| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Additional findings_Adult v1.21 | ASS1 |
Zornitza Stark gene: ASS1 was added gene: ASS1 was added to Additional findings_Adult. Sources: Literature Mode of inheritance for gene: ASS1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ASS1 were set to Citrullinemia MIM#215700 Review for gene: ASS1 was set to GREEN Added comment: Approximately 1/3 of individuals present with late onset. Hyperammonaemia can be triggered by protein overload, catabolic events (including pregnancy), or certain drugs and can lead to neurological deficits. Liver failure is now recognized as a primary presentation. Hepatic dysfunction, when present, is often noted at the time of initial hyperammonaemic episode but has also developed in individuals not experiencing significant hyperammonemia. The mainstay of long-term management is dietary treatment based on minimizing the nitrogen load on the urea cycle under the expertise of a specialist metabolic dietician; may also include nitrogen scavengers. Elective surgery should be performed in centers with a metabolic department including emergency treatment options for hyperammonaemia. Steroids and valproate contraindicated. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Additional findings_Adult v1.19 | CPS1 |
Zornitza Stark gene: CPS1 was added gene: CPS1 was added to Additional findings_Adult. Sources: Expert list Mode of inheritance for gene: CPS1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CPS1 were set to Carbamoylphosphate synthetase I deficiency MIM#237300 Review for gene: CPS1 was set to GREEN Added comment: Can rarely present in adulthood, including in the postpartum period with coma. ACMG factsheet relating to management of adults: https://www.acmg.net/PDFLibrary/CPS-I-Deficiency-Transition.pdf. Management aims to maintain stable metabolic control and to reduce or eliminate chronic complications. Treatment includes medications to promote waste nitrogen excretion (nitrogen scavengers such as sodium benzoate, sodium phenylacetate, sodium phenylbutyrate, and glycerol phenylbutyrate); low-protein diet; and supplementation with arginine or citrulline, essential nutrients, and essential amino acids. Given the risk of acute metabolic decompensation during surgery and general anaesthesia, elective surgery should only be carried out in centers able and prepared to deal with hyperammonemic decompensations. Specialised management is also required during pregnancy. Steroids and valproate are to be avoided. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Additional findings_Adult v1.9 | SLC25A15 |
Zornitza Stark gene: SLC25A15 was added gene: SLC25A15 was added to Additional findings_Adult. Sources: Expert list Mode of inheritance for gene: SLC25A15 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SLC25A15 were set to Hyperornithinaemia-hyperammonaemia-homocitrullinaemia syndrome , MIM#238970 Review for gene: SLC25A15 was set to GREEN Added comment: Approximately one third of individuals present in adolescence/adulthood. Long-term management aims to maintain stable metabolic control, to reduce chronic complications, and to achieve as close to normal development and growth as possible. A low protein diet and citrulline or arginine supplementation is recommended, which prevents hyperammonemia and liver disease but the impact of these measures on pyramidal dysfunction is unclear. Optimal protein intake must be determined by individual titration in every individual. If protein tolerance is very low, essential amino acids have to be supplemented. Vitamin and trace element supplementation may also be required. A specialist metabolic dietitian should be involved. Nitrogen scavengers (sodium benzoate, sodium phenylbutyrate [PBA] or sodium phenylacetate, glycerol phenylbutyrate) are a mainstay of therapy in individuals with a UCD. Individualized dosing is recommended. Presentation can be non-specific and diagnostic delay is common. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Additional findings_Adult v1.5 | SLC25A13 |
Zornitza Stark gene: SLC25A13 was added gene: SLC25A13 was added to Additional findings_Adult. Sources: Expert list Mode of inheritance for gene: SLC25A13 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SLC25A13 were set to Citrullinaemia, adult-onset type II, MIM# 603471 Review for gene: SLC25A13 was set to GREEN Added comment: CTLN2 typically presents in childhood but presents with hyperammonaemia in adolescence or adulthood. Presentation is sudden and usually between ages 20 and 50 years. Misdiagnosis and delayed diagnosis in adults is common. Possible interventions include liver transplantation and/or dietary therapy, ongoing blood monitoring, and avoidance of possible triggers (e.g., medications and alcohol). Individuals with UCDs require lifelong monitoring by a multidisciplinary team. Long-term treatment of UCDs is challenging for individuals and families because of the poor palatability (particularly of essential amino acids), the volume and frequency of diet and drug administrations. Nasogastric tube or gastrostomy feeding may be necessary to ensure sufficient energy and/or protein intake. Sodium pyruvate is administered orally as a powder, granules, capsules, tablets, or liquid. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Additional findings_Adult v0.144 | ENG | Zornitza Stark Marked gene: ENG as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Additional findings_Adult v0.144 | ENG | Zornitza Stark Gene: eng has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Additional findings_Adult v0.144 | ENG | Zornitza Stark Classified gene: ENG as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Additional findings_Adult v0.144 | ENG | Zornitza Stark Gene: eng has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Additional findings_Adult v0.143 | ENG |
Zornitza Stark gene: ENG was added gene: ENG was added to Additional findings_Adult. Sources: Expert list Mode of inheritance for gene: ENG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ENG were set to 34012068 Phenotypes for gene: ENG were set to Telangiectasia, hereditary hemorrhagic, type 1, MIM# 187300 Review for gene: ENG was set to GREEN Added comment: Included in ACMG V3.0 SF list, potential morbidity meets penetrance threshold and has effective intervention. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||