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Purine-nucleoside phosphorylase deficiency

MedGen UID:
75653
Concept ID:
C0268125
Disease or Syndrome
Synonyms: NUCLEOSIDE PHOSPHORYLASE DEFICIENCY; PNP deficiency
SNOMED CT: Purine-nucleoside phosphorylase deficiency (60743005); PNP deficiency (60743005); NP deficiency (60743005); Nucleoside phosphorylase deficiency (60743005); Purine nucleoside phosphorylase deficiency (60743005); PNP - Purine nucleoside phosphorylase deficiency (60743005); Deficiency of purine-nucleoside phosphorylase (60743005); NP - Nucleoside phosphorylase deficiency (60743005); Deficiency of inosine phosphorylase (60743005)
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): PNP (14q11.2)
 
Monarch Initiative: MONDO:0013171
OMIM®: 613179
Orphanet: ORPHA760

Definition

Purine nucleoside phosphorylase deficiency is a rare autosomal recessive immunodeficiency disorder characterized mainly by decreased T-cell function. Some patients also have neurologic impairment (review by Aust et al., 1992). [from OMIM]

Additional description

From MedlinePlus Genetics
Purine nucleoside phosphorylase deficiency is a disorder of the immune system called an immunodeficiency. Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as bacteria and viruses.

People with purine nucleoside phosphorylase deficiency have low numbers of immune system cells called T cells, which normally recognize and attack foreign invaders to prevent infection. Some affected individuals also have low numbers of other immune system cells called B cells, which normally help fight infections by producing immune proteins called antibodies (or immunoglobulins). These proteins target foreign invaders and mark them for destruction. The most severely affected individuals, who lack T cells and B cells, have a serious condition called severe combined immunodeficiency (SCID).

The shortage of immune system cells in people with purine nucleoside phosphorylase deficiency results in repeated and persistent infections typically beginning in infancy or early childhood. Infections most commonly affect the sinuses and lungs. These infections are often caused by "opportunistic" organisms that ordinarily do not cause illness in people with a normal immune system. The infections can be very serious or life-threatening, and without successful treatment to restore immune function, children with purine nucleoside phosphorylase deficiency usually do not survive past childhood.

Infants with purine nucleoside phosphorylase deficiency typically grow more slowly than healthy babies. About two-thirds of individuals with this condition also have neurological problems, which may include developmental delay, intellectual disability, difficulty with balance and coordination (ataxia), and muscle stiffness (spasticity). People with purine nucleoside phosphorylase deficiency are also at increased risk of developing autoimmune disorders, which occur when the immune system malfunctions and attacks the body's tissues and organs.  https://medlineplus.gov/genetics/condition/purine-nucleoside-phosphorylase-deficiency

Clinical features

From HPO
Lymphoma
MedGen UID:
44223
Concept ID:
C0024299
Neoplastic Process
A cancer originating in lymphocytes and presenting as a solid tumor of lymhpoid cells.
Recurrent urinary tract infections
MedGen UID:
120466
Concept ID:
C0262655
Disease or Syndrome
Repeated infections of the urinary tract.
Decreased urinary urate
MedGen UID:
868715
Concept ID:
C4023118
Finding
Decreased concentration of urate in the urine.
Elevated urinary inosine level
MedGen UID:
1052458
Concept ID:
CN376443
Finding
The amount of inosine in the urine, normalized for urine concentration, is above the upper limit of normal.
Elevated urinary guanosine level
MedGen UID:
1053612
Concept ID:
CN376445
Finding
The amount of guanosine in the urine, normalized for urine concentration, is above the upper limit of normal.
Cerebral vasculitis
MedGen UID:
68652
Concept ID:
C0238051
Disease or Syndrome
Inflammation of the blood vessels within the brain.
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.
Atypical behavior
MedGen UID:
14048
Concept ID:
C0004941
Sign or Symptom
Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Spastic diplegia
MedGen UID:
44181
Concept ID:
C0023882
Disease or Syndrome
Spasticity (neuromuscular hypertonia) primarily in the muscles of the legs, hips, and pelvis.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Tetraparesis
MedGen UID:
78731
Concept ID:
C0270790
Finding
Weakness of all four limbs.
Delayed gross motor development
MedGen UID:
332508
Concept ID:
C1837658
Finding
A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Pure red-cell aplasia
MedGen UID:
11154
Concept ID:
C0034902
Disease or Syndrome
A type of anemia resulting from suppression of erythropoiesis with little or no abnormality of leukocyte or platelet production. Erythroblasts are virtually absent in bone marrow; however, leukocyte and platelet production show little or no reduction.
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).
Recurrent upper respiratory tract infections
MedGen UID:
154380
Concept ID:
C0581381
Disease or Syndrome
An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).
Recurrent lower respiratory tract infections
MedGen UID:
756211
Concept ID:
C3163798
Disease or Syndrome
An increased susceptibility to lower respiratory tract infections as manifested by a history of recurrent lower respiratory tract infections.
Autoimmune hemolytic anemia
MedGen UID:
1918
Concept ID:
C0002880
Disease or Syndrome
An autoimmune form of hemolytic anemia.
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Otitis media
MedGen UID:
45253
Concept ID:
C0029882
Disease or Syndrome
Inflammation or infection of the middle ear.
Pneumonia
MedGen UID:
10813
Concept ID:
C0032285
Disease or Syndrome
Inflammation of any part of the lung parenchyma.
Sinusitis
MedGen UID:
20772
Concept ID:
C0037199
Disease or Syndrome
Inflammation of the paranasal sinuses owing to a viral, bacterial, or fungal infection, allergy, or an autoimmune reaction.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Autoimmune thrombocytopenia
MedGen UID:
116621
Concept ID:
C0242584
Disease or Syndrome
The presence of thrombocytopenia in combination with detection of antiplatelet antibodies.
Neutropenia in presence of anti-neutropil antibodies
MedGen UID:
137947
Concept ID:
C0340971
Disease or Syndrome
A type of neutropenia that is observed in the presence of granulocyte-specific antibodies.
Recurrent opportunistic infections
MedGen UID:
330439
Concept ID:
C1832324
Finding
Increased susceptibility to opportunistic infections, as manifested by recurrent episodes of infection by opportunistic agents, i.e., by microorganisms that do not usually cause disease in a healthy host, but are able to infect a host with a compromised immune system.
Recurrent viral infections
MedGen UID:
332357
Concept ID:
C1837066
Finding
Increased susceptibility to viral infections, as manifested by recurrent episodes of viral infection.
Recurrent bacterial infections
MedGen UID:
334943
Concept ID:
C1844383
Finding
Increased susceptibility to bacterial infections, as manifested by recurrent episodes of bacterial infection.
Abnormality of B cell physiology
MedGen UID:
341411
Concept ID:
C1849242
Finding
An abnormality of the physiological functioning of B cells.
Impaired T cell function
MedGen UID:
395415
Concept ID:
C1860127
Cell or Molecular Dysfunction
Abnormally reduced ability of T cells to perform their functions in cell-mediated immunity.
Lymph node hypoplasia
MedGen UID:
892318
Concept ID:
C4025683
Finding
Underdevelopment of the lymph nodes.
Decreased lymphocyte proliferation in response to mitogen
MedGen UID:
1615224
Concept ID:
C4531166
Cell or Molecular Dysfunction
A decreased proliferative response of lymphocytes in vitro or in vivo, when stimulated with mitogens, such as phytohemagglutinin (PHA).
Hypouricemia
MedGen UID:
113163
Concept ID:
C0221333
Finding
An abnormally low level of uric acid in the blood.
Increased circulating inosine concentration
MedGen UID:
1784908
Concept ID:
C5539526
Finding
An increased concentration of inosine in the blood circulation.
Increased circulating guanosine concentration
MedGen UID:
1783036
Concept ID:
C5539527
Finding
Increased concentration of guanosine in the blood circulation.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVPurine-nucleoside phosphorylase deficiency
Follow this link to review classifications for Purine-nucleoside phosphorylase deficiency in Orphanet.

Professional guidelines

PubMed

Ricci S, Guarnieri V, Capitanini F, Pelosi C, Astorino V, Boscia S, Calistri E, Canessa C, Cortimiglia M, Lippi F, Lodi L, Malvagia S, Moriondo M, La Marca G, Azzari C
J Allergy Clin Immunol Pract 2024 Jun;12(6):1622-1630.e4. Epub 2024 Apr 16 doi: 10.1016/j.jaip.2024.04.011. PMID: 38636590
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Simmonds HA, Sahota A, Potter CF, Cameron JS
Clin Sci Mol Med 1978 May;54(5):579-84. doi: 10.1042/cs0540579. PMID: 108044

Recent clinical studies

Etiology

Bardou MLD, Henriques MT, Grumach AS
J Pediatr (Rio J) 2021 Mar-Apr;97 Suppl 1(Suppl 1):S75-S83. Epub 2020 Dec 19 doi: 10.1016/j.jped.2020.10.015. PMID: 33347837Free PMC Article
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Zegers BJ, Stoop JW
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Diagnosis

Torun B, Bilgin A, Orhan D, Gocmen R, Kılıc SS, Kuskonmaz B, Cetinkaya D, Tezcan I, Cagdas D
Eur J Med Genet 2022 Mar;65(3):104428. Epub 2022 Jan 19 doi: 10.1016/j.ejmg.2022.104428. PMID: 35063692
Hu Q, Qin Y, Ji S, Shi X, Dai W, Fan G, Li S, Xu W, Liu W, Liu M, Zhang Z, Ye Z, Zhou Z, Yang J, Zhuo Q, Yu X, Li M, Xu X
Cancer Res 2021 Oct 1;81(19):4964-4980. Epub 2021 Aug 12 doi: 10.1158/0008-5472.CAN-20-0414. PMID: 34385182
Bardou MLD, Henriques MT, Grumach AS
J Pediatr (Rio J) 2021 Mar-Apr;97 Suppl 1(Suppl 1):S75-S83. Epub 2020 Dec 19 doi: 10.1016/j.jped.2020.10.015. PMID: 33347837Free PMC Article
Fedoriw A, Rajapurkar SR, O'Brien S, Gerhart SV, Mitchell LH, Adams ND, Rioux N, Lingaraj T, Ribich SA, Pappalardi MB, Shah N, Laraio J, Liu Y, Butticello M, Carpenter CL, Creasy C, Korenchuk S, McCabe MT, McHugh CF, Nagarajan R, Wagner C, Zappacosta F, Annan R, Concha NO, Thomas RA, Hart TK, Smith JJ, Copeland RA, Moyer MP, Campbell J, Stickland K, Mills J, Jacques-O'Hagan S, Allain C, Johnston D, Raimondi A, Porter Scott M, Waters N, Swinger K, Boriack-Sjodin A, Riera T, Shapiro G, Chesworth R, Prinjha RK, Kruger RG, Barbash O, Mohammad HP
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Cell Rep 2016 Apr 19;15(3):574-587. Epub 2016 Apr 7 doi: 10.1016/j.celrep.2016.03.043. PMID: 27068473

Therapy

Karaaslan BG, Turan I, Aydemir S, Meric ZA, Atay D, Akcay A, Sari AA, Hershfield M, Cipe F, Aksoy BA, Ersoy GZ, Bozkurt C, Demirkol YK, Ozturk G, Aydogmus C, Kiykim A, Cokugras H
J Clin Immunol 2023 Nov;43(8):2062-2075. Epub 2023 Sep 20 doi: 10.1007/s10875-023-01585-6. PMID: 37726596
Smith CR, Aranda R, Bobinski TP, Briere DM, Burns AC, Christensen JG, Clarine J, Engstrom LD, Gunn RJ, Ivetac A, Jean-Baptiste R, Ketcham JM, Kobayashi M, Kuehler J, Kulyk S, Lawson JD, Moya K, Olson P, Rahbaek L, Thomas NC, Wang X, Waters LM, Marx MA
J Med Chem 2022 Feb 10;65(3):1749-1766. Epub 2022 Jan 18 doi: 10.1021/acs.jmedchem.1c01900. PMID: 35041419
Bardou MLD, Henriques MT, Grumach AS
J Pediatr (Rio J) 2021 Mar-Apr;97 Suppl 1(Suppl 1):S75-S83. Epub 2020 Dec 19 doi: 10.1016/j.jped.2020.10.015. PMID: 33347837Free PMC Article
Grunebaum E, Cohen A, Roifman CM
Curr Opin Allergy Clin Immunol 2013 Dec;13(6):630-8. doi: 10.1097/ACI.0000000000000006. PMID: 24113229
Zegers BJ, Stoop JW
Clin Biochem 1983 Feb;16(1):43-7. doi: 10.1016/s0009-9120(83)94381-3. PMID: 6407780

Prognosis

Alizadeh Z, Badalzadeh M, Heydarlou H, Shakerian L, Mahlooji Rad M, Zandieh F, Fazlollahi MR
Arch Iran Med 2023 Dec 1;26(12):712-716. doi: 10.34172/aim.2023.105. PMID: 38431953Free PMC Article
Torun B, Bilgin A, Orhan D, Gocmen R, Kılıc SS, Kuskonmaz B, Cetinkaya D, Tezcan I, Cagdas D
Eur J Med Genet 2022 Mar;65(3):104428. Epub 2022 Jan 19 doi: 10.1016/j.ejmg.2022.104428. PMID: 35063692
Hu Q, Qin Y, Ji S, Shi X, Dai W, Fan G, Li S, Xu W, Liu W, Liu M, Zhang Z, Ye Z, Zhou Z, Yang J, Zhuo Q, Yu X, Li M, Xu X
Cancer Res 2021 Oct 1;81(19):4964-4980. Epub 2021 Aug 12 doi: 10.1158/0008-5472.CAN-20-0414. PMID: 34385182
Fekrvand S, Yazdani R, Abolhassani H, Ghaffari J, Aghamohammadi A
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Markert ML
Immunodefic Rev 1991;3(1):45-81. PMID: 1931007

Clinical prediction guides

Tsui M, Biro J, Chan J, Min W, Dobbs K, Notarangelo LD, Grunebaum E
Sci Rep 2022 May 31;12(1):9084. doi: 10.1038/s41598-022-10935-0. PMID: 35641516Free PMC Article
Bardou MLD, Henriques MT, Grumach AS
J Pediatr (Rio J) 2021 Mar-Apr;97 Suppl 1(Suppl 1):S75-S83. Epub 2020 Dec 19 doi: 10.1016/j.jped.2020.10.015. PMID: 33347837Free PMC Article
He HL, Lee YE, Shiue YL, Lee SW, Chen TJ, Li CF
Medicine (Baltimore) 2015 Dec;94(49):e2271. doi: 10.1097/MD.0000000000002271. PMID: 26656376Free PMC Article
Grunebaum E, Cohen A, Roifman CM
Curr Opin Allergy Clin Immunol 2013 Dec;13(6):630-8. doi: 10.1097/ACI.0000000000000006. PMID: 24113229
Liao P, Toro A, Min W, Lee S, Roifman CM, Grunebaum E
J Gene Med 2008 Dec;10(12):1282-93. doi: 10.1002/jgm.1261. PMID: 18924118

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