Oculocerebrorenal syndrome

Frequency

The Lowe syndrome is very rare. For the general population, the prevalence is estimated at 1 500 000. Are affected thereby all ethnicities. Due to the X-linked inheritance are almost exclusively young affected by the disease. There are extremely rare cases of X - autosome translocations described in which ill also girl at Lowe 's syndrome.

Clinical picture

The Lowe syndrome is a systemic disease that affects multiple organ systems. The affected patients have an intellectual disability ( mental retardation), hypotonia, congenital cataract (cataract ) and a selective proximal tubulopathy.

Cataract

Even at birth, all patients on a dense cataract that develops in the womb ( in utero ). Cataract is caused by a change in migration of the embryonic epithelium. Approximately half of the patients also has glaucoma ( glaucoma ), some with Buphthalmus (eye magnification). Glaucoma usually manifests itself in the first year of life.

Proximal tubulopathy

In the selective proximal tubulopathy is a malfunction in the proximal tubule, which is similar to the De - Toni- Fanconi syndrome. It is therefore also called a secondary Fanconi syndrome. The proximal tubulopathy can be varied greatly from patient to patient, but worsens with age and on. At the time of her birth, many children are still without symptoms but occur during the first months of life and is characterized by bicarbonate, salt and water loss. These mineral losses lead the children to a failure to thrive. In the second decade of life, most patients develop chronic renal failure, which can lead to ESRD. The latter requires renal replacement therapy.

The other symptoms correspond to the de Toni- Fanconi syndrome: proteinuria and renal tubular acidosis. The loss of phosphate by the kidney leads to renal rickets, osteomalacia and spontaneous fractures. The increased calcium excretion in the urine ( hypercalciuria ) causes nephrocalcinosis and kidney stones. Furthermore, provision of dysfunction in the proximal tubule to a aminoaciduria and increased potassium excretion that causes hypokalemia.

Nervous system

At birth, the children have a serious to very severe hypotonia, which may lead (muscle - self - reflection ) to an absence of deep tendon reflex. The hypotension may in turn lead to serious respiratory problems during the first period of life. Motor development is disrupted and the children develop the ability of independent walking generally after the age of three.

Approximately 10% of patients have a mild intellectual disability. However, in many cases it is moderate to severe with IQs below 50, the largest percentage of these (87% ) shows self-injury and hetero- aggressive behavior, irritability, and anger. Also obsessive-compulsive disorder are common. Approximately 50 % of patients over 18 years has epileptic seizures. Up to 9 % has febrile convulsions.

Genetics

The Lowe syndrome is caused by mutations in the gene OCLR1. This gene is located on the long arm of the X chromosome at locus q25 - q26. OCLR1 the gene consists of 24 exons and encodes the enzyme phosphatidylinositol -4 ,5- bisphosphate 5-phosphatase ( Inositol polyphosphate -5- phosphatase). This phosphatase belongs to the family of 5 - phosphatases of type II and usually located in the trans -Golgi network. Where it is needed for the polymerization of actin. It dephosphorylated in particular phosphatidylinositol -4 ,5- bisphosphate [PI (4,5) P2 ] to phosphatidylinositol -4- phosphate [PI (4) P].

Diagnosis

Based on the symptoms, a preliminary diagnosis can be made. Because of the extremely rare occurrence of the disease, medical laboratory confirmation of the diagnosis is appropriate in each case. Due to the heterogeneity of the allelic mutations in the gene OCRL1, prenatal DNA analysis can be performed only in families in which the mutation is known. The measurement of the activity of phosphatidylinositol -4 ,5- bisphosphate 5-phosphatase in cultured amniocytes is prenatal biochemical process which may be used for the diagnosis of Lowe syndrome.

Therapy

The Lowe syndrome is incurable. The treatment is symptomatic and includes, among other things, cataract surgery, glaucoma treatment, speech therapy and physiotherapy. Against the behavioral neuroleptics, stimulants, benzodiazepines, antidepressants (eg, serotonin reuptake inhibitors ) can be prescribed. With clomipramine, paroxetine and risperidone treatment good results were obtained.

Forecast

For most patients, the terminal renal failure or hypotension leads to premature death; typically between 30 and 40 years.

First description

The oculo - cerebro -renal syndrome was first described in 1952 by Charles Upton Lowe and colleagues as a syndrome with aciduria, decreased urea production, Hydrophthalmus and mental retardation.

Further Reading

  • JK Brooks, R. Ahmad: Oral anomalies associated with the syndrome of Lowe oculocerebrorenal: case report with multiple unerupted teeth and pericoronal radiolucencies. In: Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. Volume 107, Number 3, March 2009, pp. e32 - e35, ISSN 1528 - 395x. doi: 10.1016/j.tripleo.2008.11.023. PMID 19,217,010th (Review).
  • AC Ruellas, MM, Pithom including: Lowe syndrome: literature review and case report. In: Journal of orthodontics. Volume 35, Number 3, September 2008, pp. 156-160, ISSN 1465-3125. doi: 10.1179/146531207225022599. PMID 18,809,779th (Review).
  • MT Rodrigues Santos, MM Watanabe, among others: Oculocerebrorenal Lowe syndrome: a literature review and two case reports. In: Special care in dentistry: official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry. Volume 27, Number 3, 2007 May- Jun, pp. 108-111, ISSN 0275-1879. PMID 17,658,186th (Review).
  • M. Lowe: Structure and function of the Lowe syndrome protein OCRL1. In: Traffic. Volume 6, Number 9, September 2005, pp. 711-719, ISSN 1398-9219. doi: 10.1111/j.1600-0854.2005.00311.x. PMID 16,101,675th (Review).
  • M. Harrison, EW Odell, EC Sheehy: Dental findings in Lowe syndrome. In: Pediatric dentistry. Volume 21, Number 7, 1999 Nov-Dec, pp. 425-428, ISSN 0164-1263. PMID 10,633,515th (Review).
  • M. Addis, M. Loi, among other things: OCRL mutation analysis in Italian patients with Lowe syndrome. In: Human mutation. Volume 23, Number 5, May 2004, pp. 524-525, ISSN 1098-1004. doi: 10.1002/humu.9239. PMID 15,108,291th
  • G. Amirhakimi, MH Fallahzadeh, H. Saneifard: Lowe Syndrome: Report of a Case and Literature Review Letters. In: Iran J Pediatr. Volume 19, Number 4, 2009, pp. 417-420.
  • T. Menke, SM Gu including: Lowe syndrome - Clinical findings and evidence of a genetic mutation in a 4 year old boy. In: Pediatrics. Volume 146, number 2, pp. 125-128, doi: 10.1007/s001120050257
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