Zuriat Case Summary

By Prof. Zabidi Hussin

MM is a 21 yrs old lady youngest of 5 children and the only survivor in her family. All 5 children in this family has Juvenile Onset Metachromatic Leukodystrphy (a fatal degenerative white matter disorder) Diagnosis on was first made on MMs eldest sister at age 9 yrs old when she presented with psychiatric symptoms. Subsequently the second child, at age 9 yrs, developed unsteadiness. MRI showed the same disease as her sister (eldest). At that time other 3 siblings were asymptomatic Blood and urinary analysis were done on all family members in Australia with help of an external examiner who volunteered to bring specimens to Australian center. No other centers in the South Asian region offer the test. The disease was confirmed in all 5 siblings, including the 3 who were asymptomatic. Symptoms usually appear at 9yrs and rapidly degenerate. Death usually occurs within 5 years. Literature review brought into picture experimental therapies in USA for asymptomatic cases. Bone Marrow Transplant (BMT) has been tried with varying success. At that time MM was 6 yrs old, elder symptomatic siblings were 7 and 8 yrs respectively. The challenge was for the 6 and 7 yrs old (MM and her older brother) to undergo an experimental therapy. The other child went on to develop the symptoms at 9yrs and died at 15 yrs old. Malaysian Medical Board disapproved therapy due to the expensive cost. Malaysian public was made aware of plight of children. Massive media campaign was launched to get donation. Workup for BMT was done, but no matching donors were found. The closest potential donor was a 4 of 6 matched HLA in Australian Stem Cell Bank. 18 months were lost trying to justify funding to USA and convincing Malaysian government to provide funding. But the campaign was successful. MM and elder sibling were sent to USA in 1996 for matched-unrelated BMT, an experimental procedure with high risk. MMs sibling (older brother) died post BMT from fungal infection. MM stayed in USA for 6 months, returned home with severe graft versus host disease but survived all complications. MM is currently disease-free but has cataracts (intraocular lenses), neural deafness (hearing aid), has not achieved puberty at 21 yrs, has secondary ovarian failure and chronic lung disease with occasional break through infections. MM now in college studying culinary studies and due to graduate in 6 months. She is fully cured from MLD