There had been increased and strong public interests in rare diseases and orphan drugs as well as the issue of
compulsory licencing for expensive medications in Malaysia in the mass-media and social media. We reviewed
the issues of orphan drugs and the challenges faced in many countries in developing appropriate health financial
modelling as well as getting accurate data on rare diseases. We also reviewed the old off-patent medications
and the developments on how policy-makers can intervene to make expensive treatment affordable and
sustainable for patients and the country.
Inborn errors of metabolism (IEM) are a group of disorders that causes abnormal function of biochemical pathways. Archibald Garrod des-cribed the first inborn error of metabolism in 1893. He described alkaptonuria in a patient whose urine turned black on standing and the development of arthritis in adult life.' Subse-quently, Garrod encapsulated the idea of IEM in 1908 with the concept of 'chemical indivi-duality'. Beadle and Tatum proposed the concept of one gene - one enzyme in 1945.2 Phenyl-ketonuria (PKU) was described in 1934 and amongst the first to be recognised as a cause of mental handicap with a biochemical basis.' Effective treatment for PKU with low pheny-lalanine diet was introduced in 1955. Molecular characterisation of genetic defects localised to alleles in various chromosomes were performed in the last two decades
We report the first known ethnic Malay patient with laminin alpha-2 (merosin) deficiency (MDC1A),
a subtype of congenital muscular dystrophy (CMD)as a result of novel LAMA2 gene mutations. The
21-month-old female presented with hypotonia at birth and gross motor delay of her distal lower
limbs. Physical examination showed generalised hypotonia, hyporeflexia and myopathic facies but
good cognitive functions. Serum creatine kinase was elevated and white matter changes were detected
in the brain MRI. Muscle biopsy showed dystrophic changes with complete laminin α2 deficiency
by immunohistochemistry. Mutation analysis of LAMA2 showed compound heterozygote at exon 21,
c.2888delG(p.Gly963Alafs*111) and exon 34, c.4886dupC(p.Pro1629Profs*40) leading to premature
stop codon for each of the frameshift mutations. Patient review at seven years of age showed satisfactory
cognitive functions despite having contractures and weakness. Genetic testing of LAMA2 related
muscular dystrophy facilitated the earlier diagnosis of MDC1A and genetic counselling for this family.