfatase deficiency is an autosomal recessive lysosomal storage disorder characterized by the absence of several sulfatases and resulting from mutations in the gene encoding the human C (alpha)-formylglycine-generating enzyme. There have been a variety of biochemical and clinical presentations reported in this disorder. PATIENT DESCRIPTION: We present a 4-year-old girl with clinical findings of microcephaly, spondylolisthesis and neurological regression without ichthyosis, coarse facies, and organomegaly. RESULTS: The child's magnetic resonance imaging demonstrated confluent white matter abnormalities involving the periventricular and deep cerebral white matter with the U-fibers relatively spared. Biochemical testing showing low arylsulfatase A levels were initially thought to be consistent with a diagnosis of metachromatic leukodystrophy. The diagnosis of multiple sulfatase deficiency was pursued when genetic testing for metachromatic leukodystrophy was negative. CONCLUSION: This child illustrates the clinical heterogeneity of multiple sulfatase deficiency and that this disorder can occur without the classic clinical features.
