Table 3.
Undiagnosed patients: reasons for referral and diagnosis
| ID | Reason for referral | IEM diagnosis | OMIM# |
|---|---|---|---|
| 1 | Myopathy, ptosis | Mitochondrial disease (CPEO) | 609,286 |
| 2 | Epilepsy, ophthalmoplegia, ptosis | Mitochondriopathy disease (ARPEO) | 258,450 |
| 3 | Myopathy, arthralgia, cognitive delay | Myoadenylate deaminase deficiency | 615,511 |
| 4 | Myopathy, ovary insufficiency, cognitive decline, palpebral ptosis | Mitochondrial disease (ovario leucodystrophy related to AARS2 variant) | 615,889 |
| 5 | Myopathy, respiratory insufficiency | Heterozygous for Pompe late-onset disease (2nd variant not found) | 232,300 |
| 6 | Myopathy, respiratory insufficiency | Pompe late-onset disease | 232,300 |
| 7 | Myopathy, ophthalmoplegia, ptosis | Mitochondrial disease (CPEO) | 609,286 |
| 8 | Pulmonary embolism | Homocystinuria due to CBS deficiency | 236,200 |
| 9 | Intestinal ischemic thrombosis, pulmonary embolism | Homocystinuria due to CBS deficiency | 236,200 |
| 10 | Myopathy, ptosis | Mitochondrial disease (KSS) | 530,000 |
| 11 | Biochemical hypermethioninemia, cognitive delay | Methionine adenosyltransferase I/III deficiency | 250,850 |
| 12 | Progressive myelopathy | X-linked AMN | 300,100 |
| 13 | Splenomegaly, liver cirrhosis, bone lesions | Niemann-Pick type B | 607,616 |
| 14 | Hypoglycemia, hyperammoniemia | HI/HA syndrome | 606,762 |
| 15 | Positive FHx for OTC | OTC deficiency | 311,250 |
| 16 | Positive FHx for CBS deficiency | Homocystinuria due to CBS deficiency | 236,200 |
| 17 | Positive FHx for CBS deficiency | Homocystinuria due to CBS deficiency | 236,200 |
| 18 | Positive FHx for CBS deficiency | Homocystinuria due to CBS deficiency | 236,200 |
| 19 | Positive FHx for CBS deficiency | Homocystinuria due to CBS deficiency | 236,200 |
| ID | Reason for referral | Other Genetic diagnosis | |
| 20 | Spastic paraparesis, cognitive delay | Spastic paraparesis related to SPG11 variant | 604,360 |
| 21 | Cerebral calcification, leukoencephalopathy | Nasu-Hakola syndrome (PLOSL) | 618,193 |
| 22 | Peripheric weakness, ataxia, ophthalmoplegia | Autosomal dominant spinocerebellar ataxia 5 | 600,224 |
| 23 | Familial neuropathy, muscle weakness | Charcot-Marie Tooth related to LRSAM1 variant | 614,436 |
| 24 | Cognitive decline, peripheric neuropathy, polyglucosan bodies | Charcot-Marie Tooth related to HARS1 variant | 616,625 |
| ID | Reason for referral | Possibly related polymorphisms | |
| 25 | Mild elevation of homocysteine | MTHFR polymorphism (compound heterozygous) | NA |
| 26 | Mild elevation of homocysteine, venous thrombosis | MTHFR polymorphism (compound heterozygous) | NA |
| 27 | Recurrent pregnancy loss | MTHFR polymorphism (compound heterozygous) | NA |
Abbreviations: ARPEO: autosomal recessive progressive external ophalmoplegia; AMN, adrenomyeloneuropathy; CPEO: chronic progressive external ophthalmoplegia; CBS: cystathionine-β synthase deficiency; FHx: family history; HI/HA, hyperinsulinism/hyperammoniemia; ID; identity number, KSS: Kearns-Sayre Syndrome; MTHFR, methylenetetrahydrofolate reductase; NA: not applicable; OMIM: online mendelian inheritance in man; OTC, ornithine transcarbamylase; PLOSL, polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy; X-ALD, X-linked adrenoleucodystrophy