[Clinical characteristics and prognosis of patients with anti-glutamic acid decarboxylase antibody-related cerebellar ataxia].

The clinical data, diagnosis, treatment, and prognosis of 10 patients with anti-glutamic acid decarboxylase (GAD) antibody-related cerebellar ataxia in Department of Neurology, Peking Union Medical College Hospital, from May 2015 to November 2021 were retrospectively analyzed. There were 8 female patients with a median age of 55 years old. Patients mainly presented with gait ataxia (10/10), dizziness (8/10), diplopia (6/10), and dysarthria (5/10). Four of them were complicated with other autoimmune disease, including vitiligo (3/4), Hashimoto thyroiditis (1/4), thrombocytopenia (1/4), and small cell lung cancer (1/4). All patients received immunotherapy, 6 out of 10 exhibited a good response, and half of them had satisfied functional prognosis. Patients of anti-GAD antibody-related cerebellar ataxia may be complicated with other autoimmune diseases, but underlying tumor is rare. More than half of patients have a good response to immunotherapy and satisfied prognosis.

[Neuropsychiatric symptoms and caregivers' distress in anti-N-methyl-D-aspartate receptor encephalitis].

Objective: To explore the characteristics of psychiatric symptoms and caregivers' distress in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Methods: Seventy-two patients with anti-NMDAR encephalitis were investigated in Peking Union Medical College Hospital from 2011 to 2018. The Chinese version of the Neuropsychiatric Inventory-Questionnaire (NPI-Q) was used to assess the severity of neuropsychiatric symptoms and caregivers' distress around the treatment. Results: A highly positive correlation existed between severity scores of neuropsychiatric symptoms and caregiver distress, and pre- and post-treatment correlation coefficients was 0.872 and 0.947, respectively (all P<0.001). The frequency of 12 symptom domains was higher than 45% before treatment, however, it significantly reduced to below 45% after treatment. Irritability/lability, agitation/aggression were the most common neuropsychiatric symptoms. Irritability/lability, agitation/aggression, and nighttime behavioral disturbances occurred concurrently. Patients with severe symptoms tended to be administrated antipsychotics (Z=-2.581, P=0.01). Neuropsychiatric symptoms significantly improved after immunotherapy (Z=-6.611, P<0.001). There was no significant difference in the symptom severity and distress subscale scores between the first episode and relapse around the therapy (P>0.05). Conclusion: Patients with anti NMDAR encephalitis often present severe neuropsychiatric symptoms, which aggravate the burden on caregivers. Immunotherapy significantly improves neuropsychiatric symptoms, and thus reduces the distress of caregivers.

[Clinical features of anti-myelin oligodendrocyte glycoprotein antibody-associated diseases in children with cortical encephalitis].

Objective: To describe the clinical features of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive cortical encephalitis in children. Methods: Patients who were hospitalized in Beijing Children's Hospital from June 2018 to October 2019, with positive MOG antibodies and phenotype of cortical encephalitis were retrospectively analyzed. Cell-based assays (CBAs) were used to test MOG antibodies. Results: Five patients had the phenotype of cortical encephalitis during follow-up, with 3 females and 2 males. The age of onset ranged from 8 years to 12 years and 1 month. At the last follow-up, 3 cases exhibited a monophasic course and 2 cases were with relapse and remission courses. Six out of 8 episodes which had the phenotype of cortical encephalitis presented with seizures, among which 3 episodes had status epilepticus. None had recurrent seizures during remission. Other symptoms included fever (7/8), headache and vomiting (4/8), somnolence (3/8) and hemiplegia (1/8). Unilateral cortical swelling was observed in cerebral magnetic resonance imaging (MRI) of all patients, without any hemorrhage and necrosis. White blood cell (WBC) counts of cerebrospinal fluid increased, ranging from8×10(6)/L to 186×10(6)/L. All patients recovered well after treatment with intravenous immunogloblin and glucocorticoid. Two patients had relapses during follow-up and were additionally treated with mycophenolate mofetil. Conclusions: Anti-MOG antibodies can induce cortical encephalitis. In clinical setting, fever, headache and seizures are common, however, severe consciousness disturbance and local neurological deficits are rare in these patients. Cerebral MRI shows unilateral cortical swelling without any hemorrhage and necrosis. Usually, immunotherapy works well. No patients exist repeated seizures in remission, but some patients may have relapses.

[Clinical featuers of adult patients with post-viral-encephalitis autoimmune encephalitis].

Objective: To explore the clinical features of post-viral-encephalitis autoimmune encephalitis (PVEAE). Methods: Ten cases of PVEAE, who were hospitalized in the Neurology Department of Peking Union Medical College Hospital (PUMCH) between November 2014 and October 2019, were retrospectively reviewed. Clinical manifestation, immunology, neuroradiology, treatment and outcomes were analyzed. Results: There were 5 males and 5 females, with a median age of 44 (18, 66) years. Of 9 cases, the median interval between the two onsets of encephalitis was 37 (24, 60) days, and there was no obvious interval in case 7. In viral encephalitis phase, the peak modified Rankin scale (mRS) was 4.5 (4.0, 5.0) and the remission mRS was 2.0 (1.0, 3.0). In autoimmune encephalitis (AE) phase, the peak mRS was 4.0 (3.0, 5.0). Symptoms of AE included mental and behavioral abnormalities (10/10), amnesia (10/10), motor disorders (5/10), autonomic dysfunction (5/10), speech disorders (4/10), seizures (2/10) and consciousness disturbance (2/10). On average, each case presented with 4 (2, 6) symptoms. In AE phase, the positive rate of anti-N-methyl-D-aspartate (anti-NMDA) receptor antibody in cerebrospinal fluid (CSF) was 80% (8/10), while in serum it was only 20% (2/10). Neuroimaging showed that in AE phase, the lesions expanded in 8 cases, remained unchanged in 1 case and shrank in 1 case. In AE phase, 10 cases received first line treatments, and 2 cases accepted long-course immunotherapy. After treatment, symptoms of 9 cases were obviously relieved. The mRS for short-term and long-term outcomes was 2.0 (1.0, 4.0) and 1.0 (0, 2.0), respectively. Conclusions: PVEAE might present with either typical biphasic course or monophasic/pseudo-monophasic course. In AE phase, anti-NMDA receptor antibody turned positive in most cases. Much importance should be attached to the recognition and diagnosis of PVEAE and treat it actively thereafter.

[Clinical approach and prognosis of continuous neurological care after intensive care for the patients with severe and refractory anti-N-methyl-D-aspartate receptor encephalitis].

Objective: To study the clinical features, continuous care and prognosis of the patients with severe and refractory anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis after intensive care unit (ICU). Methods: Clinical data of patients with severe and refractory anti-NMDAR encephalitis, who were transferred from ICU to general ward of neurology between December 2015 and October 2019, were retrospectively reviewed and analyzed in the study. Results: Twenty patients (11 females and 9 males) were enrolled in the study. The median course of disease when patients were transferred to general ward was 4.4 (2.0, 6.0) months. Six cases were alert, 6 cases were in a coma, 5 were in the early recovery phase and 3 were in the late recovery phase. Severe malnutrition, pneumonia, urinary tract infections, bedsores and leukocytopenia were common complications. Seven out of 18 patients were tested positive for cerebrospinal fluid anti-NMDAR antibodies with high titers (≥1∶100). During this continuous therapy stage,10 patients were treated with intravenous immunoglobulin (IVIg), 1 with methylprednisolone, 2 with rituximab, 1 with intrathecal methotrexate and 1 received intravenous cyclophosphamide. All Patients were prescribed a long-term immunotherapy (mycophenolate mofetil 1.5-3.0 g/d). Sixteen patients (80%) had good prognosis (modified Rankin Scale (mRS)≤2), and the mortality was 10%, with follow-up time of 17.0 (8.0, 27.0) months. Conclusions: Patients with anti-NMDAR encephalitis, who are transferred from ICU, have severely impaired neurologic function. These patients need long-term individualized immunotherapy and continuous neurological care. Good outcomes can be achieved in most patients.

[Clinical experience and next-generation sequencing analysis of encephalitis caused by pseudorabies virus].

Objective: To detect potential pathogens including pseudorabies virus in patients with encephalitis of unknown etiology in China and describe novel encephalitic entities. Methods: Patients with clinically suspected infectious encephalitis were enrolled in a multicenter study to identify the pathogens in PUMCH Encephalitis Program.Next-generation sequencing(NGS) of cerebrospinal fluid (CSF) was used in patients with encephalitis of unknown etiology enrolled from 2016 to 2017.The patients diagnosed as PRV encephalitis were studied to describe this novel entity. Results: The four patients(3 male, 1 male, 38-54 years old) had occupational exposure to raw park when working in the production or marketing of pork and at least one got injured during pork-cutting.Two of them were confirmed with NGS of CSF, and anti-PRV antibodies were positive in 3 patients whose serum was available for serological analysis.They all presented with an acute onset of fever, convulsion, loss of consciousness and respiratory failure within 1 to 4 days and rapidly deteriorated even on extensive treatment.All the patients needed ICU admission and 3 needed mechanical ventilation.Two patients also had bilateral retinitis.Neuroimaging revealed symmetric gray matter lesions including limbic system, basal ganglia and midbrain without obvious hemorrhage.Lumbar puncture revealed elevated intracranial pressure and lymphocytic pleocytosis [(6-64)×10(6)/L] of CSF.The patients failed to response to the treatment of acyclovir combined with intravenous immunoglobulin and steroids.Modified Rankin Score was 3, 5, 5 and 6 (died) for the 4 patients respectively on last follow-up. Conclusions: PRV could be a cause of severe encephalitis.The patients with suspected pseudorabies encephalitis (PRE) need to be tested for PRV DNA timely.Severe encephalitis with bilateral involvement of limbic system, basal ganglion, thalamus and midbrain in patient with occupational exposure indicate this emerging infectious encephalitis.

[A clinical analysis of 20 patients with neurobrucellosis].

Objective: To investigate the epidemiological and clinical features of 20 patients with neurobrucellosis (NB) . Methods: The epidemiological, clinical, laboratory and treatment data of patients diagnosed with NB from 2010 to 2016 in Peking Union Medical College Hospital were retrospectively analyzed. Results: Twelve (60%) patients reported the history of contact with infected animals and intake of raw milk product. The common manifestations included headache (85%, 17/20), fatigue (85%, 17/20), fever (80%, 16/20), weight loss (70%, 15/20), the signs included pathological reflection (70%, 15/20), decreased muscle strength(45%, 9/20). The mean time to diagnosis was 7.9 months. All patients were diagnosed by positive serum antibody against Brucella. Body fluid culture revealed positive blood Brucella in 5 (31.2%, 5/16) patients and positive cerebrospinal fluid in 3 (16.7%, 3/18) patients. The medication consisted of rifampicin and minocycline based regimens or combined with ceftriaxone, fluroquinolone, streptomycin or trimethoprim-sulfamethoxazole (TMP-SMX). Ninety percent(18/20) patients obtained clinical improvement, whereas mild sequelae were observed in 5 patients. Conclusions: Clinical features of NB are heterogeneous. Carefully seek for epidemiological clues and early tests for Brucella may lead to well outcome. Combination therapy with two or more active antimicrobial agents is suggested.

[Clinical analysis of paraneoplastic neurological syndrome associated with thymoma].

Objectives: To investigate the clinical features, diagnosis and treatment of antibody mediated paraneoplastic neurological syndrome associated with thymoma. Methods: From 2012 to 2017, the paraneoplastic antibody and neuron antibody were tested from both blood and cerebrospinal fluid (CSF) in consecutive patients clinically suspected with neurological paraneoplastic syndromes/unknown encephalitis in Peking Union Medical College Hospital.The clinical data, lab results, electrophysiological examinations, imaging features, treatment and clinical prognosis were collected.In this study, the patients who met the diagnostic criteria of both thymoma and neurological paraneoplastic syndrome were retrospectively analyzed.The functional severity was assessed by modified Rankin score(mRS). Results: Six patients (4 female and 2 male) were included for the analysis.Of them, 4 patients presented with limbic encephalitis, 1 with peripheral neuropathy accompanying with myasthenia gravis and 1 with spinal and cerebella degeneration.Three patients were in severe condition (mRS=5). Positive α-amino-3-hydroxy-5-methyl-4-iso xazolepropionic acid receptor, antibody (AMPAR) was identified in 3 patients(2 in blood and CSF, 1 in blood), CV2 plus acetylcholine receptor antibody (ACH-Ab) positive in blood was seen in 1 patient and positive N-methyl-D-aspartate receptor (NMDAR) in blood and CSF in 1 patient. Brain MRI showed abnormalities in 2 patients.The CT scan revealed thymoma in all 6 patients.All patients received intravenous immunogloblin (IVIG) and/or glucocorticoid immediately after diagnosis.Furthermore, thymectomy was performed in 5 patients. All the patients were remarkably improved with mRS 0-1 at discharge.Five patients were clinical stable within follow-up of 1-2.5 years.However, one patient who refused thymectomy experienced several clinical recurrencs. Conclusions: Antibodies mediated paraneoplastic neurological syndrome/autoimmune encephalitis can occur in patients with thymoma with typical characteristics. The correlated antibody test and chest CT might be important in patients clinically suspected with neurological paraneoplastic syndrome or encephalitis with unknown reason. Surgical thymectomy combining with active immunological treatment may play a role in the favorable prognosis, even in those clinical severe patients.

[Analysis of prodromal phase and prodromal events in anti-N-methyl-D-aspartate receptor encephalitis].

Objective: To analyze prodromal phase and prodromal events of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Methods: Clinical data of 179 patients hospitalized and diagnosed during 2010-2016 including adults and children in Peking Union Medical College Hospital and Beijing Children's Hospital were collected.Patients with prodromal phase or prodromal events were selected.A retrospective analysis of clinical characteristics including prodromal phase or prodromal events, course of disease, brain imaging, laboratory results and therapeutic effect was performed. Results: Prodromal phase was presented in 31.8% (57/179) of patients.Most common symptoms included fever (73.7%) and headache (68.4%). Prodromal phase was prolonged in 6 patients, the longest being 64 days.Among those 6 patients (10.5%), headache and fever were the only symptoms throughout disease courses in 3 cases.Prodromal events were reported in 6.1% (11/179) of patients, including 5 patients after HSV1 encephalitis, 1 after Japanese encephalitis, and 2 after resection of melanocytic nevi. Conclusions: Anti-NMDAR encephalitis can be preceded with prolonged prodromal phase.In some patients prodromal symptoms are the only clinical presentation.Clinical features of those atypical cases suggest that infection may be the precipitating factor.Viral encephalitis including HSV1 encephalitis and Japanese encephalitis may be prodromal events in some cases.

[Immunotherapy strategy for 35 cases of severe anti-N-methyl-D-aspartate receptor encephalitis].

OBJECTIVE: To provide evidence for establishing standardized treatment strategy of severe anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in China, by demonstrating the clinical characteristics and comparing the treatment strategy with that adopted in foreign countries. METHODS: A total of 35 hospitalized cases who met the diagnostic criteria for severe anti-NMDAR encephalitis were retrospectively analyzed. Demographic data, clinical history, past medical history, laboratory tests, imaging studies, treatment and the follow-up information were recorded using unified forms. RESULTS: Mental and behavioral abnormalities, seizures and consciousness disturbance occurred in all cases; involuntary movements, speech disorders, memory loss, central hypoventilation and autonomic dysfunction happened in 45%-65% of cases. Sixteen patients (45.71%) required mechanical ventilation. Modified Rankin score (mRS ) arranged 4-5 (mean mRS 4.86). The percentage of patients with elevated intracranial pressure, white blood cell and protein in cerebrospinal fluid were 42.86%, 60.00%, and 14.29%, respectively. Abnormal findings in brain magnetic resonance imaging scan happened in 31.43% cases, located in frontal lobe, temporal lobe, insular lobe, hippocampus, cingulate gyrus, corpus callosum, brain stem, and cerebellum. All cases received intravenous immunoglobulin, for one to maximum seven cycles, with an average of three cycles. 91.43% of cases received glucocorticoid therapy, including 54.29% of cases received high-dose methylprednisolone. Two patients (5.71%) received plasma exchange. Five patients(14.29%) received second-line therapy including rituximab for 4 patients and intravenous cyclophosphamide (CTX) for one. Fifteen patients(42.86%) received long-term immunosuppression therapy. All cases acquired improvement after immunotherapy and were transferred out from ICU, the median ICU time was 46 days and median hospitalized duration was 72 days. The mRS were 5 for 2 cases, 1-4 for the rest patients, and no patient died during hospitalization. During a median follow-up period of 17.6 months, 30 of 35 patients (85.71%) achieved complete recovery or a good outcome (mRS 0-2). Eleven patients (31.43%) relapsed. One patient(2.90%) died 2 years after discharge. CONCLUSION: Intravenous immunoglobulin combined with high-dose methylprednisolone therapy is effective for severe anti-NMDAR encephalitis. Retrial of the first-line immunotherapy is an option for initially unresponsive cases.

[Pediatric autoimmune encephalitis associated with anti-glutamic acid decarboxylase 65 antibody: two cases report and literature review].

Objective: To investigate the clinical features and prognosis of pediatric autoimmune encephalitis associated with anti-glutamic acid decarboxylase 65 (GAD65) antibody. Methods: Clinical data of 2 patients diagnosed as autoimmune encephalitis associated with anti-GAD65 antibody at Department of Neurology, Beijing Children's Hospital in 2019 were analyzed retrospectively. A literature search with "anti-GAD65 antibody""encephalitis""epilepsy" or "cerebellar ataxia" as key words was conducted at China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform and PubMed (up to January 2020). The clinical features and prognosis of pediatric cases with complete clinical data were retrieved and summarized. Results: Two patients with positive anti-GAD65 antibody of serum and cerebrospinal fluid were both females. The onset age of case 1 was 57 months and her main clinical manifestations were fever and unconsciousness. The cranial magnetic resonance imaging (MRI) showed diffuse T2 weighted imaging (T2WI) abnormal signals, and the electroencephalogram (EEG) showed slow waves. The onset age of case 2 was 80 months and her main clinical manifestations of were recurrent focal seizures, memory loss, and headache. The MRI showed high T2WI signal in bilateral hippocampus, and the EEG showed abnormal discharge involving the temporal area. Both cases were treated with methylprednisolone and intravenous immunoglobulin, the short-term symptoms of them were both improved. They were followed up for 6 months and 1 year respectively, the case 1 recovered completely, and the case 2 still had focal seizures. Six English reports which included 6 cases were retrieved. Together with these 2 cases, a total of 8 cases were analyzed. The clinical symptoms included seizures (6 cases), memory loss (4 cases), loss of consciousness (3 cases), behavioral abnormalities (3 cases), cognitive impairment (2 cases), headache (2 cases), autonomic symptoms (1 case), ataxia (1 case), dysphagia (1 case), and aphasia (1 case). There were 5 cases with cranial MRI abnormalities in the acute phase or sub-acute phase, of whom 3 cases had the limbic system involvement, and 2 cases were mainly had extra limbic area involvement. Three cases had hippocampal atrophy or sclerosis during follow-up. All 8 patients were treated with immunotherapy. After immunotherapy, all patients had short-term improvement. Follow-up for 6 months to 6 years showed that 3 cases with extra limbic encephalitis improved to baseline levels, and 5 limbic encephalitis cases had poor outcomes, including 1 death and 4 cases still had focal epilepsy. Conclusions: Pediatric anti-GAD65 antibody associated autoimmune encephalitis is a rare but treatable disease, including limbic encephalitis and extra limbic encephalitis. The most common clinical manifestations are seizures and memory impairment. Early diagnosis and immunotherapy can improve the symptoms in a short time. But patients with limbic encephalitis often had refractory epilepsy in the chronic phase, and have a poor long-term outcome.

[Clinical observation on the overlapping syndrome of myelin oligodendrocyte glycoprotein antibody and anti-N-methyl-D aspartate receptor in children].

Objective: To investigate the clinical features, imaging findings and prognosis of children with overlapping syndrome of myelin oligodendrocyte glycoprotein (MOG) antibody disease and anti-N-methyl-D aspartate receptor (NMDAR) encephalitis (MNOS). Methods: The clinical manifestations, immunological antibodies in blood and cerebrospinal fluid, cranial image, treatment and follow-up of 11 patients diagnosed as MNOS in the Department of Neurology, Beijing Children's Hospital from January 2011 to April 2019 were analyzed retrospectively. Results: A total of 11 patients, including 4 males and 7 females were analyzed, the age of onset was (10.4±2.3) years. A total of 29 episodes occurred in 11 children. At the last follow-up, 8 cases showed relapsed remission course, the interval of recurrence was 3 to 60 months. The onset symptoms of 11 patients included convulsions (10 cases), lethargy (6 cases), psychosis (6 cases). Among 29 episodes, the common symptoms were convulsions (16 episodes), psychosis (13 episodes),and lethargy (10 episodes). According to the diagnostic criteria of anti-NMDAR encephalitis and MOG-antibody disease, 29 episodes were divided into three phenotypes, including anti-NMDAR encephalitis(4 episodes), MOG-antibody diseases (10 episodes) and overlapping types (15 episodes).Twenty-seven times of acute stage cranial magnetic resonance imaging (MRI) were available, common lesions included cortical focus (22 times), subcortical white matter (7 times), brainstem (9 times). All patients were sensitive to first-line immunotherapy. Eight patients had recurrence during glucocorticoid reduction, 6 of them were treated with additional second-line immunosuppressive therapy, including cyclophosphamide (1 case) and mycophenolate mofetil (5 cases). The follow-up time of patients were 5-99 months. At the last follow-up, all patients were in remission, the pediatric cerebral performance category (PCPC) score was 1 (10 cases) and 2 (1 cases). Conclusions: MNOS mainly affects older children. In the period of acute episodes, convulsions and psychosis are common. The cranial MRI showed extensive brain involvement and mainly in the cortex. The recurrence rates of MNOS are relatively high, patients are sensitive to first-line immunotherapy. No significant neurological dysfunction was left in the remission stage.

[Clinical characteristics and next generation sequencing of three cases of Listeria monocytogenes meningitis with complications].

Objective: To summarize the clinical characteristics of Listeria monocytogenes meningitis (LMM) with complications, and analyze the outcomes of next generation sequencing. Methods: Clinical characteristics, laboratory findings, imaging features, antibiotics treatment, and next generation sequencing of cerebrospinal fluid were analyzed in 3 LMM patients who were hospitalized in the Department of Infectious Diseases of Beijing Children's Hospital Affiliated to Capital Medical University from July 2015 to November 2017. Results: The three patients were 1-year-old girl, 2-year-old girl, and 9-year-old boy, with normal immune function. They had eaten refrigerated food, milk or dairy products before onset. Symptoms included fever, headache, abdominal pain, diarrhea, vomiting, and convulsions, etc. The complications of two cases (case 2 and 3) were appendicitis and Meckel's diverticulitis. The other one (case 1) was with sepsis and pneumonia. Leukocyte counts in cerebrospinal fluid were elevated in all the three cases, and cranial magnetic resonance imaging showed meningeal or periventricular involvement. All the children were diagnosed with LMM by positive CSF culture. CSF for next generation sequencing was sent after carbapenem antibiotics using, yet all the results were positive. The positive results were returned 2, 9, and 9 days earlier than culture results, respectively. The gene coverage was 5.00%, 7.00%, 0.04%, and the reads was 2 561, 1 011 and 8, respectively. All the three children had recurrent fever despite using cephalosporin. Levels of leukocytes in the blood and CSF further elevated. After using carbapenem antibiotics, patients improved eventually and were discharged from hospital. Conclusions: LMM can occur in children with normal immune function and is usually associated with digestive system symptoms. Listeria monocytogenes can be detected quickly and accurately by the next generation sequencing technology, without being limited to sampling time and antibiotics application.

[Clinical diagnosis and treatment of three cases with hyperornithinemia-hyperammonemia-homocitrullinuria syndrome].

Objective: To study the clinical characteristics, methods of diagnosis and treatment of hyperornithinemia-hyperammonemia- homocitrullinuria (HHH) syndrome. Method: From July 2011 to August 2016, 3 Chinese patients with HHH syndrome were enrolled in this study. The clinical course, biochemical features, brain MRI findings, and gene mutations were analyzed. Result: The three patients' age at onset of symptoms was 3 months to 7 years, and the age of diagonosis was 3 years and 10 months to 9 years and 10 months. All of them presented with intolerance to protein-rich foods from the infant period, development retardation and abnormal posture. Case 1 and 2 had moderate mental retardation. Serum ammonia 25-276 µmol/L (reference range<60 µmol/L), alanine aminotransferase (ALT) 20-139 IU/L (reference range 9-50 IU/L), ornithine 29.12-99.44 µmol/L(reference range 15-100 µmol/L), urinary orotic acid 1.49-29.75 mmol/mol Cr (reference range 0-7 mmol/mol Cr), uracil 6.09-103.97 mmol/mol Cr (reference range 0-1.5 mmol/mol Cr). The cranial MRI revealed lesions in the basal ganglia, abnormal white matter signal, progressive demyelination and cerebral atrophy. On their SLC25A15 gene, a novel homozygous missense mutation c. 416A>G (p.E139G) was identified in case 1, a known pathogenic homozygous nonsense mutation c. 535C>T was found in case 2 and 3. Liver transplantation had been performed when case 1 was 6 years old. Significant improvements were observed in dietary habit, mental and motor functions, and biochemical parameters. After the dietary intervention with the supplements of arginine, L-carnitine, case 2 was improved, spastic paraplegia of case 3 had no mitigation. Liver transplant was recommended. Conclusion: HHH syndrome has an aversion to protein-rich food, and the patients have recurrent vomiting and progressive neurological dysfunction. Clinical diagnosis of HHH syndrome is difficult and patients may present with incomplete biochemical phenotype. The genetic analysis is key for the diagnosis. Depending on their condition, individuals with HHH syndrome can be treated with a low-protein diet, drugs and liver transplantation.