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Zpráva o onemocněních · Metabolic

Urea Cycle Disorders

Whole genome sequencing evaluates all urea cycle genes (OTC, CPS1, ASS1, ASL, ARG1, NAGS) and distinguishes X-linked OTC deficiency from autosomal recessive defects, enabling accurate genetic counseling and family screening.

Zpráva o onemocněních hledá vzácné varianty, o nichž je známo, že způsobují onemocnění, na něž se zpráva zaměřuje.

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O tomto condition

A genetic inborn error of metabolism characterized by the deficiency of one of the enzymes necessary for the urea cycle. It results in accumulation of ammonia in the body.

Urea cycle defects (UCDs) are a group of inherited metabolic disorders caused by deficiency of enzymes or transporters in the urea cycle, the hepatic pathway that converts neurotoxic ammonia to urea for renal excretion. Six primary UCDs are recognized: ornithine transcarbamylase (OTC) deficiency (X-linked, most common, ~50% of all UCDs), carbamoyl phosphate synthetase I (CPS1) deficiency, argininosuccinate synthetase (ASS1) deficiency (citrullinemia type I), argininosuccinate lyase (ASL) deficiency, arginase (ARG1) deficiency, and N-acetylglutamate synthase (NAGS) deficiency. Combined incidence is approximately 1 in 30,000-35,000 births.

UCDs present with hyperammonemia: elevated blood ammonia that is directly neurotoxic. Severe neonatal-onset forms (typically OTC, CPS1, or ASS1 in males with complete enzyme deficiency) present within the first days of life with progressive lethargy, poor feeding, vomiting, hypothermia, and rapid progression to coma and death if untreated. Late-onset forms present with recurrent episodes of hyperammonemia triggered by catabolic stress (illness, surgery, high-protein intake, postpartum period), which can cause encephalopathy, cerebral edema, and progressive cognitive impairment with each episode.

Management includes dietary protein restriction, nitrogen scavenger therapy (sodium benzoate and/or sodium phenylbutyrate/glycerol phenylbutyrate, which provide alternative pathways for nitrogen excretion), essential amino acid supplementation, and emergency hyperammonemia protocols. Liver transplantation is curative for hepatic UCDs (OTC, CPS1, ASS1, NAGS) because the urea cycle is exclusively hepatic; a transplanted liver provides functional enzyme. mRNA therapy delivering functional OTC mRNA to hepatocytes is in clinical trials for OTC deficiency, potentially offering a non-surgical alternative to liver transplantation.

OTC deficiency is X-linked: affected males typically present in the neonatal period, but carrier females can present at any age, often triggered by catabolic stress (illness, surgery, postpartum). Postpartum hyperammonemia in a previously healthy woman should prompt OTC carrier testing.

Všech 2 onemocnění, která analyzujeme

Urea Cycle Disorder

A genetic inborn error of metabolism characterized by the deficiency of one of the enzymes necessary for the urea cycle. It results in accumulation of ammonia in the body.

Co se diagnózou změní

Nitrogen scavenger therapy (sodium benzoate, glycerol phenylbutyrate/Ravicti); protein-restricted diet with essential amino acid supplementation; emergency hyperammonemia protocols; liver transplantation (curative); mRNA therapy trials for OTC; carglumic acid for NAGS deficiency

Analyzované geny

Známé také jako

disorder of urea cycle metabolism; inborn disorder of urea cycle metabolism and ammonia detoxification; inborn urea cycle disorder; UCD; urea cycle metabolism disorder

Zahrnuje 18 příbuzných podtypů ↓
  • 3-methylcrotonyl-CoA carboxylase 1 deficiency
  • acute neonatal citrullinemia type I
  • adult-onset citrullinemia type I
  • arginase deficiency
  • argininosuccinic aciduria
  • carbamoyl phosphate synthetase I deficiency disease
  • citrin deficiency
  • citrullinemia
  • citrullinemia type I
  • citrullinemia type II
  • citrullinemia, type II, adult-onset
  • hyperammonemia due to N-acetylglutamate synthase deficiency
  • hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency
  • hyperinsulinism-hyperammonemia syndrome
  • neonatal intrahepatic cholestasis due to citrin deficiency
  • ornithine carbamoyltransferase deficiency
  • ornithine translocase deficiency
  • urea cycle disorder or inherited hyperammonemia
MONDO:0004739Orphanet 79167MedGen 57586

Lysinuric Protein Intolerance

Autozomálně recesivní

Caused by variants in SLC7A7, which impair transport of lysine, arginine and ornithine and can cause high ammonia after protein-rich meals, poor growth, lung and kidney complications.

Co se diagnózou změní

Knowing allows protein restriction and citrulline supplementation, managed like a urea cycle disorder, with monitoring of lungs and kidneys.

Analyzované geny

Známé také jako

dibasic aminoaciduria 2; Dibasicamino aciduria II; hyperdibasic aminoaciduria; hyperdibasic aminoaciduria type 2; LPI

MONDO:0009109OMIM 222700Orphanet 470MedGen 75704

Proč sekvenování celého genomu

OTC deficiency is X-linked; other UCDs are autosomal recessive. The inheritance pattern has profound implications for family screening, prenatal diagnosis, and recurrence risk; only molecular diagnosis reliably determines the specific UCD.

Hyperammonemia kills neurons in hours: emergency protocols require knowing the specific UCD for optimal management

Each UCD has a specific biochemical profile that determines the optimal emergency management. ASS1 deficiency (citrullinemia) accumulates citrulline; arginine supplementation is critical. ASL deficiency accumulates argininosuccinic acid; arginine provides both a nitrogen sink and a metabolic substrate. OTC and CPS1 have elevated glutamine rather than citrulline. Nitrogen scavenger selection, dialysis thresholds, and nutritional management all vary by UCD subtype. Molecular diagnosis before the first hyperammonemic crisis enables creation of a gene-specific emergency protocol that reduces brain damage during subsequent episodes.

mRNA therapy for OTC deficiency in clinical trials: molecular confirmation required, and early enrollment maximizes benefit before cumulative brain injury

mRNA therapy delivering functional OTC mRNA via lipid nanoparticles to hepatocytes is in advanced clinical development. This approach could provide OTC enzyme activity without liver transplantation, avoiding the surgical risk, lifelong immunosuppression, and limited organ availability of transplantation. Trial enrollment requires confirmed OTC molecular diagnosis. Early enrollment, before repeated hyperammonemic crises have caused cumulative neurological injury, maximizes the potential cognitive benefit of restoring OTC activity.

Další metabolic conditions

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Jeden test. Odpovědi na celý život.

Jedna souprava, zaslaná domů. Celý váš genom je sekvenován na klinickém standardu používaném pro diagnostická rozhodnutí. Zprávy připravené pro lékaře doručíme do vašeho Genome Manageru během 6–8 týdnů — trvale platné a průběžně aktualizované s vývojem vědy.

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