Oculocerebrorenal syndrome

Oculocerebrorenal syndrome
Classification and external resources
ICD-10	E72.0
ICD-9-CM	270.8
OMIM	309000
DiseasesDB	29146
eMedicine	oph/516
MeSH	D009800
GeneReviews	Lowe Syndrome

Oculocerebrorenal syndrome (also called Lowe syndrome) is a rare X-linked recessive disorder characterized by congenital cataracts, hypotonia and areflexia, intellectual disability, proximal tubular acidosis, aminoaciduria, phosphaturia, and low-molecular-weight proteinuria. Glaucoma is present in about 50% of cases.

Lowe syndrome can be considered a cause of Fanconi syndrome (bicarbonaturia, renal tubular acidosis, aminoaciduria, phosphaturia, tubular proteinuria, and impaired urine-concentrating ability).^[1]

Presentation

Because it is an X-linked recessive condition, the disease develops mostly in men with very rare occurrences in women, while women are carriers of the disease. It has an estimated prevalence of 1 in 500,000 people.^[2] Boys with Lowe syndrome are born with cataracts in both eyes (the hallmark of the disease). Glaucoma is present in about 50% of the patients with Lowe syndrome, though usually not at birth. While not present at birth, many affected boys develop kidney problems at about one year of age. Renal pathology is characterized by an abnormal loss of certain substances into the urine, including bicarbonate, sodium, potassium, amino acids, organic acids, albumin and other small proteins, calcium, phosphate, glucose, and L-carnitine. This problem, known as Fanconi-type renal tubular dysfunction, can also be seen in other diseases and syndromes.

Genetics

Oculocerebrorenal syndrome has an X-linked recessive mode of inheritance

This syndrome is caused by mutations in the OCRL1 gene which encodes a inositol polyphosphate-5-phosphatase.^[3] At least one mechanism by which these mutations cause this syndrome is by loss of its Rab binding domain.^[4] This protein is associated with the primary cilia of the retinal pigment epithelial cells, fibroblasts and kidney tubular cells.^[5] This suggests that this syndrome is due to dysfunction of the cilia in these cells.^[6]

History

It was first described in 1952 by Charles Lowe and colleagues at the Massachusetts General Hospital in Boston.^[7] Because of the three major organ systems involved (eyes, brain, and kidney), it is also known as oculocerebrorenal syndrome.

Eponym

It is named after Charles Upton Lowe (August 24, 1921 – February 9, 2012 ).^[8]

References

↑ Vilasi A, Cutillas PR, Maher AD, et al. (August 2007). "Combined proteomic and metabonomic studies in three genetic forms of the renal Fanconi syndrome". Am. J. Physiol. Renal Physiol. 293 (2): F456–67. doi:10.1152/ajprenal.00095.2007. PMID 17494094.
↑ Loi M. Lowe Syndrome. Orphanet Journal of Rare Diseases 2006,1:16
↑ Kanık A, Kasap-Demir B, Ateşli R, Eliaçık K, Yavaşcan O, Helvacı M (2013) A novel OCRL1 gene mutation in a Turkish child with Lowe syndrome. The Turkish Journal of Pediatrics 55(1):82-85
↑ Hagemann N, Hou X, Goody RS, Itzen A, Erdmann KS (2012) Crystal structure of the Rab binding domain of OCRL1 in complex with Rab8 and functional implications of the OCRL1/Rab8 module for Lowe syndrome. Small GTPases 3(2):107-10. doi: 10.4161/sgtp.19380
↑ Luo N, West CC, Murga-Zamalloa CA, Sun L, Anderson RM, Wells CD, Weinreb RN, Travers JB, Khanna H, Sun Y (2012) OCRL localizes to the primary cilium: a new role for cilia in Lowe syndrome. Hum Mol Genet 21(15):3333-3344 doi: 10.1093/hmg/dds163
↑ Rbaibi Y, Cui S, Mo D, Carattino M, Rohatgi R, Satlin LM, Szalinski CM, Swanhart LM, Fölsch H, Hukriede NA, Weisz OA. OCRL1 modulates cilia length in renal epithelial cells. Traffic 13(9):1295-305. doi: 10.1111/j.1600-0854.2012.01387.x
↑ Lowe CU, Terrey M, MacLachlan EA (1952). "Organic-aciduria, decreased renal ammonia production, hydrophthalmos, and mental retardation; a clinical entity". AMA American Journal of Diseases of Children. 83 (2): 164–84. PMID 14884753.
↑ synd/3512 at Who Named It?

External links

Inborn error of amino acid metabolism (E70–E72, 270)

K→acetyl-CoA

Lysine/straight chain	Glutaric acidemia type 1 type 2 Hyperlysinemia Pipecolic acidemia Saccharopinuria

Leucine	3-hydroxy-3-methylglutaryl-CoA lyase deficiency 3-Methylcrotonyl-CoA carboxylase deficiency 3-Methylglutaconic aciduria 1 Isovaleric acidemia Maple syrup urine disease

Tryptophan	Hypertryptophanemia

G→pyruvate→citrate

Glycine	D-Glyceric acidemia Glutathione synthetase deficiency Sarcosinemia Glycine→Creatine: GAMT deficiency Glycine encephalopathy

G→glutamate→
α-ketoglutarate

Histidine	Carnosinemia Histidinemia Urocanic aciduria

Proline	Hyperprolinemia Prolidase deficiency

Glutamate/glutamine	SSADHD

G→propionyl-CoA→
succinyl-CoA

Valine	Hypervalinemia Isobutyryl-CoA dehydrogenase deficiency Maple syrup urine disease

Isoleucine	2-Methylbutyryl-CoA dehydrogenase deficiency Beta-ketothiolase deficiency Maple syrup urine disease

Methionine	Cystathioninuria Homocystinuria Hypermethioninemia

General BC/OA	Methylmalonic acidemia Methylmalonyl-CoA mutase deficiency Propionic acidemia

G→fumarate

Phenylalanine/tyrosine

Phenylketonuria	6-Pyruvoyltetrahydropterin synthase deficiency Tetrahydrobiopterin deficiency

Tyrosinemia	Alkaptonuria/Ochronosis Type I tyrosinemia Type II tyrosinemia Type III tyrosinemia/Hawkinsinuria

Tyrosine→Melanin	Albinism: Ocular albinism (1) Oculocutaneous albinism (Hermansky–Pudlak syndrome) Waardenburg syndrome

Tyrosine→Norepinephrine	Dopamine beta hydroxylase deficiency reverse: Brunner syndrome

G→oxaloacetate

Urea cycle/Hyperammonemia (arginine aspartate)	Argininemia Argininosuccinic aciduria Carbamoyl phosphate synthetase I deficiency Citrullinemia N-Acetylglutamate synthase deficiency Ornithine transcarbamylase deficiency/translocase deficiency

Transport/
IE of RTT

Other

Sex linkage: X-linked disorders

X-linked recessive

Immune	Chronic granulomatous disease (CYBB) Wiskott–Aldrich syndrome X-linked severe combined immunodeficiency X-linked agammaglobulinemia Hyper-IgM syndrome type 1 IPEX X-linked lymphoproliferative disease Properdin deficiency

Hematologic	Haemophilia A Haemophilia B X-linked sideroblastic anemia

Endocrine	Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy KAL1 Kallmann syndrome X-linked adrenal hypoplasia congenita

Metabolic	Amino acid: Ornithine transcarbamylase deficiency Oculocerebrorenal syndrome Dyslipidemia: Adrenoleukodystrophy Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency Pyruvate dehydrogenase deficiency Danon disease/glycogen storage disease Type IIb Lipid storage disorder: Fabry's disease Mucopolysaccharidosis: Hunter syndrome Purine-pyrimidine metabolism: Lesch–Nyhan syndrome Mineral: Menkes disease/Occipital horn syndrome

Nervous system	X-linked mental retardation: Coffin–Lowry syndrome MASA syndrome Alpha-thalassemia mental retardation syndrome Siderius X-linked mental retardation syndrome Eye disorders: Color blindness (red and green, but not blue) Ocular albinism (1) Norrie disease Choroideremia Other: Charcot–Marie–Tooth disease (CMTX2-3) Pelizaeus–Merzbacher disease SMAX2

Skin and related tissue	Dyskeratosis congenita Hypohidrotic ectodermal dysplasia (EDA) X-linked ichthyosis X-linked endothelial corneal dystrophy

Neuromuscular	Becker's muscular dystrophy/Duchenne Centronuclear myopathy (MTM1) Conradi–Hünermann syndrome Emery–Dreifuss muscular dystrophy 1

Urologic	Alport syndrome Dent's disease X-linked nephrogenic diabetes insipidus

Bone/tooth	AMELX Amelogenesis imperfecta

No primary system	Barth syndrome McLeod syndrome Smith–Fineman–Myers syndrome Simpson–Golabi–Behmel syndrome Mohr–Tranebjærg syndrome Nasodigitoacoustic syndrome

X-linked dominant

X-linked hypophosphatemia Focal dermal hypoplasia Fragile X syndrome Aicardi syndrome Incontinentia pigmenti Rett syndrome CHILD syndrome Lujan–Fryns syndrome Orofaciodigital syndrome 1 Craniofrontonasal dysplasia

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