Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: clinical presentation and follow-up of 50 patients.
OBJECTIVE
To assess the mode of presentation, biochemical abnormalities, clinical course, and effects of therapy in patients of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency.


BACKGROUND
LCHAD deficiency is a rare, autosomal recessive inborn error of fatty acid oxidation. Although case reports and small series of patients have been published, these may not give a true picture of the clinical and biochemical spectrum associated with this disorder. To improve the early recognition and management of this potentially lethal disorder, we have reviewed a large cohort of LCHAD-deficient patients.


METHODS
A questionnaire was sent to the referring physicians of 61 unselected patients with LCHAD deficiency diagnosed in our center. The standardized questionnaire requested information about the clinical signs and symptoms at presentation, the clinical history, family history, pregnancy, biochemical parameters at presentation, treatment, and clinical outcome.


RESULTS
Questionnaires on 50 patients (82%) were returned and included in this study. The mean age of clinical presentation was 5.8 months (range: 1 day-26 months). Seven (15%) of the patients presented in the neonatal period. Thirty-nine patients (78%) presented with hypoketotic hypoglycemia, the classical features of a fatty acid oxidation disorder. Eleven patients (22%) presented with chronic problems, consisting of failure to thrive, feeding difficulties, cholestatic liver disease, and/or hypotonia. In retrospect, most (82%) of the patients presenting with an acute metabolic derangement also suffered from a combination of chronic nonspecific symptoms before the metabolic crises. Mortality in this series was high (38%), all dying before or within 3 months after diagnosis. Morbidity in the surviving patients is also high, with recurrent metabolic crises and muscle problems despite therapy.


CONCLUSIONS
LCHAD deficiency often presents with a combination of chronic nonspecific symptoms. Early diagnosis is difficult in the absence of the classical metabolic derangement. Survival can be improved by prompt diagnosis, but morbidity remains alarmingly high despite current therapeutic regimes.
den Boer
Margarethe E J
ME
Department of Pediatrics Academic Medical Center, University of Amsterdam, the Netherlands.
Wanders
Ronald J A
RJ
Morris
Andrew A M
AA
IJlst
Lodewijk
L
Heymans
Hugo S A
HS
Wijburg
Frits A
FA
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency*; D017668:Age of Onset; D005260:Female; D005500:Follow-Up Studies; D017359:HELLP Syndrome / Q000453:epidemiology; D006306:Health Surveys; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000178:diet therapy / Q000453:epidemiology*; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D011247:Pregnancy; D017678:Sex Distribution; D011795:Surveys and Questionnaires; D015996:Survival Rate; D016896:Treatment Outcome
D015094:3-Hydroxyacyl CoA Dehydrogenases