Early treatment with laronidase improves clinical outcomes in patients with attenuated MPS I: a retrospective case series analysis of nine sibships.

BACKGROUND: Enzyme replacement therapy (ERT) with laronidase, (recombinant human α-L-iduronidase; Aldurazyme) is the primary treatment option for patients with attenuated mucopolysaccharidosis type I (MPS I). This study examined the effect of early ERT on clinical manifestations. METHODS: This multinational, retrospective case series abstracted data from records of 20 patients with Hurler-Scheie syndrome within nine sibships that included older siblings treated with laronidase after the development of significant clinical symptoms, and younger siblings treated before significant symptomatology. Median age at diagnosis was 5.6 and 0.5 years for older and younger siblings, respectively. Median age at ERT initiation was 7.9 and 1.9 years for older and younger siblings, respectively. RESULTS: Improvement or stabilization of somatic signs and symptoms was more notable in younger siblings. Organomegaly present at onset of ERT improved in the majority of both older and younger siblings. Analysis of physician-rated symptom severity demonstrated that cardiac, musculoskeletal, and cognitive symptoms, when absent or mild in younger siblings at ERT initiation, generally did not develop or progress. The majority of older siblings had height/length Z-scores greater than two standard deviations below the mean (less than -2) at both time points. In general, Z-scores for younger siblings were closer to the sex- and age-matched means at follow-up. CONCLUSIONS: These findings suggest early initiation of laronidase, prior to the onset of symptoms in patients with attenuated MPS I, can slow or prevent the development of severe clinical manifestations.

Hyperoxaluria and rapid development of renal failure following a combined liver and kidney transplantation: emphasis on sequential transplantation.

Primary hyperoxaluria type I (PH I) is a rare genetic disorder that leads to end stage renal disease (ESRD) at an early age due to excessive deposition of calcium oxalate in the kidney. Combined liver-kidney transplantation (LKTx) has been advocated as the treatment of choice for patients with PH I who have progressive renal disease. With combined LKTx the risk of early renal failure secondary to oxalate deposition is anticipated. Here we report a patient with PH I who developed ESRD and underwent a combined LKTx. He lost the kidney graft secondary to early recurrence of oxalosis. Repeat kidney transplantation 13 months after the initial procedure was successful. Elevated plasma oxalate levels persisted for a long time following LKTx and lead to further deposition of oxalate in the second kidney graft. Combined LKTx for patients with PH I requires meticulous preparation and very careful post operative management. Sequential liver transplantation followed by kidney transplantation is to be considered for PH I patients who have ESRD and very high oxalate load.

Carnitine-acylcarnitine translocase deficiency. Clinical course of three Saudi children with a severe phenotype.

Carnitine-acylcarnitine translocase (CACT) deficiency (McKusick 212138) is a rare life threatening disorder characterized by hypoketotic hypoglycemia, hyperammonemia, encephalopathy, cardiomyopathy hepatopathy, and myopathy. Here, we present a detailed clinical course of 3 Saudi siblings with a severe phenotype. The third patient was described in more detail. Early medical intervention in the form of 25% dextrose intravenous infusion and carnitine supplement followed by a gradual introduction of a high carbohydrate low fat special formula resulted in a good clinical and biochemical response to the treatment in our patient. However, early nephrocalcinosis, severe hypotonia, and subsequently intravascular cerebral accident could not be prevented. He died at 18 months of age as a result of metabolic decompensation. This suggests that CACT deficiency is still a lethal disorder even with an early and aggressive medical intervention.