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Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins(LFIT)

MedGen UID:
480294
Concept ID:
C3278664
Disease or Syndrome
Synonyms: Liver failure acute infantile; LIVER FAILURE, INFANTILE, TRANSIENT
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): TRMU (22q13.31)
 
Monarch Initiative: MONDO:0013111
OMIM®: 613070
Orphanet: ORPHA217371

Definition

Acute infantile liver failure resulting from TRMU mutation is a transient disorder of hepatic function. In addition to elevated liver enzymes, jaundice, vomiting, coagulopathy, and hyperbilirubinemia, the presence of increased serum lactate is consistent with a defect in mitochondrial respiratory function. With supportive care, patients who survive the initial acute episode can recover and show normal development (Zeharia et al., 2009). See also transient infantile mitochondrial myopathy (MMIT; 500009), which is a similar disorder. A more severe, permanent disorder with some overlapping features is associated with mitochondrial DNA depletion (251880). See ILFS1 (615438) for information on syndromic infantile liver failure. [from OMIM]

Clinical features

From HPO
Dicarboxylic aciduria
MedGen UID:
343550
Concept ID:
C1856432
Finding
An increased concentration of dicarboxylic acid in the urine.
3-hydroxydicarboxylic aciduria
MedGen UID:
870283
Concept ID:
C4024725
Finding
The concentration of 2-hydroxydicarboxylic acid in the urine, normalized for urine concentration, is above the upper limit of normal.
Lacticaciduria
MedGen UID:
871116
Concept ID:
C4025585
Finding
An increased concentration of lactic acid in the urine.
Abdominal distention
MedGen UID:
34
Concept ID:
C0000731
Finding
Distention of the abdomen.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Acute liver failure
MedGen UID:
58125
Concept ID:
C0162557
Disease or Syndrome
Hepatic failure refers to the inability of the liver to perform its normal synthetic and metabolic functions, which can result in coagulopathy and alteration in the mental status of a previously healthy individual. Hepatic failure is defined as acute if there is onset of encephalopathy within 8 weeks of the onset of symptoms in a patient with a previously healthy liver.
Macrovesicular hepatic steatosis
MedGen UID:
373290
Concept ID:
C1837256
Finding
A form of hepatic steatosis characterized by the presence of large, lipid-laden vesicles in the affected hepatocytes.
Microvesicular hepatic steatosis
MedGen UID:
376784
Concept ID:
C1850415
Finding
A form of hepatic steatosis characterized by the presence of small, lipid-laden vesicles in the affected hepatocytes.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Irritability
MedGen UID:
397841
Concept ID:
C2700617
Mental Process
A proneness to anger, i.e., a tendency to become easily bothered or annoyed.
Prolonged prothrombin time
MedGen UID:
208879
Concept ID:
C0853225
Finding
Increased time to coagulation in the prothrombin time test, which is a measure of the extrinsic pathway of coagulation. The results of the prothrombin time test are often expressed in terms of the International normalized ratio (INR), which is calculated as a ratio of the patient's prothrombin time (PT) to a control PT standardized for the potency of the thromboplastin reagent developed by the World Health Organization (WHO) using the formula
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Decreased circulating IgG concentration
MedGen UID:
1720114
Concept ID:
C5234937
Finding
An abnormally decreased level of immunoglobulin G (IgG) in blood.
Lactic acidosis
MedGen UID:
1717
Concept ID:
C0001125
Disease or Syndrome
An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.
Elevated circulating alanine aminotransferase concentration
MedGen UID:
57740
Concept ID:
C0151905
Finding
An abnormally high concentration in the circulation of alanine aminotransferase (ALT).
Elevated circulating hepatic transaminase concentration
MedGen UID:
116013
Concept ID:
C0235996
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Hypoalbuminemia
MedGen UID:
68694
Concept ID:
C0239981
Finding
Reduction in the concentration of albumin in the blood.
Hyperbilirubinemia
MedGen UID:
86321
Concept ID:
C0311468
Finding
An increased amount of bilirubin in the blood.
Increased circulating lactate concentration
MedGen UID:
332209
Concept ID:
C1836440
Finding
Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35).
Mitochondrial respiratory chain defects
MedGen UID:
416588
Concept ID:
C2751582
Finding

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAcute infantile liver failure due to synthesis defect of mtDNA-encoded proteins

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