Table 1.
Summary of Clinical and Molecular Findings in Individuals with De Novo ALDH18A1 Mutations
| Family 1 | Family 2 | Family 3 | Family 4 | Family 5 | Family 6 | Family 7 | Family 8 | Freq. | |
|---|---|---|---|---|---|---|---|---|---|
| Clinical Findings | |||||||||
| Origin | Jordan | Finland | Netherlands | USA | Mexico | UAE | USA | USA | |
| Age at Last Evaluation | 2.5 years | 2.9 years | 2 years | 6 years | 4 years | 13 years | 3 years | 3 years | |
| IUGR | + | + | + | + | + | + | + | + | 100% |
| Postnatal growth delay | + | + | − | + | + | + | + | + | 88% |
| Dysmorphic features | − | + | + | + | + | + | + | + | 88% |
| Lax, wrinkled skin | + | + | + | + | + | + | + | + | 100% |
| Thin, translucent skin | + | + | + | + | + | + | + | + | 100% |
| Joint hyperlaxity | + | + | + | + | + | + | + | + | 100% |
| Hernias | + | + | + | + | − | + | − | + | 100% |
| Hip dislocation | ND | + | − | − | + | + | + | + | 71% |
| Adducted thumb | + | + | − | − | + | + | − | + | 63% |
| Club foot | − | + | − | − | + | + | − | − | 38% |
| Abnormal spine curvature | − | + | − | − | + | + | − | − | 38% |
| Osteopenia | − | + | − | − | + | − | ND | + | 43% |
| Late fontanel closure | − | + | + | − | + | ND | − | + | 50% |
| Wormian bones | ND | + | + | − | − | − | − | − | 29% |
| Microcephaly | + | − | − | + | + | + | + | − | 63% |
| Brain anomalies | − | + | − | − | − | ND | − | − | 14% |
| Cranial vessel tortuosity | − | − | + | + | − | − | + | + | 50% |
| Psychomotor retardation | + | + | + | + | + | + | + | + | 100% |
| Autism | ND | ND | + | − | ND | ND | ND | − | 33% |
| Feeding difficulties | − | + | + | + | ND | ND | + | + | 83% |
| Hypotonia | + | + | + | + | + | ND | + | + | 100% |
| Brisk reflexes | − | + | + | ND | + | ND | − | − | 50% |
| Cataract | − | + | + | + | + | + | + | + | 88% |
| Strabismus | − | − | + | − | − | − | − | + | 25% |
| Additional clinical findings | − | foramen magnum stenosis | foramen magnum stenosis, shallow sella turcica | os odontoideum, disharmonic bone age | − | − | − | − | |
| Plasma amino acid levels | ND | ND | normal | normal | ND | ND | ornithine ↓, arginine ↓, proline ↓ | ornithine ↓, citrulline ↓, proline ↓ | |
| Initial diagnosis | WSS | DBS | DBS | connective tissue disorder | DBS | DBS | cutis laxa | DBS | |
| Molecular Findings | |||||||||
| cDNA | c.412C>T | c.412C>T | c.412C>T | c.413G>T | c.413G>T | c.413G>A | c.413G>A | c.413G>A | |
| Parental origin | paternal | ND | paternal | ND | ND | ND | paternal | ND | |
| Protein | p.Arg138Trp | p.Arg138Trp | p.Arg138Trp | p.Arg138Leu | p.Arg138Leu | p.Arg138Gln | p.Arg138Gln | p.Arg138Gln | |
| MutationTaster score | 0.9999 (DC) | 0.9999 (DC) | 0.9999 (DC) | ||||||
| PolyPhen2 score | 1.000 (PD) | 1.000 (PD) | 1.000 (PD) | ||||||
| SIFT score | 0 (D) | 0.04 (D) | 0.04 (D) | ||||||
Abbreviations and symbols are as follows: +, present; −, absent; ND, not determined; DC, disease causing; PD, probably damaging; D, damaging; Freq, frequency of feature.