Aromatic l-aminoacid decarboxylase deficiency: Unusual neonatal presentation and additional findings in organic acid analysis

详细信息    查看全文

• 作者：Jose E. Abdenur ; Nico Abeling ; Norma Specola ; Lia Jorge ; Andrea B. Schenone ; Arno C. van Cruchten and Nestor A. Chamoles
• 关键词：Aromatic l-aminoacid decarboxylase ; AADC ; Organic acids ; Hypoglycemia ; Neurotransmitters ; Vanillactic ; Vanylpyruvic ; N-Acetyl-vanilalanine ; N-Acetyl-tyrosine
• 刊名：Molecular Genetics and Metabolism
• 出版年：2006
• 出版时间：January 2006
• 年：2006
• 卷：87
• 期：1
• 页码：48-53
• 全文大小：195 K

文摘

Aromatic l-aminoacid decarboxylase (AADC) deficiency is a neurotransmitter defect leading to a combined deficiency of catecholamines and serotonin. Patients are usually detected in infancy due to developmental delay, hypotonia, and extrapyramidal movements. Diagnosis is based on an abnormal neurotransmitter metabolite profile in CSF and reduced AADC activity in plasma. An elevation of vanillactic acid (VLA) has been described as the only abnormality detected in organic acid analysis (OA) of urine. We report a patient who presented in the neonatal period with lethargy, hypotonia, metabolic acidosis, and hypoglycemia. Blood ammonia, lactic acid, and acylcarnitines were normal, but OA of a urine sample showed a small increase of VLA, raising the suspicion of AADC deficiency. The patient was lost to follow-up until the age of 8 months, when he presented with dystonia, abnormal movements, oculogyric crises, and hypothermia. Repeat OA showed not only increased levels of VLA, but also increased vanilpyruvic acid (VPA), N-acetyl-vanilalanine (AVA) and N-acetyl-tyrosine (NAT). Neurotransmitter analysis in CSF showed increased vanilalanine (1200 nmol/L, ref < 100) with decreased levels of 5-hydroxy-indoleacetic acid (5-HIAA, <5 nmol/L; ref 152–462), homovanillic acid (HVA, 83 nmol/L; ref 302–845), and methoxy-hydroxy-phenyl-glycol (<5 nmol/L; ref 51–112). AADC activity in plasma was nearly undetectable. In the urine, low excretion of vanilmandelic acid (<0.3 μmol/mmol creat; ref 0.3–20) and 5-HIAA (0.9 μmol/mmol creat; ref 4–18), was found, but HVA was normal and dopamine even elevated. This contradictory phenomenon of hyperdopaminuria has been described earlier in AADC deficient patients. We postulate that VPA and AVA could originate from vanilalanine (through a transaminase and an acetylase respectively), while NAT could originate from tyrosine through an AA acetylase. This report expands the clinical presentation of AADC deficiency and adds new markers of the disease for OA analysis, improving detection of AADC deficient patients in general metabolic screening procedures.