Lowe Syndrome – Clinician Information

Childhood management guidelines for nephrologists.

  • Overview and clinical features
    • Lowe Syndrome is a rare X-linked recessive syndrome, thus affecting boys. Key organs affected are the eyes, brain and kidneys (Oculo-Cerebro-Renal syndrome of Lowe). However, clinical forms affecting only one or two organ systems have been described. If only the kidneys are affected, the clinical phenotype copies that of Dent Disease (for more information, see Dent Disease).
    • Lowe Syndrome is caused by partial or complete loss of function of the phosphatase OCRL, which is involved in intracellular trafficking.
    • Ocular manifestations include cataracts and glaucoma. Most patients first come to medical attention by the discovery of cataracts in the neonatal period.
    • Neurological manifestations typically include muscular hypotonia and hyporeflexia, developmental delay and learning disabilities. In addition, behavioural abnormalities (temper tantrums, negativism, repetitive and obsessive behaviours) and seizures can be seen.
    • Renal manifestations are initially dominated by a proximal tubulopathy: low-molecular weight proteinuria is virtually always present as early as the neonatal period and thus constitutes a good screening tool for patients in whom a diagnosis of Lowe Syndrome is considered. Hypercalciuria is present in most patients and may result in nephrocalcinosis and/or stones. Metabolic acidosis and hypophosphataemic rickets are often seen, whereas glycosuria is rarely present.
    • GFR is initially normal or only mildly impaired, but typically declines with age and most patients reach ESKD in the fourth to fifth decade.
    • Other clinical features can include: growth failure, platelet dysfunction with prolonged bleeding, arthropathy (usually seen only in adolescent or adult patients), cryptorchidism and benign skin tumors such as vellus hair cysts. Rickets can be a consequence of the tubulopathy.
  • Diagnosis
    • Lowe Syndrome should be suspected in any newborn boy with cataracts and muscular hypotonia.
    • Renal involvement can be confirmed by testing the urine for low-molecular weight proteins, such as retinol-binding protein (RBP).
    • Mutations in the underlying gene OCRL are found in approximately 90% of patients with a clinical diagnosis of Lowe Syndrome. Details for testing in the UK can be found here.
  • Management
    • There is no specific treatment for Lowe Syndrome.
    • Clinical management involves coordinated care between the various specialities.
    • Patients should be screened routinely (with frequency depending on symptoms) for above clinical features, including biochemical abnormalities, such as acidosis, hypophosphataemia and hyperparathyroidism. Renal US can identify nephrocalcinosis and/or stones.
    • Since 1-alfa hydroxylation of vitamin D occurs in the proximal tubule, patients often need supplementation with 1-alfa calcidol, adjusted to plasma PTH levels. Oversupplementation may worsen the nephrocalcinosis.
    • In patients with metabolic acidosis and/or hypophosphataemia, appropriate supplementation should be given. Citrate (metabolized to bicarbonate) can provide alkali and may ameliorate urinary calcium precipitation.
    • Tranexamic acid may ameliorate the platelet dysfunction and should be considered in patients with prolonged bleeding and prior to surgical interventions. Advice from a haemostasis expert is recommended.
    • Supplemental feeding may be needed in some patients with failure-to-thrive.
  • Further Information
Lowe Syndrome Clinician Information Version 5 updated June 2017
Written by the Dent Disease & Lowe Syndrome Rare Disease Group