| Diagnostic domain | Specimen type(s) | Method | Principal finding / biomarker | Quantitative or technical detail | Example clinical use | Key reference (year; DOI/URL) | Citation |
|---|---|---|---|---|---|---|---|
| Urinary screening | 24 h urine | Thin-layer chromatography after desalting, followed by orcinol staining | Abnormal urinary oligosaccharides / sialylglycopeptides of the O-linked type with Ser/Thr-linked GalNAc | Qualitative TLC pattern; used as initial biochemical screen | Detect characteristic glycopeptiduria in suspected α-NAGA deficiency | Bakker et al. 2001; https://doi.org/10.1038/sj.ejhg.5200598 | (pqac-00000018) |
| Urinary biomarker profiling | Urine | Targeted LC-MS/MS glycomic profiling | Elevated GalNAc-threonine, GalNAc-serine; sometimes hex3-hexNAc3 | GalNAc-threonine Z ≈ 80; GalNAc-serine Z ≈ 20; abnormal oligosaccharide peaks often ≥2 orders of magnitude above negatives | Sensitive modern biochemical detection and differential diagnosis among lysosomal storage disorders | Mak & Cowan 2021; https://doi.org/10.1016/j.ymgme.2021.08.006 | (pqac-00000021, pqac-00000027) |
| Enzyme confirmation | Leukocytes | α-NAGA enzyme activity assay | Markedly reduced or undetectable α-N-acetylgalactosaminidase activity | Profound deficiency reported; no uniform numeric cutoff provided in extracted text | Biochemical confirmation after urine screening | Bakker et al. 2001; https://doi.org/10.1038/sj.ejhg.5200598 | (pqac-00000018) |
| Enzyme confirmation | Cultured skin fibroblasts | α-NAGA enzyme activity assay | Profound fibroblast α-NAGA deficiency | Assays performed in cultured fibroblasts; no numeric activity units captured in extracted text | Confirms diagnosis, especially in atypical cases | Keulemans et al. 1996; https://doi.org/10.1136/jmg.33.6.458 | (pqac-00000022) |
| Cellular storage demonstration | Cultured skin fibroblasts | Lectin histochemistry / immunocytochemical detection | Intralysosomal storage with αGalNAc-reactive material; Tn-antigen accumulation in Kanzaki fibroblasts | Qualitative cellular localization evidence | Supports mechanism and complements enzyme/genetic findings | Keulemans et al. 1996; https://doi.org/10.1136/jmg.33.6.458; Sakuraba et al. 2004; https://doi.org/10.1007/s10038-003-0098-z | (pqac-00000022, pqac-00000012) |
| Blood-based enzymatic testing | Blood | Blood enzyme assay for α-NAGA activity | Diminished α-NAGA activity | Described as enzymatic analysis through a blood test; no extracted numeric threshold | Practical clinical test in case workup | Castro et al. 2019; https://doi.org/10.12890/2019_001269 | (pqac-00000019, pqac-00000020) |
| Molecular confirmation | Leukocyte DNA or fibroblast DNA | PCR amplification and sequencing of NAGA exons/intron boundaries | Pathogenic NAGA variants confirm diagnosis | Nine exons sequenced; example 351-bp PCR fragment for E325K testing, with normal TaqI digestion into 174 and 177 bp fragments abolished by mutation | Gold-standard confirmatory diagnosis; family testing | Bakker et al. 2001; https://doi.org/10.1038/sj.ejhg.5200598 | (pqac-00000018) |
| Molecular confirmation | Blood-derived DNA | PCR / targeted genetic testing | c.577G>T (p.Glu193*) identified in a confirmed case | Variant-level confirmation of Schindler disease | Confirms diagnosis and distinguishes from phenocopies such as Fabry disease | Castro et al. 2019; https://doi.org/10.12890/2019_001269 | (pqac-00000019, pqac-00000020) |
| Broad diagnostic workflow | Plasma, peripheral blood leukocytes, dried blood spots, cultured skin fibroblasts, urine | Stepwise biochemical plus genetic testing | Abnormal biochemical findings should be confirmed by enzymatic assay and targeted/NGS molecular testing | Lab-specific protocols and age-specific reference ranges may vary | Real-world implementation for lysosomal disease workup, including NAGA deficiency | Lange et al. 2024; https://doi.org/10.51847/isa3beaurx | (pqac-00000023) |


*Table: This table summarizes the main diagnostic specimens, methods, and biomarkers reported for Schindler disease / NAGA deficiency. It highlights both classic biochemical workflows and newer LC-MS/MS glycomic profiling findings that support diagnosis and differential testing.*