Table 1.
Overview of clinical characteristics of PDE-ALDH7A1 adult patients.
| Case | 1* | 2* | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 |
|---|---|---|---|---|---|---|---|---|---|---|
| Literature | 10, 19–21 | 10, 19–22 | 10, 19–22 | 10, 19–22 | 10, 19–26 | 10, 19–22 | 10, 19–22 | 10, 19–22 | 27 | |
| Gender | Female | Female | Female | Female | Male | Female | Male | Female | Male | Male |
| Mutation analysis | c.1279G>C (pGlu427Gln); c.1279G>C (p.Glu427Gln) | c.1279G>C (pGlu427Gln); c.1279G>C (p.Glu427Gln) | c.1279G>C (pGlu427Gln); c.1279G>C (p.Glu427Gln) | c.1279G>C (pGlu427Gln); c.1279G>C (p.Glu427Gln) | c.1279G>C (pGlu427Gln); c.1279G>C (p.Glu427Gln) | c.834G>A; c.834G>A | c.1279G>C (pGlu427Gln); c.1279G>C (p.Glu427Gln) | c.834G>A; c.1432 T>A (p.Cys478Ser) | c.1279G>C (pGlu427Gln); c.1279G>C (p.Glu427Gln) | c.1483G>A p.(Ala495Thr); c.1483G>A p.(Ala495Thr) |
| Clinical history | prematurity (35 + 6), asphyxia, strabismus | None | Pes planus, scoliosis | Strabismus requiring surgery | Pes planus | Pes planus, vitamin B12 deficiency after gastritis | Premature birth (35 + 5) with asphyxia, metabolic acidosis,liver/kidneyfailure, respiratory insufficiency and lung bleeding. At age six months he had a hydrocephalus requiring ventriculostomy. Strabismus requiring surgery | unilateral cataract, carpal tunnel syndrome, vitamin B12 deficiency, neuralgia back and legs; MRI worn down vertebral discs | At age 5 months he had his first VP-shunt, which was removed two months later because of an infection. At 10y a progressive hydrocephalus was requiring VP-shunt. | possible asphyxia at birth, hypogonadotropic hypogonadism |
| Presentation | ||||||||||
| Seizure onset | 0 d | 2 d | 1 d | 4 d | 9 d | 0 d | 0 d | 5 months | 128 days, after vaccination | 15 d |
| Pyridoxine delay | 4 d | 7 d | 2 d | 3 d | 0d | 116 d | 3 d | 30 days | 9 days | 16 years |
| Treatment | ||||||||||
| Current type of treatment | pyridoxine monotherapy (50 mg) | pyridoxine monotherapy (50 mg) | pyridoxine monotherapy (150 mg) | pyridoxine monotherapy (200 mg) | pyridoxine monotherapy (60 mg) | pyridoxine monotherapy (100 mg) | pyridoxine monotherapy (200 mg) | Pyridoxine (100 mg) + arginine supplementation | pyridoxine monotherapy (200 mg) + risperidone + levetiracetam | pyridoxine 200 mg + valproic acid |
| Neurology | ||||||||||
| age at last follow up | 27.9y | 29.8y | 18y | 19y | 25.2y | 28.5y | 23.3 y | 28.2y | 17.8y | 19.9y |
| Seizure history | breakthrough seizures as a child | breakthrough seizures as a child | no seizures since start pyridoxine | no seizures since start pyridoxine | no seizures since start pyridoxine | no seizures since start pyridoxine | no seizures since start pyridoxine | no seizures since start pyridoxine | unclear, potential abscence-like periods. No fulminant seizures for years | no seizures since start pyridoxine |
| Neurological assessment | Intellectual disability. Cerebral palsy, insecure movements | Problems with longer periods of concentration and automation, delayed processing speed. No motor abnormalities. | Intellectual disability. Mildly abnormal coordination, normal muscle tone | Psychomotor delay, learning disability. No spasticity | No cognitive issues. Walking in straight line sometimes bit wobbly. Tremor both hands, sometimes uncontrollable | Verbally a bit slow, has to think hard | Intellectual disability. Mild dysarthria, divergent eye stand. Abnormal fine motor function. Coordination mildly abnormal. Mild tremor of hands | Normal | Severe intellectual disability and autism. Speaks some single words, and uses sounds for communication. Hands/arms: tremor disturbing eating and drinking. Is able to walk around without major motor abnormalities. Severe autism prevents further formal exam | Intellectual disability. Tremor of hands |
| MRI (age) | corpus callosum anomaly, cortical injury of sulcus centralis, left ventriculomegaly, white matter abnormalities (8y) | white matter abnormalities (16y) | corpus callosum anomaly, white matter abnormalities (11y) | corpus callosum anomaly, hyperintensity globus pallidus, ventriculomegaly (0.5y) | corpus callosum anomaly, mega cisterna magna, ventriculomegaly (12y) | normal (0.5y) | third ventriculostomy, 1y corpus callosum anomaly, left cerebellar and caudal vermis hypoplasia, ventriculomegaly (0.5y) | normal (15y) | CT cyst fourth ventricle. Ventriculomegaly after VP shunt was removed (0.8y) | changes due to prolonged seizures, possibly reflecting meningitis (16y) |
| Neurodevelopment | ||||||||||
| Last formal neurodev test (age) | WPPSI (12.5y) | WISC-R (12.5y) | WISC-III (12y) | Son-R (5y) | WISC-III (12.5y) | WISC-III (17y) | SON-R (7y) | WISC-III (17y) | unknown | Weschler non verbal (15y) |
| FSIQ (VIQ; PIQ) | Developmental age 5.5-6y. Verbal 7y. Previous IQ <50 (9y) | 77(80;78) | 53 (unk;unk) | IQ <50, reference age of 2y | 106 (114;96) | 71 (72;76) | developmental level of 3:10y | 86 (91;84) | IQ < 50 | 55 |
| Behavioral abnormalities | Autistic traits | None | None | None | None | None | None | None | severe autism | Behavioral problems (not specified), concentration problems, not adequately responding to answers |
| Highest educational level | Lower | intermediate | Lower | Lower | tertiary | intermediate | Lower | intermediate | never followed regular education or obtained an educational level | Lower |
| Occupation | Social day care | Maintains a job without assistance | Social day care; job with assistance | Job with assistance | In university | Maintains a job without assistance | Job with assistance | Maintains a job without assistance | Social day care | Job with assistance |
| General comments | siblings | siblings | Older sibling (brother) died in the first week of life due to an unexplained incident necessitating resuscitation. | refugee, medical history from before age 14y limited | ||||||
| PROMIS | ||||||||||
| Age PROMs | 28.1y | 30y | 18.2y | 19.6y | 25.7y | 28.5y | 23.3y | 28.5y | 18y | 19.9y |
| completed by who | parent | self | parent | parent | self | Together with parent | parent | self | parent | Parent with social worker |
*= siblings, CT = computed tomography, FSIQ = full-scale intelligence quotient, MRI = magnetic resonance imaging, mg = milligram, PIQ = performance IQ, PROMs = patient-reported outcomes measurements, PROMIS = Patient-reported Outcomes Measurement Instruments System, VIQ = verbal IQ, y = year.