Surgical management of superficial digital flexor tendon luxation in dogs: 48 cases (2005-2020).

OBJECTIVES: To report the outcome, frequency of complications and potential prognostic factors associated with surgical repair of superficial digital flexor tendon (SDFT) luxation in dogs. MATERIALS AND METHODS: Medical records from 10 referral hospitals were reviewed retrospectively for cases of SDFT luxation in dogs that underwent surgical stabilisation. Signalment, clinical presentation, diagnostic imaging, surgical method, type and length of post-operative limb immobilisation, nature of and length of exercise restriction, presence of post-operative complications and outcomes were recorded. Data were summarised descriptively and prognostic risk factors assessed for association with surgical outcome using risk ratios. RESULTS: Forty-eight cases were included. A successful surgical outcome was recorded in 35 of 48 (73%) cases. Re-luxation of the SDFT occurred in seven of 48 (15%). Six out of 48 (13%) had a persistent lameness despite a stable non-luxating SDFT. A high frequency of post-operative complications occurred (71%), with the majority resolved medically. The risk of surgical failure was 60% higher (risk ratio 1.6, 95% confidence interval 1.1 to 2.4) where absorbable suture material was used compared to non-absorbable suture material. Surgical failure was more common in cases managed with non-rigid immobilisation post-operatively (57% failure) compared to cases managed with rigid immobilisation (19% failure), although this result was not statistically significant. Limb immobilisation of 6 weeks or longer did not significantly affect surgical outcome, compared to shorter periods of exercise restriction or limb immobilisation. CLINICAL SIGNIFICANCE: A good outcome can be expected following surgical stabilisation of SDFT luxation. The use of non-absorbable suture was associated with a more successful surgical outcome.

Long-term clinical outcomes following surgery for spontaneous pneumothorax caused by pulmonary blebs and bullae in dogs - a multicentre (AVSTS Research Cooperative) retrospective study.

OBJECTIVES: To report the clinical characteristics and recurrence rate of spontaneous pneumothorax secondary to pulmonary blebs and bullae following surgical management in a large cohort of dogs. To explore potential risk factors for recurrence and describe outcome. MATERIALS AND METHODS: Medical records were retrospectively reviewed for cases with spontaneous pneumothorax managed surgically between 2000 and 2017. Signalment, clinical presentation, diagnostic imaging, surgery, histopathology findings and patient outcomes were recorded. Follow-up was performed via patient records and telephone contact. RESULTS: Records of 120 dogs with surgically treated pneumothorax were identified and reviewed, with 99 cases appropriate for exploratory statistical analysis. Median follow-up was 850 days (range: 9-5105 days). Two- and 5-year survival rates were 88.4% and 83.5%, respectively. There was recurrence in 14 of 99 dogs (14.1%) with adequate follow-up, with a median time to recurrence of 25 days (1-1719 days). Univariable Cox regression analysis suggested increased risk for recurrence in giant breeds (hazard ratio = 11.05, 95% confidence interval: 2.82-43.35) and with increasing bodyweight (HR = 1.04, 95% confidence interval: 1.00-1.09). Of 14 dogs with recurrence, six were euthanased, two died of causes related to pneumothorax and six underwent further treatment, of which five were resolved. CLINICAL SIGNIFICANCE: Long-term survival for dogs with surgically managed spontaneous pneumothorax was good and associated with a low risk of recurrence. Giant breed dogs and increased bodyweight were the only variables identified as possible risk factors for recurrence. The outcome for dogs with recurrence undergoing a second intervention was also favourable.

Child, Maternal and Demographic Factors Influencing Caregiver-Reported Autistic Trait Symptomatology in Toddlers.

Current research on children's autistic traits in the general population relies predominantly on caregiver-report, yet the extent to which individual, caregiver or demographic characteristics are associated with informants' ratings has not been sufficiently explored. In this study, caregivers of 396 Singaporean two-year-olds from a birth cohort study completed the Quantitative Checklist for Autism in Toddlers. Children's gender, cognitive functioning and birth order, maternal age, and ethnic group membership were not significant predictors of caregiver-reported autistic traits. Poorer child language development and higher maternal depressive symptoms significantly predicted more social-communicative autistic traits, while lower maternal education predicted more behavioural autistic traits. Children's language and informants' educational level and depressive symptomatology may need to be considered in caregiver-reports of autistic traits.

Safety and efficacy of warfarin in patients with moderate thrombocytopenia.

INTRODUCTION: Patients with moderate thrombocytopenia and comorbidities requiring anticoagulation are currently sub-optimally treated because of bleeding concerns. Guidance on anticoagulating such patients is currently lacking because of limited data on safety and efficacy of anticoagulation in such patients. METHODS: This retrospective study compared the incidence of bleeding and thrombosis in a cohort of warfarinized patients with sustained platelet counts below 100×109/L against a cohort with normal platelet counts (>140×109/L). Primary outcomes of safety and efficacy were determined by incidence rate ratios (IRR) of bleeding and thrombotic events. International normalized ratio (INR) and platelet counts during adverse events in thrombocytopenic arm were secondary outcomes. RESULTS: 137 thrombocytopenic patients (104,985 patient-exposure days) were compared against 939 normal patients (715,193 patient-exposure days). IRR of minor, major bleeding and thrombosis among thrombocytopenic patients were 3.03 (95% CI: 1.57-5.60), 1.48 (95% CI: 0.44-3.98), and 0.807 (95% CI: 0.09-3.43) respectively. Median INR and platelet count readings during minor and major bleeds were 3.60 (IQR: 2.70-4.12) and 3.12 (IQR: 2.82-4.22), and 99×109/L (IQR: 77.0-147.0×109/L) and 115×109/L (IQR: 107.5-169.5×109/L) respectively. CONCLUSION: Warfarinized thrombocytopenic patients are at higher risk of minor bleeding complications with a higher tendency for major bleeding but derive similar benefits against thrombotic events compared to normal patients. Bleeding events are associated with higher INRs. A narrow INR target with an upper limit below 2.5 together with closer anticoagulation monitoring may improve safety of patients.

Donor and host photoreceptors engage in material transfer following transplantation of post-mitotic photoreceptor precursors.

Photoreceptor replacement by transplantation is proposed as a treatment for blindness. Transplantation of healthy photoreceptor precursor cells into diseased murine eyes leads to the presence of functional photoreceptors within host retinae that express an array of donor-specific proteins. The resulting improvement in visual function was understood to be due to donor cells integrating within host retinae. Here, however, we show that while integration occurs the majority of donor-reporter-labelled cells in the host arises as a result of material transfer between donor and host photoreceptors. Material transfer does not involve permanent donor-host nuclear or cell-cell fusion, or the uptake of free protein or nucleic acid from the extracellular environment. Instead, RNA and/or protein are exchanged between donor and host cells in vivo. These data require a re-evaluation of the mechanisms underlying rescue by photoreceptor transplantation and raise the possibility of material transfer as a strategy for the treatment of retinal disorders.

The psychometric properties of the Quantitative-Checklist for Autism in Toddlers (Q-CHAT) as a measure of autistic traits in a community sample of Singaporean infants and toddlers.

BACKGROUND: There is growing research evidence that subclinical autistic traits are elevated in relatives of individuals with autism spectrum disorder (ASD), continuously distributed in the general population and likely to share common etiology with ASD. A number of measures have been developed to assess autistic traits quantitatively in unselected samples. So far, the Quantitative-Checklist for Autism in Toddlers (Q-CHAT) is one of very few measures developed for use with toddlers as young as 18 months, but little is known about its measurement properties and factor structure. METHODS: The present study examined internal consistency, factor structure, test-retest stability, and convergent validity of the Q-CHAT in a sample of toddlers in Singapore whose caregivers completed the Q-CHAT at 18 (n = 368) and 24 months (n = 396). RESULTS: Three factors were derived accounting for 38.1 % of the variance: social/communication traits, non-social/behavioral traits, and a speech/language factor. Internal consistency was suboptimal for the total and speech/language scores, but acceptable for the social/communication and non-social/behavioral factor scores. Scores were generally stable between 18 and 24 months. Convergent validity was found with the Pervasive Developmental Disorders subscale of the Child Behavior Checklist (CBCL) completed by caregivers when their children were 24 months. Q-CHAT total scores in this sample were higher than those reported in other unselected samples from the UK. CONCLUSIONS: The Q-CHAT was found to have a three-factor structure, acceptable internal consistency for its two main factor scores (social/communication and non-social/behavioral), normally distributed scores in an unselected sample, and similar structure and measurement properties as those reported in other published studies. Findings are discussed in relation to existing literature and future directions for the validation of the Q-CHAT.

Two consecutive partial liver transplants in a patient with Classic Maple Syrup Urine Disease.

Maple syrup urine disease is caused by a deficiency in the branched chain ketoacid dehydrogenase (BCKAD) complex. This results in the accumulation of branched chain amino acids (BCAA) and branched chain ketoacids in the body. Even when aggressively treated with dietary restriction of BCAA, patients experience long term cognitive, neurological and psychosocial problems. Liver transplantation from deceased donors has been shown to be an effective modality in introducing adequate BCKAD activity, attaining a metabolic cure for patients. Here, we report the clinical course of the first known patient with classic MSUD who received two consecutive partial liver grafts from two different living non-carrier donors and his five year outcome posttransplant. We also show that despite the failure of the first liver graft, and initial acute cellular rejection of the second liver graft in our patient, his metabolic control remained good without metabolic decompensation.

Inborn Error of Metabolism (IEM) screening in Singapore by electrospray ionization-tandem mass spectrometry (ESI/MS/MS): An 8 year journey from pilot to current program.

IEM screening by ESI/MS/MS was introduced in Singapore in 2006. There were two phases; a pilot study followed by implementation of the current program. The pilot study was over a 4 year period. During the pilot study, a total of 61,313 newborns were screened, and 20 cases of IEM were diagnosed (detection rate of 1:3065; positive predictive value (PPV) of 11%). Regular self-review, participation in external quality assessment and the Region 4 Genetic collaborative programs (http://www.region4genetics.org/) had led to the robust development of our current NBS MS/MS program. Overall, from July 2006 to April 2014, we screened a total of 177,267 newborns. The mean age at the time of sampling was 47.9h. Transportation of samples to the testing laboratory averaged 0.92 day. Upon receipt of sample, the NBS result was available within 1.64 days and within 3.8 days if a second tier test was required. Using absolute cut-off values in place of the initial 99th percentile reference range for the analyte markers and the introduction of two 2nd tier tests (MMA and Succinylacetone) had significantly reduced the high recall rate from an initial 1.5% during the period 2006-07 to 0.12% in 2013. The NBS MS/MS program was supported by a centralized confirmatory/diagnostic testing laboratory and a rapid response team of metabolic specialists. The detection rate was 1: 3165 (1:2727 if maternal conditions were also included). There were 23 newborns affected with organic acidemias (incidence: 1:6565), 23 with fatty acid oxidation disorders (incidence: 1:6565), and 10 with amino acidopathies (incidence 1:17,726). The performance metrics for the screening test were acceptable (sensitivity: 95.59%, specificity: 99.85%, PPV: 20%, FPR: 0.15). Participation in the NBS MS/MS program by hospitals was voluntary, and in 2013, the uptake rate was 71% of the annual births. We hope that newborn screening by MS/MS will become a standard of care for all babies in Singapore.

Differing courses of genetic evolution of Bradyrhizobium inoculants as revealed by long-term molecular tracing in Acacia mangium plantations.

Introducing nitrogen-fixing bacteria as an inoculum in association with legume crops is a common practice in agriculture. However, the question of the evolution of these introduced microorganisms remains crucial, both in terms of microbial ecology and agronomy. We explored this question by analyzing the genetic and symbiotic evolution of two Bradyrhizobium strains inoculated on Acacia mangium in Malaysia and Senegal 15 and 5 years, respectively, after their introduction. Based on typing of several loci, we showed that these two strains, although closely related and originally sampled in Australia, evolved differently. One strain was recovered in soil with the same five loci as the original isolate, whereas the symbiotic cluster of the other strain was detected with no trace of the three housekeeping genes of the original inoculum. Moreover, the nitrogen fixation efficiency was variable among these isolates (either recombinant or not), with significantly high, low, or similar efficiencies compared to the two original strains and no significant difference between recombinant and nonrecombinant isolates. These data suggested that 15 years after their introduction, nitrogen-fixing bacteria remain in the soil but that closely related inoculant strains may not evolve in the same way, either genetically or symbiotically. In a context of increasing agronomical use of microbial inoculants (for biological control, nitrogen fixation, or plant growth promotion), this result feeds the debate on the consequences associated with such practices.

International consensus on (ICON) pediatric asthma.

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.

Correction of severe thoracolumbar spondylolisthesis (grade 4) secondary to neurofibromatosis with posterior spinal instrumented fusion alone. A case report.

A 15-year-old teenager with Type 1 Neurofibromatosis presented with grade 4 spondylolisthesis over T12/L1 junction resulting paraparesis (Frankel D). Radiograph showed a Cobb angle of 88 degrees. Computed tomography scan showed dysplastic vertebral bodies, pedicles and facet joints of T11, T12 and L1 vertebra with complete T12/L1 facets dislocation. Magnetic resonance imaging confirmed presence of spinal cord compression. He underwent posterior instrumentation and posterolateral fusion (T8 to L4) using hybrid instrumentation. Extensive corticotomy of the posterior elements was followed by the use of large amount of bone graft. Post operatively, his neurology improved markedly back to normal. Radiographs showed a good correction of the deformity. He was immobilized in a thoracolumbar orthosis for six months. A solid posterior fusion was achieved at six months follow up. At 36-month follow up, he remained asymptomatic. This case report illustrates a successful treatment of a grade 4 thoracolumbar spondylolisthesis secondary to neurofibromatosis with posterior spinal fusion alone.

PlasmaKinetic™ (bipolar) transurethral resection of prostate: a prospective trial to study pathological artefacts, surgical parameters and clinical outcomes.

INTRODUCTION: The aims of the study were to compare the degree of cautery artefacts in prostatic chips between monopolar and PlasmaKinetic™ transurethral resection of prostate (TURP), and to determine if there is any difference in the intraoperative and post surgical parameters between them. METHODS: After institutional review board approval, patients were prospectively enrolled to undergo PlasmaKinetic™ TURP. Their parameters were compared with those of the historical monopolar TURP controls. All histological specimens were reviewed by a single senior pathologist. RESULTS: 46 patients were recruited to undergo PlasmaKinetic™ TURP. The resection time was significantly longer for the bipolar group compared to the monopolar group (50.2 versus 36.7 min, p-value is 0.001). The speed of resection (resection weight/time) was lower for the bipolar group (0.45 versus 0.56 g/min, p-value is 0.017). More irrigant was used for the bipolar group (21.2 versus 15.6 litres, p-value is 0.001) intraoperatively. There was no statistically significant difference in terms of intraoperative drop in haemoglobin and serum sodium change between the two groups. There seems to be a lesser degree of cautery artefacts in the PlasmaKinetic™ group than the monopolar group (42.17 versus 45.07 microns); however, this was not statistically significant (p-value is 0.452). CONCLUSION: Bipolar TURP seems to result in a lesser degree of cautery artefacts when compared to conventional monopolar TURP, albeit statistically insignificant, compared to monopolar TURP. TURP also resulted in a longer resection time and increased irrigant use, but no difference in blood loss and serum sodium levels.

Wide spectrum of filaggrin-null mutations in atopic dermatitis highlights differences between Singaporean Chinese and European populations.

BACKGROUND: Null mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris (IV) and predispose to atopic dermatitis (AD). Cohort studies in Europe and Japan have reported an FLG mutation carrier frequency of between 14% and 56%, but the prevalent European FLG mutations are rare or absent in Chinese patients with IV and AD. OBJECTIVES: To investigate further the spectrum of FLG-null mutations in Chinese patients and to compare it with that in other populations. METHODS: We conducted comprehensive FLG genetic analysis in a discovery cohort of 92 Singaporean Chinese individuals with IV and/or moderate-to-severe AD. All detected FLG mutations were then screened in a cohort of 425 patients with AD and 440 normal controls. Results In total, 22 FLG-null mutations, of which 14 are novel, were identified in this study; the combined null FLG genotype of 17 mutations detected in cases and controls showed strong association with AD [Fisher's exact test; P = 5·3 × 10⁻9; odds ratio (OR) 3·3], palmar hyperlinearity (Fisher's exact test; P = 9·0 × 10⁻¹5; OR 5·8), keratosis pilaris (Fisher's exact test; P = 0·001; OR 4·7) and with increased severity of AD (permutation test; P = 0·0063). CONCLUSIONS: This study emphasizes the wider genetic landscape of FLG-null mutations in Asia that is slowly emerging.

Insulin resistance is associated with a metabolic profile of altered protein metabolism in Chinese and Asian-Indian men.

AIMS/HYPOTHESIS: Insulin resistance (IR) is associated with obesity, but can also develop in individuals with normal body weight. We employed comprehensive profiling methods to identify metabolic events associated with IR, while controlling for obesity. METHODS: We selected 263 non-obese (BMI approximately 24 kg/m2) Asian-Indian and Chinese men from a large cross-sectional study carried out in Singapore. Individuals taking medication for diabetes or hyperlipidaemia were excluded. Participants were separated into lower and upper tertiles of IR based on HOMA indices of < or =1.06 or > or =1.93, respectively. MS-based metabolic profiling of acylcarnitines, amino acids and organic acids was combined with hormonal and cytokine profiling in all participants. RESULTS: After controlling for BMI, commonly accepted risk factors for IR, including circulating fatty acids and inflammatory cytokines, did not discriminate the upper and lower quartiles of insulin sensitivity in either Asian- Indian or Chinese men. Instead, IR was correlated with increased levels of alanine, proline, valine, leucine/isoleucine, phenylalanine, tyrosine, glutamate/glutamine and ornithine, and a cluster of branched-chain and related amino acids identified by principal components analysis. These changes were not due to increased protein intake by individuals in the upper quartile of IR. Increased abdominal adiposity and leptin, and decreased adiponectin and IGF-binding protein 1 were also correlated with IR. CONCLUSIONS/INTERPRETATION: These findings demonstrate that perturbations in amino acid homeostasis, but not inflammatory markers or NEFAs, are associated with IR in individuals of relatively low body mass.

An acoustical respiratory phase segmentation algorithm using genetic approach.

This paper proposes a robust and fully automated respiratory phase segmentation method using single channel tracheal breath sounds (TBS) recordings of different types. The estimated number of respiratory segments in a TBS signal is firstly obtained based on noise estimation and nonlinear mapping. Respiratory phase boundaries are then located through the generations of multi-population genetic algorithm by introducing a new evaluation function based on sample entropy (SampEn) and a heterogeneity measure. The performance of the proposed method is analyzed for single channel TBS recordings of various types. An overall respiratory phase segmentation accuracy is found to be 12 +/- 5 ms for normal TBS and 21 +/- 9 ms for adventitious sounds. The results show the robustness and effectiveness of the proposed segmentation method. The proposed method has been a successful attempt to solve the clinical application challenge faced by the existing phase segmentation methods in terms of respiratory dysfunctions.

A filter bank-based source extraction algorithm for heart sound removal in respiratory sounds.

In this paper, we consider the problem of heart sounds (HS) removal from respiratory sounds (RS), and a novel semi-blind single-channel source extraction algorithm is proposed. The proposed method is able to extract the underlying pure RS from the HS corrupted noisy input signals by incorporating the filter banks and template-based matching using FIR filters. For performance evaluation of the presented method, the average power spectral densities (PSD) of the input RS segments without HS have been compared with the PSD of the reconstructed signals over six selected frequency bands from 20 to 800Hz. The proposed method is tested for various types of RS recordings and found effective by yielding an overall maximum spectral difference of 2.8707+/-0.9875dB for a frequency range below 800Hz.

UGT1A1 haplotype mutation among Asians in Singapore.

BACKGROUND: The uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) enzyme is responsible for conjugation of the bilirubin in the liver as well as for drug metabolism. Some of the polymorphisms have been associated with an increased risk of neonatal hyperbilirubinemia which may explain the increased incidence of jaundice in an Asian population as well as exaggerated irinotecan-induced leukopenia. OBJECTIVE: The local Asian incidence of hypomorphic haplotypes, defined as gene mutations known to have a reduced function, has not been described. Clinical correlation between the mutations and the need for phototherapy for hyperbilirubinemia was carried out. METHODS: A cohort of 241 consecutive term infants delivered in the National University Hospital, Singapore, was recruited with parental consent. Cord blood was collected, and the promoter and coding regions of the UGT1A1 gene were sequenced. RESULTS: Six known haplotypes and 2 novel haplotypes were identified: 1 wild type, 5 with reduced function, while the 2 novel ones were predicted to have decreased function. The frequency of these hypomorphic haplotypes was high. Among the 241 infants screened, 35% had 1 hypomorphic haplotype and 12% had 2 hypomorphic haplotypes. The frequency was also different among ethnic groups, with 48% Chinese, 64% Indian and 31% Malay infants having at least 1 hypomorphic haplotype (chi(2) test, p < 0.05). There was a trend seen between the number of G71R mutations and the need for phototherapy (chi2 test for trend, p < 0.05). CONCLUSIONS: The local Asian incidence of hypomorphic haplotypes was high and there was a trend between the number of G71R mutations and the need for phototherapy. The G71R mutation may account for the increased incidence of neonatal jaundice seen in Asian populations.

Monitoring and treatment practices of childhood asthma in Singapore: a questionnaire study.

INTRODUCTION: Asthma is the most common chronic disease in children in Singapore. More than 20 percent of children will have been diagnosed with asthma by the age of 15 years. Most children are seen in the primary care setting, thus it is of value to study the management practices, especially of general practitioners, with comparison to gold standards. The aims of the study were to investigate: (a) Methods of monitoring asthma control; (b) Practices in managing acute exacerbations; and (c) Choice of therapy in maintenance treatment. METHODS: 2,100 questionnaires consisting of 35 questions were sent by post to general practitioners and various paediatric doctors throughout Singapore. 173 valid responses were received and results were compared to the 2006 Global Initiative for Asthma guidelines. RESULTS: 76.3 percent of respondents were general practitioners. 89.1 percent did not use symptom score cards / diaries. 37.6 percent did not use peak-flow meters / spirometers. 83.8 percent used a short-acting beta-agonist in acute exacerbations, but only 41.0 percent used oral corticosteroids in outpatients. A significant number used long-acting beta-agonists (LABA) in combination with inhaled steroids (29.5-41.6 percent) or as monotherapy (5.8-8.7 percent) for maintenance treatment. 91.3 percent never used immunotherapy in practice. CONCLUSION: Greater usage of diaries / score cards can be encouraged along with objective peak flow / spirometry measurements. Management of acute exacerbations is appropriate but corticosteroids are under-prescribed by most doctors. LABA continues to be prescribed for maintenance despite a lack of established safety profile for infants, along with recommendations that they only be used selectively in patients poorly-controlled by medium-dosage inhaled corticosteroids.

Unusually mild phenotype of AADC deficiency in 2 siblings.

Aromatic L-amino acid decarboxylase deficiency is a rare neurotransmitter defect leading to serotonin, dopamine and norepinephrine deficiency. Affected individuals usually present in infancy with severe developmental delay, oculogyric crises and extrapyramidal movements. We present the clinical, molecular and biochemical features of a pair of siblings who presented with fatigability, hypersomnolence and dystonia and who showed excellent response to treatment. Analysis of CSF biogenic amines, plasma AADC levels and direct sequencing of the DDC gene was performed. CSF catecholamine metabolites were reduced, with elevation of 3-O-methyldopa. Plasma AADC activity was undetectable in both siblings, and decreased in their carrier parents. One missense mutation (853C>T) was found in exon 8, and a donor splice site mutation was found in the intron after exon 6 (IVS6+4A>T). Both siblings showed excellent response to MAO inhibitor and dopamine agonist treatment. This report expands the clinical spectrum of AADC deficiency and contributes to the knowledge of the genotype and phenotype correlation for the DDC gene. It is important to recognize the milder phenotypes of the disease as these patients might respond well to therapy.