U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Triosephosphate isomerase deficiency(TPID)

MedGen UID:
349893
Concept ID:
C1860808
Disease or Syndrome
Synonyms: TPID; Triose phosphate-isomerase deficiency
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): TPI1 (12p13.31)
 
Monarch Initiative: MONDO:0014221
OMIM®: 615512
Orphanet: ORPHA868

Definition

Triosephosphate isomerase deficiency (TPID) is an autosomal recessive multisystem disorder characterized by congenital hemolytic anemia, and progressive neuromuscular dysfunction beginning in early childhood. Many patients die from respiratory failure in childhood. The neurologic syndrome is variable, but usually includes lower motor neuron dysfunction with hypotonia, muscle weakness and atrophy, and hyporeflexia. Some patients may show additional signs such as dystonic posturing and/or spasticity. Laboratory studies show intracellular accumulation of dihydroxyacetone phosphate (DHAP), particularly in red blood cells (summary by Fermo et al., 2010). [from OMIM]

Additional description

From MedlinePlus Genetics
Triosephosphate isomerase deficiency is a disorder characterized by a shortage of red blood cells (anemia), movement problems, increased susceptibility to infection, and muscle weakness that can affect breathing and heart function.

The anemia in this condition begins in infancy. Since the anemia results from the premature breakdown of red blood cells (hemolysis), it is known as hemolytic anemia. A shortage of red blood cells to carry oxygen throughout the body leads to extreme tiredness (fatigue), pale skin (pallor), and shortness of breath. When the red cells are broken down, iron and a molecule called bilirubin are released; individuals with triosephosphate isomerase deficiency have an excess of these substances circulating in the blood. Excess bilirubin in the blood causes jaundice, which is a yellowing of the skin and the whites of the eyes.

Movement problems typically become apparent by age 2 in people with triosephosphate isomerase deficiency. The movement problems are caused by impairment of motor neurons, which are specialized nerve cells in the brain and spinal cord that control muscle movement. This impairment leads to muscle weakness and wasting (atrophy) and causes the movement problems typical of triosephosphate isomerase deficiency, including involuntary muscle tensing (dystonia), tremors, and weak muscle tone (hypotonia). Affected individuals may also develop seizures.

Weakness of other muscles, such as the heart (a condition known as cardiomyopathy) and the muscle that separates the abdomen from the chest cavity (the diaphragm) can also occur in triosephosphate isomerase deficiency. Diaphragm weakness can cause breathing problems and ultimately leads to respiratory failure.

Individuals with triosephosphate isomerase deficiency are at increased risk of developing infections because they have poorly functioning white blood cells. These immune system cells normally recognize and attack foreign invaders, such as viruses and bacteria, to prevent infection. The most common infections in people with triosephosphate isomerase deficiency are bacterial infections of the respiratory tract.

People with triosephosphate isomerase deficiency often do not survive past childhood due to respiratory failure. In a few rare cases, affected individuals without severe nerve damage or muscle weakness have lived into adulthood.  https://medlineplus.gov/genetics/condition/triosephosphate-isomerase-deficiency

Clinical features

From HPO
Congestive heart failure
MedGen UID:
9169
Concept ID:
C0018802
Disease or Syndrome
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Cholecystitis
MedGen UID:
920
Concept ID:
C0008325
Disease or Syndrome
The presence of inflammatory changes in the gallbladder.
Cholelithiasis
MedGen UID:
3039
Concept ID:
C0008350
Disease or Syndrome
Hard, pebble-like deposits that form within the gallbladder.
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.
Prolonged neonatal jaundice
MedGen UID:
347108
Concept ID:
C1859236
Finding
Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Peripheral neuropathy
MedGen UID:
18386
Concept ID:
C0031117
Disease or Syndrome
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Unsteady gait
MedGen UID:
68544
Concept ID:
C0231686
Finding
A shaky or wobbly manner of walking.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Hemolytic anemia
MedGen UID:
1916
Concept ID:
C0002878
Disease or Syndrome
A type of anemia caused by premature destruction of red blood cells (hemolysis).
Macrocytic anemia
MedGen UID:
1920
Concept ID:
C0002886
Disease or Syndrome
A type of anemia characterized by increased size of erythrocytes with increased mean corpuscular volume (MCV) and increased mean corpuscular hemoglobin (MCH).
Normocytic anemia
MedGen UID:
39310
Concept ID:
C0085577
Disease or Syndrome
A kind of anemia in which the volume of the red blood cells is normal.
Normochromic anemia
MedGen UID:
66731
Concept ID:
C0235983
Finding
Chronic hemolytic anemia
MedGen UID:
237230
Concept ID:
C1387532
Disease or Syndrome
An chronic form of hemolytic anemia.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
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.
Myopathy
MedGen UID:
10135
Concept ID:
C0026848
Disease or Syndrome
A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Progressive muscle weakness
MedGen UID:
68704
Concept ID:
C0240421
Finding
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Respiratory distress
MedGen UID:
96907
Concept ID:
C0476273
Sign or Symptom
Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea.
Respiratory failure
MedGen UID:
257837
Concept ID:
C1145670
Disease or Syndrome
A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits.
Respiratory insufficiency due to muscle weakness
MedGen UID:
812797
Concept ID:
C3806467
Finding
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Oligohydramnios
MedGen UID:
86974
Concept ID:
C0079924
Pathologic Function
Diminished amniotic fluid volume in pregnancy.
Optic disc pallor
MedGen UID:
108218
Concept ID:
C0554970
Finding
A pale yellow discoloration of the optic disc (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVTriosephosphate isomerase deficiency

Recent clinical studies

Prognosis

VanDemark AP, Hrizo SL, Eicher SL, Kowalski J, Myers TD, Pfeifer MR, Riley KN, Koeberl DD, Palladino MJ
Dis Model Mech 2022 May 1;15(5) Epub 2022 May 17 doi: 10.1242/dmm.049261. PMID: 35315486Free PMC Article
Oliver C, Timson DJ
Eur J Med Genet 2017 Jun;60(6):289-298. Epub 2017 Mar 21 doi: 10.1016/j.ejmg.2017.03.008. PMID: 28341520
Aissa K, Kamoun F, Sfaihi L, Ghedira ES, Aloulou H, Kamoun T, Pissard S, Hachicha M
Fetal Pediatr Pathol 2014 Aug;33(4):234-8. Epub 2014 May 19 doi: 10.3109/15513815.2014.915365. PMID: 24840153
Oláh J, Orosz F, Puskás LG, Hackler L Jr, Horányi M, Polgár L, Hollán S, Ovádi J
Biochem J 2005 Dec 15;392(Pt 3):675-83. doi: 10.1042/BJ20050993. PMID: 16086671Free PMC Article
Orosz F, Vértessy BG, Hollán S, Horányi M, Ovádi J
J Theor Biol 1996 Oct 7;182(3):437-47. doi: 10.1006/jtbi.1996.0184. PMID: 8944178

Clinical prediction guides

VanDemark AP, Hrizo SL, Eicher SL, Kowalski J, Myers TD, Pfeifer MR, Riley KN, Koeberl DD, Palladino MJ
Dis Model Mech 2022 May 1;15(5) Epub 2022 May 17 doi: 10.1242/dmm.049261. PMID: 35315486Free PMC Article
Segal J, Mülleder M, Krüger A, Adler T, Scholze-Wittler M, Becker L, Calzada-Wack J, Garrett L, Hölter SM, Rathkolb B, Rozman J, Racz I, Fischer R, Busch DH, Neff F, Klingenspor M, Klopstock T, Grüning NM, Michel S, Lukaszewska-McGreal B, Voigt I, Hartmann L, Timmermann B, Lehrach H, Wolf E, Wurst W, Gailus-Durner V, Fuchs H, H de Angelis M, Schrewe H, Yuneva M, Ralser M
J Inherit Metab Dis 2019 Sep;42(5):839-849. Epub 2019 Jun 11 doi: 10.1002/jimd.12105. PMID: 31111503Free PMC Article
Cabrera N, Torres-Larios A, García-Torres I, Enríquez-Flores S, Perez-Montfort R
Biochim Biophys Acta Gen Subj 2018 Jun;1862(6):1401-1409. Epub 2018 Mar 20 doi: 10.1016/j.bbagen.2018.03.019. PMID: 29571745
Roland BP, Amrich CG, Kammerer CJ, Stuchul KA, Larsen SB, Rode S, Aslam AA, Heroux A, Wetzel R, VanDemark AP, Palladino MJ
Biochim Biophys Acta 2015 Jan;1852(1):61-9. Epub 2014 Oct 16 doi: 10.1016/j.bbadis.2014.10.010. PMID: 25463631Free PMC Article
Orosz F, Oláh J, Ovádi J
IUBMB Life 2006 Dec;58(12):703-15. doi: 10.1080/15216540601115960. PMID: 17424909

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...