Clinical and genetic analysis of nonketotic hyperglycinemia:A case report

BACKGROUND Nonketotic hyperglycinemia(NKH)is a rare autosomal recessive genetic disorder of abnormal glycine metabolism caused by insufficient activity of the glycine cleavage enzyme system.Glycine is believed to function mainly as an inhibitory neurotransmitter,but it can also act as a co-agonist of the N-methyl-D-aspartate(NMDA)receptor.The accumulation of a large amount of glycine in the brain leads to neuronal and axonal injury via overactivation of NMDA receptors located in the hippocampus,cerebral cortex,olfactory bulb,and cerebellum and to stimulation of the inhibitory function of glycine receptors located in the spinal cord and brain stem,resulting in central apnea,hiccups,and hypotonia in the early stage of the disease.CASE SUMMARY The child described in this report had typical clinical manifestations of NKH,such as hiccups,disturbance of consciousness,hypotonia,and convulsions,within the first week after birth.Whole-exome genetic testing revealed that the child had a compound heterozygous mutation,namely,c.395C>A(p.S132X)and c.2182G>A(p.G728R),in the GLDC gene,and he was diagnosed with NKH.For treatment,we administered an oral levetiracetam solution and added topiramate and prednisone for epilepsy control,but the epilepsy remained uncontrollable.Ketogenic diet therapy was started at 6 mo of age,his seizures were significantly reduced,and there were no obvious adverse reactions during ketogenic treatment.Furthermore,we found that with the development of the disease,high levels of serum glycine decreased or even disappeared without intervention,and as the disease progressed,the corpus callosum became dysplastic.CONCLUSION This case shows that plasma glycine levels cannot be used to evaluate the prognosis of NKH,that the development of the corpus callosum can be affected by NKH,and that a ketogenic diet may be effective for seizure control in NKH patients.

Hemichorea in nonketotic hyperglycemia: Putamenal and cerebellum lesion on MR imaging

Hemichorea with corresponding putamenal T1 hyper-intensity and T2 hypointensity on MR imaging has occasionally been reported in diabetes mellitus with nonketotic hyperglycemia. However, the signal intensity in pu-tamenal and cerebellum lesion on MR imaging, which is believed to be pathogenetically related to hemichorea, is rarely documented in diabetes mellitus with nonketotic hyperglycemia. We describe a 57-year-old man with nonketotic hyperglycemic hemichorea on his right arm and legs, whose signal intensity in putamenal and cerebellum lesion was demonstrated by MR imaging.

Effect of acupuncture treatment on nonketotic hyperglycemic hemichorea-hemiballismus:a case report

Nonketotic hyperglycemic hemichorea-hemiballismus is a rare syndrome in the clinic,and treatment is often delayed.Hypoglycemic therapy is the most widely used and effective treatment,but some patients experience a slower improvement.Other symptomatic treatment medicines have some degree of side effects.Acupuncture treatment is beneficial for hemichoreahemiballismus.A male patient,aged 59 years,first visited our hospital outpatient department due to motor agitation with involuntary movements of the right limb.He had a history of type 2 diabetes mellitus and poor blood glucose control.His serum glucose was 26.5 mmol/L(normal:4.4-6.1 mmol/L),and magnetic resonance imaging demonstrated an irregular area of high signal intensity in T1-weighted imaging,low signal intensity on T2-weighted imaging,and high signal intensity in the left corpus striatum in T2-FLAIR imaging.Hospitalization was recommended for the patient.After ruling out other possibilities,he was eventually diagnosed with nonketotic hyperglycemic hemichorea-hemiballismus.Intensive glycemic control was immediately started with subcutaneous injection and acupuncture treatment at“governor vessel 13 acupoints”,and the involuntary movements completely disappeared on the ninth day of hospitalization.The pathophysiology of nonketotic hyperglycemic hemichorea-hemiballismus is unclear.Different patient histories lead to different brain tissue conditions,and relapses and uncontrolled blood glucose add difficulties to treatment.According to Traditional Chinese Medicine theory,insufficient kidney essence leads to brain dystrophy and causes the symptoms of hemichorea-hemiballismus.Research evidence has shown that acupuncture at"governor vessel 13 acupoints"has a beneficial treatment effect on nonketotic hyperglycemic hemichorea-hemiballismus.

Nonketotic hyperglycemia-related epileptic seizures

Objective:To investigate nonketotic hyperglycemia (NKH)-related epileptic clinical features and pathogenesis,and improve the diagnosis and treatment.Methods:Clinical data,including the clinical manifestations,laboratory tests,imaging studies and other information,of 13 patients with hyperglycemia-related epilepsy in our department were retrospectively analyzed.Results:Blood glucose levels of the 13 patients when admitted to the hospital ranged between 24.7-34.6 mmol/L (average 28.3 mmol/L),their plasma osmolality ranged between 290-332 mOsm/L (average 308 mOsm/L),and their ketone results were negative.Among them,seven had convulsions,4 had upper limbs and facial twitching,and 2 had bust twitch.Imaging findings could not detect accountable lesions related to seizures.EEG mainly showed spikes,slow waves,and scattered sharp slow waves.Insulin combined short-term antiepileptic drugs,allowed the epilepsy to be effectively controlled without recurrence.Interpretation:Patients with episodes of NKH epilepsy increased significantly with hyperglycemia.Raising awareness of the disease,early diagnosis,and very early lowering the hyperglycemia levels,can effectively control the seizures.Lowering blood glucose is an effective way to control blood glucose levels.

Hyperglycemic hemianopia:A case report

BACKGROUND Nonketotic hyperglycemia(NKH)is characterized by hyperglycemia with little or no ketoacidosis.Diverse neurological symptoms have been described in NKH patients,including choreoathetosis,hemiballismus,seizures,and coma in severe cases.Homonymous hemianopia,with or without occipital seizures,caused by hyperglycemia is less readily recognized.CASE SUMMARY We describe a 54-year-old man with NKH,who reported seeing round,colored flickering lights with right homonymous hemianopia.Cranial magnetic resonance imaging demonstrated abnormalities in the left occipital lobe,with decreased T2 signal of the white matter,restricted diffusion,and corresponding low signal intensity in the apparent diffusion coefficient map.He responded to rehydration and a low-dose insulin regimen,with improvements of his visual field defect.CONCLUSION Patients with NKH may present focal neurologic signs.Hyperglycemia should be taken into consideration when making an etiologic diagnosis of homonymous hemianopia.

Hemichorea Associated with Non-ketotic Hyperglycemia:A Case Report and Review of the Literature

Hemichorea associated with non-ketotic hyperglycemia(HC-NH)is a rare disease.The purpose of this case report is to introduce a patient with HC-NH and provide a schedule of examination and follow-up treatment.We also reviewed the current understanding of pathophysiology and treatment and how to apply it to our patients.The case involved a 37-year-old Asian diabetic man who had a 9-day history of losing movement in left limbs and face.His initial blood glucose level was 10.13 mmol/L.HbA1c was 13.6%.Before admission,head CT scan showed suspicious small pieces of left brainstem with slightly high-density shadow and right putamen nucleus with high-density shadow.On the day of admission,head MRI showed punctate T1WI low signal shadow,T2WI high and low mixed signal shadow,T1WI high signal shadow and T2WI low signal shadow of right putamen nucleus.The case findings were consistent with his displayed motor pattern and with the HC-NH diagnosis.Gradual control of the blood glucose levels alleviates his choreiform symptoms.The endocrinology follow-up 6 months after discharge found that his symptoms did not recur after the outpatient’s medication compliance was improved.HC-NH is a rare manifestation of poor diabetes control,but it should also be noticed by clinicians.Early recognition and gradual treatment of elevated blood glucose levels seem to completely alleviate choreiform symptoms.