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Vacuolated lymphocytes

MedGen UID:
332307
Concept ID:
C1836855
Finding
Synonym: Enlarged lysosomal vacuoles in lymphocytes
 
HPO: HP:0001922

Definition

The presence of clear, sharply defined vacuoles in the lymphocyte cytoplasm. [from HPO]

Conditions with this feature

Fucosidosis
MedGen UID:
5288
Concept ID:
C0016788
Disease or Syndrome
Fucosidosis is an autosomal recessive lysosomal storage disease caused by defective alpha-L-fucosidase with accumulation of fucose in the tissues. Clinical features include angiokeratoma, progressive psychomotor retardation, neurologic signs, coarse facial features, and dysostosis multiplex. Fucosidosis has been classified into 2 major types. Type 1 is characterized by rapid psychomotor regression and severe neurologic deterioration beginning at about 6 months of age, elevated sweat sodium chloride, and death within the first decade of life. Type 2 is characterized by milder psychomotor retardation and neurologic signs, the development of angiokeratoma corporis diffusum, normal sweat salinity, and longer survival (Kousseff et al., 1976).
Deficiency of alpha-mannosidase
MedGen UID:
7467
Concept ID:
C0024748
Disease or Syndrome
Alpha-mannosidosis encompasses a continuum of clinical findings from mild to severe. Three major clinical subtypes have been suggested: A mild form recognized after age ten years with absence of skeletal abnormalities, myopathy, and slow progression (type 1). A moderate form recognized before age ten years with presence of skeletal abnormalities, myopathy, and slow progression (type 2). A severe form manifested as prenatal loss or early death from progressive central nervous system involvement or infection (type 3). Individuals with a milder phenotype have mild-to-moderate intellectual disability, impaired hearing, characteristic coarse features, clinical or radiographic skeletal abnormalities, immunodeficiency, and primary central nervous system disease – mainly cerebellar involvement causing ataxia. Periods of psychiatric symptoms are common. Associated medical problems can include corneal opacities, hepatosplenomegaly, aseptic destructive arthritis, and metabolic myopathy. Alpha-mannosidosis is insidiously progressive; some individuals may live into the sixth decade.
Aspartylglucosaminuria
MedGen UID:
78649
Concept ID:
C0268225
Disease or Syndrome
Aspartylglucosaminuria (AGU) is a severe autosomal recessive lysosomal storage disorder that involves the central nervous system and causes skeletal abnormalities as well as connective tissue lesions. The most characteristic feature is progressive mental retardation. The disorder is caused by deficient activity of the lysosomal enzyme glycosylasparaginase, which results in body fluid and tissue accumulation of a series of glycoasparagines, i.e., glycoconjugates with an aspartylglucosamine moiety at the reducing end. AGU belongs to the group of disorders commonly referred to as the Finnish disease heritage (summary by Mononen et al., 1993 and Arvio and Arvio, 2002).
Infantile GM1 gangliosidosis
MedGen UID:
75665
Concept ID:
C0268271
Disease or Syndrome
GLB1-related disorders comprise two phenotypically distinct lysosomal storage disorders: GM1 gangliosidosis and mucopolysaccharidosis type IVB (MPS IVB). The phenotype of GM1 gangliosidosis constitutes a spectrum ranging from severe (infantile) to intermediate (late-infantile and juvenile) to mild (chronic/adult). Type I (infantile) GM1 gangliosidosis begins before age 12 months. Prenatal manifestations may include nonimmune hydrops fetalis, intrauterine growth restriction, and placental vacuolization; congenital dermal melanocytosis (Mongolian spots) may be observed. Macular cherry-red spot is detected on eye exam. Progressive central nervous system dysfunction leads to spasticity and rapid regression; blindness, deafness, decerebrate rigidity, seizures, feeding difficulties, and oral secretions are observed. Life expectancy is two to three years. Type II can be subdivided into the late-infantile (onset age 1-3 years) and juvenile (onset age 3-10 years) phenotypes. Central nervous system dysfunction manifests as progressive cognitive, motor, and speech decline as measured by psychometric testing. There may be mild corneal clouding, hepatosplenomegaly, and/or cardiomyopathy; the typical course is characterized by progressive neurologic decline, progressive skeletal disease in some individuals (including kyphosis and avascular necrosis of the femoral heads), and progressive feeding difficulties leading to aspiration risk. Type III begins in late childhood to the third decade with generalized dystonia leading to unsteady gait and speech disturbance followed by extrapyramidal signs including akinetic-rigid parkinsonism. Cardiomyopathy develops in some and skeletal involvement occurs in most. Intellectual impairment is common late in the disease with prognosis directly related to the degree of neurologic impairment. MPS IVB is characterized by skeletal dysplasia with specific findings of axial and appendicular dysostosis multiplex, short stature (below 15th centile in adults), kyphoscoliosis, coxa/genu valga, joint laxity, platyspondyly, and odontoid hypoplasia. First signs and symptoms may be apparent at birth. Bony involvement is progressive, with more than 84% of adults requiring ambulation aids; life span does not appear to be limited. Corneal clouding is detected in some individuals and cardiac valvular disease may develop.
Neuronal ceroid lipofuscinosis 3
MedGen UID:
155549
Concept ID:
C0751383
Disease or Syndrome
The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The clinical course includes progressive dementia, seizures, and progressive visual failure (Mole et al., 2005). The hallmark of CLN3 is the ultrastructural pattern of lipopigment with a 'fingerprint' profile, which can have 3 different appearances: pure within a lysosomal residual body; in conjunction with curvilinear or rectilinear profiles; and as a small component within large membrane-bound lysosomal vacuoles. The combination of fingerprint profiles within lysosomal vacuoles is a regular feature of blood lymphocytes from patients with CLN3 (Mole et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (256730).
Sialic acid storage disease, severe infantile type
MedGen UID:
203367
Concept ID:
C1096902
Disease or Syndrome
Free sialic acid storage disorders (FSASDs) are a spectrum of neurodegenerative disorders resulting from increased lysosomal storage of free sialic acid. Historically, FSASD was divided into separate allelic disorders: Salla disease, intermediate severe Salla disease, and infantile free sialic acid storage disease (ISSD). The mildest type was Salla disease, characterized by normal appearance and absence of neurologic findings at birth, followed by slowly progressive neurologic deterioration resulting in mild-to-moderate psychomotor delays, spasticity, athetosis, and epileptic seizures. Salla disease was named for a municipality in Finnish Lapland where a specific founder variant is relatively prevalent. However, the term Salla has been used in the literature to refer to less severe FSASD. More severe FSASD is historically referred to as ISSD, and is characterized by severe developmental delay, coarse facial features, hepatosplenomegaly, and cardiomegaly; death usually occurs in early childhood.
Salla disease
MedGen UID:
203368
Concept ID:
C1096903
Disease or Syndrome
Free sialic acid storage disorders (FSASDs) are a spectrum of neurodegenerative disorders resulting from increased lysosomal storage of free sialic acid. Historically, FSASD was divided into separate allelic disorders: Salla disease, intermediate severe Salla disease, and infantile free sialic acid storage disease (ISSD). The mildest type was Salla disease, characterized by normal appearance and absence of neurologic findings at birth, followed by slowly progressive neurologic deterioration resulting in mild-to-moderate psychomotor delays, spasticity, athetosis, and epileptic seizures. Salla disease was named for a municipality in Finnish Lapland where a specific founder variant is relatively prevalent. However, the term Salla has been used in the literature to refer to less severe FSASD. More severe FSASD is historically referred to as ISSD, and is characterized by severe developmental delay, coarse facial features, hepatosplenomegaly, and cardiomegaly; death usually occurs in early childhood.
Neuronal ceroid lipofuscinosis 9
MedGen UID:
332304
Concept ID:
C1836841
Disease or Syndrome
The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The clinical course includes progressive dementia, seizures, and progressive visual failure (Mole et al., 2005). For a discussion of genetic heterogeneity of neuronal ceroid lipofuscinosis, see CLN1 (256730).
Neuronal ceroid lipofuscinosis 5
MedGen UID:
376792
Concept ID:
C1850442
Disease or Syndrome
The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The lipopigment patterns observed most often in CLN5 comprise mixed combinations of 'granular,' 'curvilinear,' and 'fingerprint' profiles. The clinical course includes progressive dementia, seizures, and progressive visual failure (Mole et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (256730).
Neuronal ceroid lipofuscinosis 1
MedGen UID:
340540
Concept ID:
C1850451
Disease or Syndrome
The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The lipopigment pattern seen most often in CLN1 is referred to as granular osmiophilic deposits (GROD). The patterns most often observed in CLN2 and CLN3 are 'curvilinear' and 'fingerprint' profiles, respectively. CLN4, CLN5, CLN6, CLN7, and CLN8 show mixed combinations of granular, curvilinear, fingerprint, and rectilinear profiles. The clinical course includes progressive dementia, seizures, and progressive visual failure (Mole et al., 2005). Zeman and Dyken (1969) referred to these conditions as the 'neuronal ceroid lipofuscinoses.' Goebel (1995) provided a comprehensive review of the NCLs and noted that they are possibly the most common group of neurodegenerative diseases in children. Mole et al. (2005) provided a detailed clinical and genetic review of the neuronal ceroid lipofuscinoses. Genetic Heterogeneity of Neuronal Ceroid Lipofuscinosis See also CLN2 (204500), caused by mutation in the TPP1 gene (607998) on chromosome 11p15; CLN3 (204200), caused by mutation in the CLN3 gene (607042) on 16p12; CLN4 (162350), caused by mutation in the DNAJC5 gene (611203) on 20q13; CLN5 (256731), caused by mutation in the CLN5 gene (608102) on 13q22; CLN6A (601780) and CLN6B (204300), both caused by mutation in the CLN6 gene (606725) on 15q21; CLN7 (610951), caused by mutation in the MFSD8 gene (611124) on 4q28; CLN8 (600143) and the Northern epilepsy variant of CLN8 (610003), both caused by mutation in the CLN8 gene (607837) on 8p23; CLN10 (610127), caused by mutation in the CTSD gene (116840) on 11p15; CLN11 (614706), caused by mutation in the GRN gene (138945) on 17q21; CLN13 (615362), caused by mutation in the CTSF gene (603539) on 11q13; and CLN14 (611726), caused by mutation in the KCTD7 gene (611725) on 7q11. CLN9 (609055) has not been molecularly characterized. A disorder that was formerly designated neuronal ceroid lipofuscinosis-12 (CLN12) is now considered to be a variable form of Kufor-Rakeb syndrome (KRS; 606693).
Sialidosis type 2
MedGen UID:
924303
Concept ID:
C4282398
Disease or Syndrome
Sialidosis is an autosomal recessive disorder characterized by the progressive lysosomal storage of sialylated glycopeptides and oligosaccharides caused by a deficiency of the enzyme neuraminidase. Common to the sialidoses is the accumulation and/or excretion of sialic acid (N-acetylneuraminic acid) covalently linked ('bound') to a variety of oligosaccharides and/or glycoproteins (summary by Lowden and O'Brien, 1979). The sialidoses are distinct from the sialurias in which there is storage and excretion of 'free' sialic acid, rather than 'bound' sialic acid; neuraminidase activity in sialuria is normal or elevated. Salla disease (604369) is a form of 'free' sialic acid disease. Classification Lowden and O'Brien (1979) provided a logical nosology of neuraminidase deficiency into sialidosis type I and type II. Type I is the milder form, also known as the 'normosomatic' type or the cherry red spot-myoclonus syndrome. Sialidosis type II is the more severe form with an earlier onset, and is also known as the 'dysmorphic' type. Type II has been subdivided into juvenile and infantile forms. Other terms for sialidosis type II are mucolipidosis I and lipomucopolysaccharidosis.

Professional guidelines

PubMed

Taconet S, Dreux S, Guimiot F, Pettazzoni M, Allaf B, Spaggiari E, Rosenblatt J, Khung-Savatovsky S
Prenat Diagn 2020 Apr;40(5):605-611. Epub 2020 Feb 11 doi: 10.1002/pd.5657. PMID: 32003481

Recent clinical studies

Etiology

Taconet S, Dreux S, Guimiot F, Pettazzoni M, Allaf B, Spaggiari E, Rosenblatt J, Khung-Savatovsky S
Prenat Diagn 2020 Apr;40(5):605-611. Epub 2020 Feb 11 doi: 10.1002/pd.5657. PMID: 32003481
Wright GA, Georgiou M, Robson AG, Ali N, Kalhoro A, Holthaus SK, Pontikos N, Oluonye N, de Carvalho ER, Neveu MM, Weleber RG, Michaelides M
Ophthalmol Retina 2020 Apr;4(4):433-445. Epub 2019 Nov 13 doi: 10.1016/j.oret.2019.11.005. PMID: 31926949Free PMC Article
Chang X, Huang Y, Meng H, Jiang Y, Wu Y, Xiong H, Wang S, Qin J
Brain Dev 2012 Oct;34(9):739-45. Epub 2012 Jan 14 doi: 10.1016/j.braindev.2011.12.005. PMID: 22245569
Vargas-Díez E, Chabás A, Coll MJ, Sánchez-Pérez J, García-Díez A, Fernández-Herrera JM
Br J Dermatol 2002 Oct;147(4):760-4. doi: 10.1046/j.1365-2133.2002.04827.x. PMID: 12366426
Kimura S, Goebel HH
Pediatr Neurol 1988 May-Jun;4(3):148-52. doi: 10.1016/0887-8994(88)90002-1. PMID: 3242517

Diagnosis

Sassi M, Khefacha L, Merzigui R, Rakez R, Boukhriss S, Laatiri MA
Br J Haematol 2021 Dec;195(5):649. Epub 2021 Jul 27 doi: 10.1111/bjh.17660. PMID: 34312842Free PMC Article
Taconet S, Dreux S, Guimiot F, Pettazzoni M, Allaf B, Spaggiari E, Rosenblatt J, Khung-Savatovsky S
Prenat Diagn 2020 Apr;40(5):605-611. Epub 2020 Feb 11 doi: 10.1002/pd.5657. PMID: 32003481
Pascarella A, Terracciano C, Farina O, Lombardi L, Esposito T, Napolitano F, Franzese G, Panella G, Tuccillo F, la Marca G, Bernardini S, Boffo S, Giordano A, Di Iorio G, Melone MAB, Sampaolo S
J Cell Physiol 2018 Aug;233(8):5829-5837. Epub 2018 Feb 22 doi: 10.1002/jcp.26365. PMID: 29215735
Santavuori P, Vanhanen SL, Autti T
Eur J Paediatr Neurol 2001;5 Suppl A:157-61. doi: 10.1053/ejpn.2000.0454. PMID: 11588989
Ovali F, Samanci N, Güray A, Akdoğan Z, Akdeniz C, Dağoğlu T, Petorak I
Turk J Pediatr 1998 Jul-Sep;40(3):447-51. PMID: 9763912

Therapy

Sassi M, Khefacha L, Merzigui R, Rakez R, Boukhriss S, Laatiri MA
Br J Haematol 2021 Dec;195(5):649. Epub 2021 Jul 27 doi: 10.1111/bjh.17660. PMID: 34312842Free PMC Article
Wright GA, Georgiou M, Robson AG, Ali N, Kalhoro A, Holthaus SK, Pontikos N, Oluonye N, de Carvalho ER, Neveu MM, Weleber RG, Michaelides M
Ophthalmol Retina 2020 Apr;4(4):433-445. Epub 2019 Nov 13 doi: 10.1016/j.oret.2019.11.005. PMID: 31926949Free PMC Article
Hagemans ML, Stigter RL, van Capelle CI, van der Beek NA, Winkel LP, van Vliet L, Hop WC, Reuser AJ, Beishuizen A, van der Ploeg AT
J Inherit Metab Dis 2010 Apr;33(2):133-9. Epub 2010 Jan 27 doi: 10.1007/s10545-009-9027-4. PMID: 20107902Free PMC Article

Prognosis

Bounds RL, Kuebler J, Cholette JM, Alfieris GM, Emani SM, Wittlieb-Weber CA
World J Pediatr Congenit Heart Surg 2018 Mar;9(2):246-250. Epub 2016 Sep 12 doi: 10.1177/2150135116664701. PMID: 27619328
Chang X, Huang Y, Meng H, Jiang Y, Wu Y, Xiong H, Wang S, Qin J
Brain Dev 2012 Oct;34(9):739-45. Epub 2012 Jan 14 doi: 10.1016/j.braindev.2011.12.005. PMID: 22245569
Vargas-Díez E, Chabás A, Coll MJ, Sánchez-Pérez J, García-Díez A, Fernández-Herrera JM
Br J Dermatol 2002 Oct;147(4):760-4. doi: 10.1046/j.1365-2133.2002.04827.x. PMID: 12366426
Ovali F, Samanci N, Güray A, Akdoğan Z, Akdeniz C, Dağoğlu T, Petorak I
Turk J Pediatr 1998 Jul-Sep;40(3):447-51. PMID: 9763912
Kimura S, Goebel HH
Pediatr Neurol 1988 May-Jun;4(3):148-52. doi: 10.1016/0887-8994(88)90002-1. PMID: 3242517

Clinical prediction guides

Taconet S, Dreux S, Guimiot F, Pettazzoni M, Allaf B, Spaggiari E, Rosenblatt J, Khung-Savatovsky S
Prenat Diagn 2020 Apr;40(5):605-611. Epub 2020 Feb 11 doi: 10.1002/pd.5657. PMID: 32003481
Wright GA, Georgiou M, Robson AG, Ali N, Kalhoro A, Holthaus SK, Pontikos N, Oluonye N, de Carvalho ER, Neveu MM, Weleber RG, Michaelides M
Ophthalmol Retina 2020 Apr;4(4):433-445. Epub 2019 Nov 13 doi: 10.1016/j.oret.2019.11.005. PMID: 31926949Free PMC Article
Hagemans ML, Stigter RL, van Capelle CI, van der Beek NA, Winkel LP, van Vliet L, Hop WC, Reuser AJ, Beishuizen A, van der Ploeg AT
J Inherit Metab Dis 2010 Apr;33(2):133-9. Epub 2010 Jan 27 doi: 10.1007/s10545-009-9027-4. PMID: 20107902Free PMC Article
Hirose Y, Shimizu S, Yoshioka R, Tachibana J, Sugai S, Takiguchi T, Konda S
Jpn J Cancer Res 1990 Apr;81(4):376-82. doi: 10.1111/j.1349-7006.1990.tb02578.x. PMID: 2114391Free PMC Article
Kimura S, Goebel HH
Pediatr Neurol 1988 May-Jun;4(3):148-52. doi: 10.1016/0887-8994(88)90002-1. PMID: 3242517

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