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Saccharopinuria

MedGen UID:
75693
Concept ID:
C0268556
Disease or Syndrome
Synonyms: HYPERLYSINEMIA, TYPE II; Saccharopine dehydrogenase deficiency
SNOMED CT: Saccharopine dehydrogenase deficiency (58558003); Saccharopinuria (111397004)
 
HPO: HP:0034028
Monarch Initiative: MONDO:0010005
OMIM®: 268700
Orphanet: ORPHA3124

Definition

Saccharopinuria, also known as hyperlysinemia type II, is an autosomal recessive metabolic condition with few, if any, clinical manifestations. Hyperlysinemia type II and hyperlysinemia type I (238700) both result from deficiency of the bifunctional enzyme AASS (605113) on chromosome 7q31. The AASS gene encodes lysine alpha-ketoglutarate reductase and saccharopine dehydrogenase, which catalyze, respectively, the sequential conversion of lysine to saccharopine and saccharopine to alpha-aminoadipic semialdehyde and glutamate (summary by Tondo et al., 2013). In hyperlysinemia type I, both enzymatic functions of AASS are defective and patients have increased serum lysine and possibly increased saccharopine; in hyperlysinemia type II, most of the first enzymatic function is retained, and patients tend to have isolated saccharopine increase (Cox, 1985; Cox et al., 1986). [from OMIM]

Additional description

From MedlinePlus Genetics
Hyperlysinemia is an inherited condition characterized by elevated blood levels of the amino acid lysine, a building block of most proteins. Hyperlysinemia is caused by the shortage (deficiency) of the enzyme that breaks down lysine. Hyperlysinemia typically causes no health problems, and most people with elevated lysine levels are unaware that they have this condition. Rarely, people with hyperlysinemia have intellectual disability or behavioral problems. It is not clear whether these problems are due to hyperlysinemia or another cause.  https://medlineplus.gov/genetics/condition/hyperlysinemia

Clinical features

From HPO
Saccharopinuria
MedGen UID:
75693
Concept ID:
C0268556
Disease or Syndrome
Saccharopinuria, also known as hyperlysinemia type II, is an autosomal recessive metabolic condition with few, if any, clinical manifestations. Hyperlysinemia type II and hyperlysinemia type I (238700) both result from deficiency of the bifunctional enzyme AASS (605113) on chromosome 7q31. The AASS gene encodes lysine alpha-ketoglutarate reductase and saccharopine dehydrogenase, which catalyze, respectively, the sequential conversion of lysine to saccharopine and saccharopine to alpha-aminoadipic semialdehyde and glutamate (summary by Tondo et al., 2013). In hyperlysinemia type I, both enzymatic functions of AASS are defective and patients have increased serum lysine and possibly increased saccharopine; in hyperlysinemia type II, most of the first enzymatic function is retained, and patients tend to have isolated saccharopine increase (Cox, 1985; Cox et al., 1986).
Hyperlysinuria
MedGen UID:
867368
Concept ID:
C4021733
Finding
An increased concentration of lysine in the urine.
Histidinuria
MedGen UID:
1731918
Concept ID:
C5399766
Finding
An increased concentration of histidine in the urine.
Citrullinuria
MedGen UID:
1830384
Concept ID:
C5779778
Finding
The amount of citrulline in the urine, when normalized for urine concentration, is above the upper limit of normal.
Elevated urinary saccharopine level
MedGen UID:
1053672
Concept ID:
CN377094
Finding
The amount of saccharopine in the urine, when normalized to urine concentration, is above the upper limit of normal.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Spastic diplegia
MedGen UID:
44181
Concept ID:
C0023882
Disease or Syndrome
Spasticity (neuromuscular hypertonia) primarily in the muscles of the legs, hips, and pelvis.
EEG abnormality
MedGen UID:
56235
Concept ID:
C0151611
Finding
Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp.
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.
Elevated circulating saccharopine concentration
MedGen UID:
1841772
Concept ID:
C5826818
Finding
An increased concentration of saccharopine in the blood circulation. L-saccharopine is the N(6)-(1,3-dicarboxypropan-1-yl) derivative of L-lysine.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSaccharopinuria
Follow this link to review classifications for Saccharopinuria in Orphanet.

Conditions with this feature

Saccharopinuria
MedGen UID:
75693
Concept ID:
C0268556
Disease or Syndrome
Saccharopinuria, also known as hyperlysinemia type II, is an autosomal recessive metabolic condition with few, if any, clinical manifestations. Hyperlysinemia type II and hyperlysinemia type I (238700) both result from deficiency of the bifunctional enzyme AASS (605113) on chromosome 7q31. The AASS gene encodes lysine alpha-ketoglutarate reductase and saccharopine dehydrogenase, which catalyze, respectively, the sequential conversion of lysine to saccharopine and saccharopine to alpha-aminoadipic semialdehyde and glutamate (summary by Tondo et al., 2013). In hyperlysinemia type I, both enzymatic functions of AASS are defective and patients have increased serum lysine and possibly increased saccharopine; in hyperlysinemia type II, most of the first enzymatic function is retained, and patients tend to have isolated saccharopine increase (Cox, 1985; Cox et al., 1986).

Recent clinical studies

Etiology

Cederbaum SD, Shaw KN, Dancis J, Hutzler J, Blaskovics JC
J Pediatr 1979 Aug;95(2):234-8. doi: 10.1016/s0022-3476(79)80657-5. PMID: 571908
Dancis J, Hutzler J, Cox RP
Am J Hum Genet 1979 May;31(3):290-9. PMID: 463877Free PMC Article

Diagnosis

Pérez B, Gutiérrez-Solana LG, Verdú A, Merinero B, Yuste-Checa P, Ruiz-Sala P, Calvo R, Jalan A, Marín LL, Campos O, Ruiz MÁ, San Miguel M, Vázquez M, Castro M, Ferrer I, Navarrete R, Desviat LR, Lapunzina P, Ugarte M, Pérez-Cerdá C
Epilepsia 2013 Feb;54(2):239-48. Epub 2013 Jan 25 doi: 10.1111/epi.12083. PMID: 23350806
Cederbaum SD, Shaw KN, Dancis J, Hutzler J, Blaskovics JC
J Pediatr 1979 Aug;95(2):234-8. doi: 10.1016/s0022-3476(79)80657-5. PMID: 571908
Dancis J, Hutzler J, Cox RP
Am J Hum Genet 1979 May;31(3):290-9. PMID: 463877Free PMC Article

Therapy

Pérez B, Gutiérrez-Solana LG, Verdú A, Merinero B, Yuste-Checa P, Ruiz-Sala P, Calvo R, Jalan A, Marín LL, Campos O, Ruiz MÁ, San Miguel M, Vázquez M, Castro M, Ferrer I, Navarrete R, Desviat LR, Lapunzina P, Ugarte M, Pérez-Cerdá C
Epilepsia 2013 Feb;54(2):239-48. Epub 2013 Jan 25 doi: 10.1111/epi.12083. PMID: 23350806

Prognosis

Sacksteder KA, Biery BJ, Morrell JC, Goodman BK, Geisbrecht BV, Cox RP, Gould SJ, Geraghty MT
Am J Hum Genet 2000 Jun;66(6):1736-43. Epub 2000 Apr 20 doi: 10.1086/302919. PMID: 10775527Free PMC Article

Clinical prediction guides

Sacksteder KA, Biery BJ, Morrell JC, Goodman BK, Geisbrecht BV, Cox RP, Gould SJ, Geraghty MT
Am J Hum Genet 2000 Jun;66(6):1736-43. Epub 2000 Apr 20 doi: 10.1086/302919. PMID: 10775527Free PMC Article

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