Hyperammonaemia

Gene: SERAC1

Green List (high evidence)

Comment on publications: Added publications to support the phenotype

Created: 19 Dec 2017, 11:44 a.m.

Comment on phenotypes: Added phenotype

Created: 19 Dec 2017, 11:43 a.m.

Comment on mode of inheritance: added MOI from expert review

Created: 19 Dec 2017, 11:43 a.m.

Comment on list classification: changed form Red to to Green due to evidence in the literature

Created: 19 Dec 2017, 11:43 a.m.

Added from Intellectual disability panel update as gene is also relevant to this panel

Created: 19 Dec 2017, 11:42 a.m.

Wortmann et al (2017) PMID: 29205472 reclassified MEGDEL syndrome to MEGDHEL syndrome, 3-MEthylGlutaconic aciduria, Dystonia-Deafness, Hepatopathy, Encephalopathy, Leigh-like syndrome (MEGDHEL) as they found that liver involvement was an additional clinical feature, so Hepatopathy was incorporated into the acronym. From a study of 67 individuals (39 previously unreported) from 59 families were included (age range 5 days - 33.4 years, median age 9 years) Wortmann et al idenitified 41 different SERAC1 biallelic variants, including 20 that have not been reported before. With exception of two families with a milder phenotype, all affected individuals show a strikingly homogeneous phenotype and time course. Severe, reversible neonatal liver dysfunction and hypoglycemia was seen in more than 40% of all cases. Starting at a median age of six months muscular hypotonia (91%) was seen, followed by progressive spasticity (82%, median onset 15 months) and dystonia (82%, 18 months). The majority of affected individuals never learnt to walk (68%). 79% suffered hearing loss, 58% never learnt to speak, nearly all had significant intellectual disability (88%).

Created: 19 Dec 2017, 11:40 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, 614739; MEGDEL syndrome; 3-MEthylGlutaconic aciduria, Dystonia-Deafness, Hepatopathy, Encephalopathy, Leigh-like syndrome; MEGDHEL syndrome

Publications

• 29205472
• 22683713
• 16527507
• 28482397
• 28778788
• 27186703
• 27604308

Red List (low evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
3-Methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndromeMEGD(H)EL

Please note that phenotypes that already existed for this gene panel (viewed under Gene Summary) and Ensembl transcripts were accidently uploaded under Peter Clayton (UCL Institute of Child Health)'s review and were not suggested by him. We are working on a fix in PanelApp to correct this.

Created: 5 Nov 2015, 5:19 p.m.