Successful Pregnancy in a Patient with L-Amino Acid Decarboxylase Deficiency: Therapeutic Management and Clinical Outcome.

Abstract

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare inherited disorder of biogenic amine metabolism presenting with developmental delay, hypokinetic movement disorders, hypotonia, and autonomic dysfunctions.1 We report on the successful pregnancy in a previously reported 26-year-old AADC patient with a mild phenotype (Table 1).2 Since the diagnosis at the age of 22, treatment with rotigotine, pyridoxine, and escitalopram resulted in a remarkable improvement of fluctuating muscular weakness, oculogyric crises, palpebral ptosis, balance, and gait.2 After, as consequence of behavioral disinhibition and reduced control of sexual impulses, rotigotine was replaced by a prolonged release formulation of pramipexole (up to 0.78 mg/day once a day). Selegine was added to improve diurnal fluctuation of motor symptoms (up to 7.5 mg/day after a very slow dose increasing). While MAO-inhibitors and SSRIs association is contraindicated in common neuropsychiatric disorders due to the risk of serotonin intoxication syndrome, their synergic effect may be exploited to magnify the residual enzymatic activity in the defect of serotonin synthesis, such as AADC deficiency. Compound heterozygous for the mutations p.Tyr37Thrfs*5 (c.105delC) and p.Phe237Ser (c.710 T>C) The pregnancy of our patient occurred naturally at the age of 26. Escitalopram was suspended to prevent the risk of low birth weight.3 Doses of pramipexole and selegiline could be decreased (Table 1) without obvious neurological worsening. No oculogyric crises or myoclonic jerks were observed, and limb rigidity, fatigability, and muscular weakness were well controlled. UPDRS-part III score did not change with respect the prepregnancy status (Table 1). Blood pressure remained below the normal range for the age. At the 31st week of gestation preeclampsia occurred. At the 38th week of gestation, a cesarean delivery (cardiac deceleration at cardiotocography) resulted in the birth of a vital (Apgar score 91 and 105) low birth weight (2.440 grams) and small (for gestational age) male newborn. The infant presented with transient tachypnea and hypoglycemia in the first day after birth. His growth was regular after the early introduction of artificial nursing. No significant health problems were observed in the following months. Pregnancy was previously reported in inherited neurotransmitter disorders with a less severe phenotype than AADC deficiency (35 women with autosomal dominant guanosine triphosphate cyclohydrolase 1 deficiency, one with dihydropterine reductase deficiency, and one with 6-pyrovoyl-tetrahydrobiopterin synthase deficiency).4, 5 The defect of monoaminergic neurotransmitters in AADC deficiency potentially impairs embryo-maternal interactions at preimplantation stages of early embryogenesis, which could be prevented by the treatment with drugs acting on dopaminergic axis.6 Efficacy and safety profile of pramipexole and selegiline during pregnancy and lactation are reported, in 24 and three women affected by Parkinson disease or restless legs syndrome, respectively.5, 7 Pramipexole was associated with spontaneous abortion in 3 cases (co-exposition with isotretinoin in one case) while selegiline was associated with a ventral septal defect in a twin newborn (co-exposition with L-DOPA/carbidopa and entacapone).5 The present case shows that in AADC deficiency: (a) fertility may be not impaired, (b) the course of pregnancy can be successfully managed in patients with mild phenotypes, and (c) low dosages of pramipexole and selegiline may have a good efficacy and safety profile during pregnancy. 1. Research project: A. Conception, B. Organization, C. Execution; 2. Statistical Analysis: A. Design, B. Execution, C. Review and Critique; 3. Manuscript Preparation: A. Writing of the first draft, B. Review and Critique. M.M.: 1A, 1B, 1C, 3A, 3B F.M.: 1B, 1C, 3A L.P.: 1A, 1B, 1C, 3A S.F.: 1A, 1B, 1C, 3A C.C.: 1C, 3B Cl.C.: 1C, 3B G.M.: 1A, 1B, 1C, 3B V.L.: 1A, 1B, 1C, 3A, 3B Ethical Compliance Statement: We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. The authors confirm that the approval of an institutional review board was not required for this work and that they have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Informed written consent was obtained from the patient for the publication of her clinical data. Funding Sources and Conflicts of Interest: None of the authors have anything to declare. Financial Disclosures for previous 12 months: None of the authors have anything to declare.