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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT  
Year : 2020  |  Volume : 31  |  Issue : 1  |  Page : 285-288
Lowe syndrome – Case report with a novel mutation in the oculocerebrorenal gene


1 Department of Nephrology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
2 Department of Surgery, Fortis Hospital, Ludhiana, Punjab, India

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Date of Submission14-Dec-2018
Date of Acceptance15-Jan-2019
Date of Web Publication3-Mar-2020
 

   Abstract 


The oculocerebrorenal (OCRL) syndrome, also known as Lowe syndrome (LS), is an X-linked recessive disorder that predominantly affects males and is characterized by growth and mental retardation, congenital cataract and renal Fanconi syndrome. OCRL1 is the gene responsible for LS and encodes an inositol polyphosphate-5-phosphatase. We report a male child from North India, with LS with missense mutation in exon 14 of the OCRL gene.

How to cite this article:
Sethi S, Sethi N, Mehta S, Kaur S, Makkar V, Sohal P M. Lowe syndrome – Case report with a novel mutation in the oculocerebrorenal gene. Saudi J Kidney Dis Transpl 2020;31:285-8

How to cite this URL:
Sethi S, Sethi N, Mehta S, Kaur S, Makkar V, Sohal P M. Lowe syndrome – Case report with a novel mutation in the oculocerebrorenal gene. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2020 Apr 4];31:285-8. Available from: http://www.sjkdt.org/text.asp?2020/31/1/285/279955



   Introduction Top


In 1952, Lowe et al described a syndrome with organic aciduria, decreased renal ammonia production, hydrophthalmos, and mental retar- dation.[1] In 1954, a renal Fanconi syndrome was recognized as being associated with the syndrome,[2] and in 1965, an X-linked pattern of inheritance was determined.[3]

The oculocerebrorenal (OCRL, Lowe) syndrome is characterized by congenital cataracts, hypotonia, developmental delay, poor growth, and renal tubular dysfunction. Clinical problems typically include polyuria, acidosis, and hypophosphatemia with rickets and eventually, end-stage renal disease.[4]

Lowe syndrome (LS) is a rare disorder, the incidence of which is only a few cases per 100,000-500,000 births.[3] Most of the patients are asymptomatic at birth and the severity of the renal disease can vary among patients and this determines the overall prognosis.[4] The responsible gene, located at Xq26.1, is OCRL1, and it encodes a phosphatidylinositol-4, 5- biphosphate-5 phosphatase that is found in the Golgi complex.[3] A mutation in the OCRL1 gene locus, which contains 24 exons, causes this syndrome by a reduction in the contents of OCRL1 protein.


   Case Report Top


Informed consent was obtained from the responsible relatives of the patient for publication of this case report and accompanying images.

A 15-year-old boy born from a nonconsan- guineous marriage with the normal birth history presented with congenital bilateral cataract and delayed milestones. Later on, he developed psychomotor retardation, dysmor- phic facial features, behavioral disturbances (irritability), which progressively worsened. Later on, there was a change in gait followed by frequent falls and multiple fractures at four years of age. Renal impairment was detected at the age of six years.

On examination, he had frontal bossing, normally placed large ears, deep-set eyes, hyper- metropia, deformation of teeth, and enamel hypoplasia [Figure 1] and [Figure 2]. His height and weight were 3 standard deviation. Systemic examination showed pigeon-shaped chest with the prominence of costochondral junctions and Harrison sulcus present at the anterior aspect of chest, and he had 60% IQ with diminished deep tendon reflexes and tone was decreased in all the four limbs. Lower limbs were externally rotated and knock knee and genu valgus deformity were present. The presence of hypotonia, congenital cataract and features of renal rickets led to a high suspicion of LS in this patient.
Figure 1: Clinical photograph of the patient showing deformity in lower extremities.

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Figure 2: Facial appearance of the patient.

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On investigations, he had hemoglobin of 9.2 g/dL, total leukocyte count of 8200 with 69% polymorphs, and 8% lymphocytes. His blood urea was 87 mg, creatinine 1.8 mg, serum calcium 8.2 mg/dL, serum phosphorous 3.6 mg/dL, and liver function tests were normal. Arterial blood gas analysis showed normal anion gap metabolic acidosis. Urine routine analysis showed pH 6.0, specific gravity 1.01, sugar +1, and protein +2. Genetic analysis showed normal karyotyping. His urinary biochemical parameters revealed elevated alanine 7076 μmol/L, citrulline 720 μmol/L, lysine 2500 μmol/L, with positive for cysteine and tyrosine.

Brain magnetic resonance imaging of the patient demonstrated white matter abnormalities, particularly in the periventricular area [Figure 3]. Radiographs of the wrists and long bones demonstrated changes that are typical of rickets, including metaphyseal splaying and fraying and osteopenia [Figure 4] and [Figure 5]. His treatment included cataract extraction and physical and speech therapy. He was given drugs which addressed his behavioral problems, correction of the renal tubular acidosis, and consequent bone diseases. Missense mutation (c.1427C>T) in exon 14 of the OCRL gene was observed in our patient.
Figure 3: Lacunar lesions and bilateral periventricular leukomalacia on T2-weighted magnetic resonance imaging.

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Figure 4: Fraying and spraying pattern seen on X-ray of the hands.

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Figure 5: Tri-radiate pelvis seen on X-ray.

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   Discussion Top


Diagnosis of the OCRL syndrome, namely LS, is based on specific ophthalmologic, neurologic, and renal abnormalities.[5],[6] Cataract is an important finding among all clinical features. It develops in utero and is caused by altered migration of the crystalline embryonic epithelium.

Neurological features of the LS include developmental delay, hypotonia, seizures, areflexia, cognitive impairment, behavioral disturbances, and abnormal findings in brain imaging studies, such as brain atrophy, delayed myeli- nation, pachygyrias, and hydrocephalus.[7],[8],[9]

The renal findings of LS include low- molecular-weight proteinuria, hypercalciuria, hematuria, hyperuricosuria, glycosuria, metabolic acidosis due to proximal tubular bicarbonate wasting, and hypophosphatemia due to renal phosphate wasting.[10] These findings may be associated with renal rickets, osteomalacia, and pathological fractures. It is known that the severity of renal disease in LS changes from asymptomatic to renal Fanconi syndrome and even chronic renal failure.[4] Not all the features of renal Fanconi syndrome, but rather selective tubular dysfunction findings, are expected in the LS. In a series of patients with genetically proven LS, low-molecular-weight proteinuria, and albuminuria were the prominent findings, although none had glycosuria and only some had generalized aminoaciduria, tubular phosphate loss and rickets, hypercalciuria, or nephrocalcinosis.[11]

In our case, tubular proteinuria was the prominent renal finding. He had dental findings and severe osteoporosis suggestive of rickets with a history of treatment for rickets. As a result, we may consider that our patient had a severe form of renal tubular defect.

Our patient had motor and mental retardation, and an IQ of 60, with a history of hypotonia. Diagnosis of OCRL is based on specific ophthalmologic, neurologic, and renal abnormalities. Cataract is an important finding among all clinical features. A history of cataract surgery in early childhood provided an important clue for the diagnosis of LS in our patient. He had renal tubular defect which supports the diagnosis.

Clinical findings are adequate for the diagnosis of LS; however, genetic analysis is necessary for genetic counseling. The responsible gene is located on the long (q) arm of the X chromosome at position 26.1. The OCRL1 gene provides instructions for making an enzyme that is present in cells throughout the body. More than 120 mutations in the OCRL1 gene have been identified in individuals with LS.

Conflict of interest: None declared.



 
   References Top

1.
Alp H, Alp E, Pirgon O, Atabek ME, Peru H. Ricketsial findings: Presenting as features of oculocerebrorenal syndrome (Lowe syndrome): Case report. Turk Klin J Pediatr 2009;18:244- 7.  Back to cited text no. 1
    
2.
Gropman A, Levin S, Yao L, et al. Unusual renal features of Lowe syndrome in a mildly affected boy. Am J Med Genet 2000;95:461-6.  Back to cited text no. 2
    
3.
Bickel H, Thursby-Pelham DC. Hyperamino- aciduria in Lignac-Fanconi disease, in galac- tosaemia and in an obscure syndrome. Arch Dis Child 1954;29:224-31.  Back to cited text no. 3
    
4.
Bockenhauer D, Bokenkamp A, van’t Hoff W, et al. Renal phenotype in Lowe syndrome: A selective proximal tubular dysfunction. Clin J Am Soc Nephrol 2008;3:1430-6.  Back to cited text no. 4
    
5.
Cho HY, Lee BH, Choi HJ, Ha IS, Choi Y, Cheong HI. Renal manifestations of dent disease and Lowe syndrome. Pediatr Nephrol 2008;23:243-9.  Back to cited text no. 5
    
6.
Erdogan F, Ismailogullari S, Soyuer I, Ferahbas A, Poyrazoglu H. Different seizure types and skin lesions in oculocerebrorenal syndrome of Lowe. J Child Neurol 2007;22: 427-31.  Back to cited text no. 6
    
7.
Lin T, Orrison BM, Leahey AM, et al. Spectrum of mutations in the OCRL1 gene in the Lowe oculocerebrorenal syndrome. Am J Hum Genet 1997;60:1384-8.  Back to cited text no. 7
    
8.
Lin T, Orrison BM, Suchy SF, Lewis RA, Nussbaum RL. Mutations are not uniformly distributed throughout the OCRL1 gene in Lowe syndrome patients. Mol Genet Metab 1998;64:58-61.  Back to cited text no. 8
    
9.
Lowe CU, Terrey M, MacLACHLAN EA. Organic-aciduria, decreased renal ammonia production, hydrophthalmos, and mental retardation; a clinical entity. AMA Am J Dis Child 1952;83:164-84.  Back to cited text no. 9
    
10.
Richards W, Donnel GN, Wilson WA, Stowens D, Perry T. The oculocerebral syndrome of Lowe. Am J Dis Child 1965;109: 1854-203.  Back to cited text no. 10
    
11.
Satre V, Monnier N, Berthoin F, et al. Characterization of a germline mosaicism in families with Lowe syndrome, and identification of seven novel mutations in the OCRL1 gene. Am J Hum Genet 1999;65:68- 76.  Back to cited text no. 11
    

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Correspondence Address:
Sudhir Mehta
Department of Nephrology, Dayanand Medical College and Hospital, Ludhiana, Punjab
India
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DOI: 10.4103/1319-2442.279955

PMID: 32129227

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]



 

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