Prevalence of lysosomal storage disorders in Australia from 2009 to 2020

Abstract

Background Lysosomal storage disorders (LSD) are a family of genetic diseases that have a devastating impact on the patient and family with a concomitant health burden. Although considered rare disorders, improved diagnostic capabilities, newborn screening programs and public awareness has witnessed the frequency of many LSD increase considerably over recent years. To quantify their footprint, the number of LSD diagnosed in the multicultural Australian population in a 12-year period was determined. The principle objective was to yield contemporary prevalence figures to inform public health policies.Methods From the national referral laboratory for LSD diagnoses in Australia, retrospective data from patient referrals and prenatal testing for the period January 1 2009 to December 31 2020 were collated. Diagnosis was established biochemically by enzyme activity and/or metabolite determinations, as well as molecular genetic testing. The incidence of each disorder was determined by dividing the number of postnatal diagnoses by the number of births with prevalence including prenatal diagnoses.Findings During this 12-year period 766 diagnosis of LSD were confirmed inclusive of 32 prenatal outcomes representing 38 individual disorders. Total diagnosis per 100,000 live births averaged 21 per year (range 16 − 26) with Fabry disease the most prevalent representing 34% of all diagnoses in the current (up to 2020) report.Interpretation The combined prevalence of LSD for this study period at 1 per 4,800 live births is considerably higher than 1 per 7,700 reported for a 17-year period up to 1996. Additionally, more adults were diagnosed than children, implying that LSD are more common in adulthood than childhood. These data highlight the requirements for physicians to consider LSD in symptomatic adults and should refigure public health policies steering newborn screening programs in the direction of adult-onset conditions.

Consensus clinical management guidelines for acid sphingomyelinase deficiency (Niemann–Pick disease types A, B and A/B)

“…In part, this may be due to founder effects and the incidence of consanguinity. In addition, most of these estimates are based on data from lysosomal storage disease testing laboratories rather than from population-based screening [18][19][20][21]. More accurate determination of the true disease incidence must await additional screening data in different populations.…”

Advances in therapies for neurological lysosomal storage disorders

“…Of the approximately 70 monogenic LSDs described to date, the majority follow an autosomal recessive inheritance pattern, with the exception of three X‐linked disorders: Mucopolysaccharidosis (MPS) type II, Fabry and Danon disease. In isolation, individual LSDs are rare, however, combined they account for an overall prevalence reported to be as common as 1 per 4800 live births, depending on geographical location 3–6 . In addition to this, a greater number of adults are diagnosed compared to children, suggesting that LSDs are more common in adulthood 5 …”

“…In isolation, individual LSDs are rare, however, combined they account for an overall prevalence reported to be as common as 1 per 4800 live births, depending on geographical location. [3][4][5][6] In addition to this, a greater number of adults are diagnosed compared to children, suggesting that LSDs are more common in adulthood. 5 Clinical manifestations of LSDs can be extremely variable depending on the type of the storage material and physical distribution throughout the body.…”

“…In isolation, individual LSDs are rare, however, combined they account for an overall prevalence reported to be as common as 1 per 4800 live births, depending on geographical location 3–6 . In addition to this, a greater number of adults are diagnosed compared to children, suggesting that LSDs are more common in adulthood 5 …”

Repurposing Dipyridamole in Niemann Pick Type C Disease: A Proof of Concept Study

“…Niemann Pick type C (NPC) disease is a genetic disorder with an estimated incidence of ~1:100,000 [ 1 , 2 ]. It can be caused by mutations in either the NPC1 (95% of the cases) or NPC2 genetic locus; the NPC1 protein is located in the membrane of late endo/lysosomes (LE/L) while NPC2 is a soluble endo/lysosomal protein acting in sequence with NPC1 to bind and transport cholesterol out of the LE/L compartment [ 3 ].…”