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| Miscellaneous Metabolic Disorders v1.28 | ALDOB |
Zornitza Stark gene: ALDOB was added gene: ALDOB was added to Miscellaneous Metabolic Disorders. Sources: Expert Review Mode of inheritance for gene: ALDOB was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ALDOB were set to Fructose intolerance, hereditary, MIM# 229600 Review for gene: ALDOB was set to GREEN Added comment: Well established gene-disease association. Clinical symptoms of HFI include gastrointestinal distress (nausea, vomiting, diarrhea, abdominal pain, anorexia), jaundice, bleeding tendency, renal tubular dysfunction and metabolic disturbances following dietary exposure to fructose, sucrose, or sorbitol. If large quantities of fructose are ingested, lethargy, seizures, and/or progressive coma may ensue. Persistent fructose exposure can result in chronic growth restriction, failure to thrive, renal and hepatic failure, and risk of death. Symptoms appear in infancy at the time of weaning. Treatment: Lifelong dietary restriction of fructose, sucrose, and sorbitol. Assessed as 'strong actionability' by ClinGen. Of particular note, a 24% sucrose solution (routinely administered to hospitalized neonates for minor procedures) should not be given to neonates known to have HFI. This recommendation is supported by case reports of reported accidental and iatrogenic fructose infusion-related serious organ failure events and/or deaths. Alerts should be placed in the patient's chart or medical record to notify practitioners to the HFI diagnosis and to the medical risks associated with exposures to fructose and related metabolites. The patient is advised to wear at all times a medically approved alert bracelet/necklace that provides information about the diagnosis of HFI. Evidence from 50 patients presenting with confirmed and symptomatic HFI shows that upon dietary restriction of fructose, the improvement observed is dramatic: vomiting and gastrointestinal symptoms resolved nearly immediately, bleeding tendency resolves in ~24 hours, renal tubular dysfunction can resolve in as little as 3 days, and clinical and biological findings, with the exception of hepatomegaly, resolved within a few weeks. Normal growth occurred in 2-3 years. In the 50 symptomatic patients and 5 patients who received treatment from birth, liver enlargement persisted in spite of treatment and resolution of fibrosis. Sources: Expert Review |
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| Miscellaneous Metabolic Disorders v1.9 | HIBADH |
Alison Yeung gene: HIBADH was added gene: HIBADH was added to Miscellaneous Metabolic Disorders. Sources: Literature Mode of inheritance for gene: HIBADH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HIBADH were set to 34176136 Phenotypes for gene: HIBADH were set to organic aciduria Review for gene: HIBADH was set to RED Added comment: Single family reported with two siblings presenting with 3-Hydroxyisobutyric aciduria. Male sib with neurodevelopmental symptoms, female sibling asymptomatic. No functional studies Sources: Literature |
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| Miscellaneous Metabolic Disorders v1.4 | SLC10A1 |
Zornitza Stark gene: SLC10A1 was added gene: SLC10A1 was added to Miscellaneous Metabolic Disorders. Sources: Expert list Mode of inheritance for gene: SLC10A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC10A1 were set to 24867799; 27882152; 28835676; 29290974; 31201272 Phenotypes for gene: SLC10A1 were set to Familial hypercholanemia-2, MIM#619256 Review for gene: SLC10A1 was set to GREEN Added comment: IEM characterised by persistently increased plasma levels of conjugated bile salts apparent from infancy. Most patients are asymptomatic and have no liver dysfunction, although some neonates may have transient jaundice or transiently elevated liver enzymes. These abnormalities improve with age. The bile acid defect can result in impaired absorption of fat-soluble vitamins, including D and K, causing decreased bone mineral density or prolonged prothrobin time (PT). Some variants are recurrent (founder effect likely) but at least 3 different variants reported, mouse model. Sources: Expert list |
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| Miscellaneous Metabolic Disorders v0.332 | CD320 |
Bryony Thompson gene: CD320 was added gene: CD320 was added to Miscellaneous Metabolic Disorders. Sources: Literature Mode of inheritance for gene: CD320 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CD320 were set to 29663633; 27604308; 30303736 Phenotypes for gene: CD320 were set to Methylmalonic aciduria, transient, due to transcobalamin receptor defect MIM#613646; Disorders of cobalamin absorption, transport and metabolism Review for gene: CD320 was set to GREEN Added comment: At least 9 cases reported with biallelic variants, all but 1 case are homozygous for p.Glu88del. The AF of this variant is ~1% in gnomAD v2.1.1, with 12 homozygotes. However, this is not unexpected given the apparent asymptomatic nature of the metabolic condition. Null mouse model has vitamin B12 deficiency. Sources: Literature |
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| Miscellaneous Metabolic Disorders v0.231 | SLC30A10 |
Zornitza Stark gene: SLC30A10 was added gene: SLC30A10 was added to Miscellaneous Metabolic Disorders. Sources: Expert list Mode of inheritance for gene: SLC30A10 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC30A10 were set to 22341972 Phenotypes for gene: SLC30A10 were set to Hypermanganesemia with dystonia 1, MIM# 613280 Review for gene: SLC30A10 was set to GREEN Added comment: Hypermanganesemia with dystonia-1 (HMNDYT1) is an autosomal recessive metabolic disorder characterized by increased serum manganese, motor neurodegeneration with extrapyramidal features, polycythemia, and hepatic dysfunction, which leads to cirrhosis in some cases. Intellectual function is preserved. More than 5 unrelated families reported. Sources: Expert list |
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| Miscellaneous Metabolic Disorders v0.107 | ABCB4 |
Bryony Thompson gene: ABCB4 was added gene: ABCB4 was added to Miscellaneous Metabolic Disorders. Sources: NHS GMS Mode of inheritance for gene: ABCB4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ABCB4 were set to 8666348 Phenotypes for gene: ABCB4 were set to Cholestasis, progressive familial intrahepatic 3 MIM#602347; disorder of bile acid metabolism Review for gene: ABCB4 was set to GREEN gene: ABCB4 was marked as current diagnostic Added comment: Well-established gene-disease association (see OMIM entry). PFIC3 is classified as a metabolic disorder by the NIH GARD (https://rarediseases.info.nih.gov/diseases/diseases-by-category/14/metabolic-disorders). ABCB4 deficiency causes an inborn error of bile acid biosynthesis. Sources: NHS GMS |
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| Miscellaneous Metabolic Disorders v0.105 | ABCB11 |
Bryony Thompson gene: ABCB11 was added gene: ABCB11 was added to Miscellaneous Metabolic Disorders. Sources: NHS GMS Mode of inheritance for gene: ABCB11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ABCB11 were set to 9806540 Phenotypes for gene: ABCB11 were set to Cholestasis, progressive familial intrahepatic 2 MIM#601847; disorder of bile acid metabolism Review for gene: ABCB11 was set to GREEN gene: ABCB11 was marked as current diagnostic Added comment: Well-established gene-disease association (see OMIM entry). PFIC2 is classified as a metabolic disorder by the NIH GARD (https://rarediseases.info.nih.gov/diseases/diseases-by-category/14/metabolic-disorders). ABCB11 deficiency causes an inborn error of bile acid biosynthesis. Sources: NHS GMS |
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| Miscellaneous Metabolic Disorders v0.101 | ATP8B1 |
Bryony Thompson gene: ATP8B1 was added gene: ATP8B1 was added to Miscellaneous Metabolic Disorders. Sources: NHS GMS Mode of inheritance for gene: ATP8B1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATP8B1 were set to 9500542 Phenotypes for gene: ATP8B1 were set to Cholestasis, progressive familial intrahepatic 1 MIM#211600; disorder of bile acid metabolism Review for gene: ATP8B1 was set to GREEN Added comment: Well-established gene-disease association (see OMIM entry). ATP8B1 deficiency can cause bile acid synthesis defects. Sources: NHS GMS |
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| Miscellaneous Metabolic Disorders v0.89 | ATIC | Bryony Thompson Marked gene: ATIC as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Miscellaneous Metabolic Disorders v0.89 | ATIC | Bryony Thompson Gene: atic has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Miscellaneous Metabolic Disorders v0.89 | ATIC | Bryony Thompson Classified gene: ATIC as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Miscellaneous Metabolic Disorders v0.89 | ATIC | Bryony Thompson Gene: atic has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Miscellaneous Metabolic Disorders v0.88 | ATIC |
Bryony Thompson gene: ATIC was added gene: ATIC was added to Miscellaneous Metabolic Disorders. Sources: NHS GMS Mode of inheritance for gene: ATIC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATIC were set to 15114530; 32557644 Phenotypes for gene: ATIC were set to AICA-ribosiduria due to ATIC deficiency MIM#608688; disorders of purine metabolism Review for gene: ATIC was set to GREEN Added comment: 4 cases from 3 independent families. Deficiency causes an inborn error of purine metabolism. Sources: NHS GMS |
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| Miscellaneous Metabolic Disorders v0.20 | ADSL |
Bryony Thompson gene: ADSL was added gene: ADSL was added to Miscellaneous Metabolic Disorders. Sources: NHS GMS Mode of inheritance for gene: ADSL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADSL were set to 1302001; 22180458; 18524658; 27626380 Phenotypes for gene: ADSL were set to Adenylosuccinase deficiency MIM#103050 Review for gene: ADSL was set to GREEN gene: ADSL was marked as current diagnostic Added comment: Adenylosuccinase deficiency is an autosomal recessive inborn error of purine metabolism caused by an enzymatic defect in de novo purine synthesis (DNPS) pathway. Well-established gene-disease association (see OMIM). Knockout mouse model is homozygous lethal. Sources: NHS GMS |
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| Miscellaneous Metabolic Disorders v0.12 | ACAD8 |
Bryony Thompson gene: ACAD8 was added gene: ACAD8 was added to Miscellaneous Metabolic Disorders. Sources: NHS GMS Mode of inheritance for gene: ACAD8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACAD8 were set to 12359132; 17304052 Phenotypes for gene: ACAD8 were set to Isobutyryl-CoA dehydrogenase deficiency MIM#611283 Review for gene: ACAD8 was set to GREEN gene: ACAD8 was marked as current diagnostic Added comment: Inborn error of valine metabolism. Isobutyryl-CoA dehydrogenase deficiency was identified in at least 9 cases in 8 families, 6 of the cases were asymptomatic at the time of the study. Sources: NHS GMS |
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