DELAYED NEUROMOTOR DEVELOPMENT COMBINED WITH ALBINISM AND INCREASED VERY LONG CHAIN FATTY ACIDS

Objectives: A five-week-old girl was referred to the hospital because of feeding difficulties, hepatomegaly, and oculocutaneous albinism. Transaminases in the blood were increased. Results: She was born as second child of healthy parents. No problems were reported until the age of five weeks, when she started to drink less well and sleep more. She was a pale, hypotonic baby with white hair, horizontal nystagmus and hepatomegaly. Routine blood tests showed increased AST, ALT, alkaline phosphatase (AP) and lactate dehydrogenase (LDH). Ultrasound investigation demonstrated hepatomegaly without structural abnormalities and normal size of the spleen. Cranial CT scan was normal. Griscelli syndrome was ruled out because specific granulations in the hair were not found and because of normal chemotaxis and natural killer activity. Normal bleeding time and normal clothing parameters made Chediak-Higashi syndrome less likely. She is carrier of a nonsense mutation in the p-gene. All the other genes associated with isolated albinism, such as tyrosinase, Tyrp1 and MATP were normal. Metabolic screening demonstrated increased very long chain fatty acids in serum. Electron microscopy of the skin showed melanocytes with empty, irregularly shaped melanosomes. She is now seven months old, and has a mildly delayed neuromotor development and hypotonia. Although AST, LDH, AP and LDH normalized, very long chain fatty acids remained increased, suggestive for a peroxisomal defect.

Conclusion: Our hypothesis is that this girl has a disorder in intracellular vesicle function leading to defective melanosomes, peroxisomes and possibly also defective neurotransmitter release in the brain leading to delayed development and hypotonia. Liver biopsy and peroxisomal studies on cultured fibroblasts are currently going on.