Case of the Week
Section Editors: Matylda Machnowska1 and Anvita Pauranik2
1University of Toronto, Toronto, Ontario, Canada
2BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
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September 29, 2016
Lowe (Oculocerebrorenal) Syndrome
- Background:
- X-linked recessive multisystem disorder due to OCRL1 gene mutation and primarily affecting the brain, eyes, and kidneys
- Clinical Presentation:
- Boys present with hypotonia at birth.
- Congenital cataract is common. Glaucoma may develop in up to 50% of patients after the first year of life.
- Progressive proteinuria, hematuria, and varying degrees of renal impairment (Fanconi renotubular syndrome)
- Rickets, bone fractures, and scoliosis
- Motor and mental retardation are also frequent in these patients.
- Key Diagnostic Features:
- CT brain: normal initially; dense/calcified lenses secondary to development of cataract
- MRI brain: delayed myelination in the neonatal period; progressive development of characteristic dilated perivascular spaces in the subcortical and periventricular white matter with surrounding gliosis
- MR spectroscopy: not definitive for the diagnosis, but abnormally elevated myo-inositol peak (3.56 pm) may occur as a result of gliosis from brain tissue injury or phosphatidyl inositol 4,5-biphosphate accumulation, due to loss of function of the OCRL1 protein of Lowe syndrome
- Differential Diagnoses:
- Mucopolysacharridosis (MPS): Numerous dilated perivascular spaces are seen with predilection for the peritrigonal white matter and the corpus callosum. These patients usually have the typical coarse facial features.
- Congenital myotonic dystrophies (CMD): Subcortical cerebellar cysts are seen with Fukuyama congenital muscular dystrophy phenotype and Muscle-Brain-Eye phenotype. There are many other associated abnormalities including polymicrogyria, cobblestone cortex, and delayed myelination. Clinical features include hypotonia at birth, delayed motor skills, and congenital eye disease (cataracts, glaucoma, myopia, and retinal detachment).
- Congenital CMV: Intracranial calcifications in the periventricular regions, diffuse white matter volume loss with ventriculomegaly, germinolytic periventricular cysts (most often in the temporal poles), and cerebellar hypoplasia are hallmarks of this disease. Clinically, patients present with microcephaly, seizures, hypotonia/hypertonia, and sensorineural hearing loss.
- Hypomelanosis of Ito: Dilatation of perivascular spaces with surrounding gliosis may be present. Other features include cortical dyplasias, hemimegalencephaly, and polymicrogyria. Patients present with characteristic skin abnormalities and may have involvement of multiple organ systems. Neurologic manifestations include mental retardation and epilepsy.
- Treatment:
- There is no cure for Lowe syndrome.
- The diagnosis is made with a skin biopsy or blood test to determine the gene mutation, and most patients have cataract surgery.
- Dietary recommendations are soon started to reduce calcium excretion and avoid renal osteodystrophy.
- Patients are also offered oral phosphate therapy to improve bone disease, and renal dialysis or kidney transplant may be needed as the disease progresses.
- Life expectancy is approximately 30-40 years if no fatal complications occur.
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