Inherited Neuroendocrine Peroxisomal Disorder Involving Abnormal Very Long Chain Fatty Acids Metabolism: Long-Term Follow up after Allogeneic Bone Marrow Transplant

Presentation Number: SAT-0748
Date of Presentation: June 21st, 2014

Mohammed Ahmed*
King Faisal Spec Hosp/Res Ctr, Riyadh, Saudi Arabia

Abstract

Introduction

Adreanleukodystrophy(ALD) is X-linked disorder of peroxisomal fatty acid ß-oxidation resulting in abnormal accumulation of very long chain fatty acids (VLCFA). It is caused by mutations in ABCD1 gene, located at Xq28, that encodes ABC transporter. The  transporter helps transloate VLCFA into the peroxisome. ABCD1 mutations prevent normal transport of VLCFA into peroxisomes, thereby preventing  ß-oxidation. ALD is a heterogamous disorde.The most severely affected tissues are adrenal cortex , testicular Leydig cells & myelin in CNS. ACTH levels are often increased during early life. VLCFA levels are elevated in 99.9% males w/ ALD of all ages . The parameters analyzed are: concentration of C26:0,C 24:0, ratio of C26:0/C22:0 & C24:0/C22:0.

Objective:I present an asymptomatic familial case diagnosed early in life w/ adrenal insufficiency & early brain abnormalities detected on MRI. Definitive treatment using bone marrow transplant (BMT) was instituted. Long-term FU revealed arrest of disease process associated w/ substantial decline in levels of VLCFA , regression of abnormal brain MRI findings, & preserved testicular function.  

Case Report: A 2-yr. old asymptomatic male had lost 2 brothers from ALD. Pt. was 10th percentile for height & weight, had no history of seizure disorder, had normal  neurological, ophthamological, & audiolgy findings . Lab findings: Normal EEG, serum AM cortisol 239 nmol/l, (RR: 170-356), elevated serum AM ACTH 144 ng/l (RR: 5-60 ng/l), & abnormal synacthen test. GC/MS analysis repeated x2 revealed abnormally increased  VLCFA profile  (values expressed in ug/ml) C26:0 1.406 (RR: 0.256+/- 0.08), C24:0: 12.45:(RR:0.12+/- 0.01), an abnormal ratio for VLCFA/LCFA profile: C26/C22: 0.248 (RR: 0.019+/- 0.007), C24/C22: 2.196. MRI Brain: minimal increased signal intensity involving bilateral peritrigonal regions  consistent w/ early changes of ALD but findings had progressed a year later.

Clinical Course: Treatment consisted of Hormonal replacement using hydrocortisone & florinef, followed later using allogeneic BMT. Serum VLCFA improved w/ C26 declining to 0.544. MRI brain done 2 years post BMT showed substantial improvement & no additional lesions seen compared to previous year. At age 15 years pt. developed normal puberty w/ serum testosterone of 23.67 nmol/l (RR: 9.9-27.8), normal LH & FSH. However, pt. has developed Nelson’s syndrome, serum ACTH increased to 248, & MRI showed 7x 4 mm centrally located lesion. A progressive increase in ACTH level to 2594 warranted  increase in hyrdocortisone dose to 5 mg tid w/ a decline in ACTH to 29.   

Conclusions: A combination of classical clinical features coupled w/ abnormal plasma levels of VLCFA  is sufficient to establish the Dx of X-ALD. ACTH levels are often increased  during early life, & should alert to early Dx. Definitive treatment using bone marrow transplant offers a promising approach towards disease arrest.

 

Nothing to Disclose: MA