Combined mutations of NKX2-1 and surfactant protein C genes for refractory low oxyhemoglobin saturation and interstitial pneumonia: A case report.

RATIONALE: Mutations of the NKX2-1 gene are associated with brain-lung-thyroid syndrome, which is characterized by benign hereditary chorea, hypothyroidism, and pulmonary disease with variable presentation. Surfactant protein C (SFTPC) gene mutations result in chronic interstitial lung disease in adults or severe neonatal respiratory distress syndrome. PATIENT CONCERNS: Recurrent hypoxemia was observed shortly after birth in a baby at a gestational age of 40 weeks and birth weight of 3150 g. The need for respiratory support gradually increased. He had hypothyroidism and experienced feeding difficulties and irritability. DIAGNOSIS: Genetic examination of the peripheral blood revealed combined mutations of the NKX2-1 and SFTPC genes. INTERVENTIONS: The patient was administered respiratory support, antibiotics, low-dose dexamethasone, supplementary thyroxine, venous nutrition, and other supportive measures. OUTCOMES: The patient's guardian stopped treatment 3 months after commencement of treatment, due to the seriousness of his condition and the patient died. LESSONS: Combined mutations of NKX2-1 and SFTPC genes are very rare. Thus, idiopathic interstitial pneumonia with hypothyroidism and neurological disorders require special attention.

Choreoathetosis associated with non-chetotic hyperglycemia.

Choreoathetosis is a rare neurologic complication of the diabetic disease. The purpose of this case report is to increase the knowledge of such occurrence by describing the case of an elderly woman who was admitted to our institution for an over 20-day history of choreic movement in the left side of the body. She had a 6-year history of type 2 diabetes mellitus with a poor metabolic control including a glycosylated hemoglobin of 13%. Unenhanced computed tomography of the brain was negative. At magnetic resonance imaging, the right putamen showed high signal intensity on T1-weighted images and an area of high signal intensity on T2-weighted images, diffusion-weighted images and apparent diffusion coefficient maps. During the hospitalization, an adequate diet therapy was performed, and insulin therapy was gradually adjusted using regular insulin at main meals associated with basal insulin (glargine) "bed time". This resulted in progressive normalization of blood glucose values and an improvement of dyskinesia. There is a deep correlation between non-chetotic hyperglycemia and neurologic lesions leading to choreoathetosis. The etiopathogenesis seems multifactorial, and include hyperosmolar damage on cortical cells, alteration in GABA neurotransmission and in cerebral vascular self-regulation mechanism. Notably, in DM type 2 choreoathetosis may be related to both vascular and neuro-metabolic alterations in the basal nucleus due to inadequate glycemic control continuing in the time. This rare complication of DM type 2 is a pathological entity to be considered benign, since it is generally transient and reversible with the attainment of an adequate metabolic compensation.

A family with an atonic variant of paroxysmal kinesigenic choreoathetosis and hypercalcitoninemia.

We report a family with an incompletely atonic variant of paroxysmal kinesigenic choreoathetosis (PKC). Three members of the family experienced attacks of muscle weakness which resembled the choreoathetotic attacks that occur in PKC in terms of their kinesigenicity and duration, clarity of consciousness during the attacks, good therapeutic response to low doses of phenytoin, and familial transmission, but differed from choreoathetotic attacks in PKC in that they were atonic. All three affected individuals were hypercalcitoninemic.

[Paroxysmal dystonic choreoathetosis with chronic hemolytic anemia and morphologically abnormal erythrocytes].

A 38-year-old man was admitted to our hospital because of paroxysmal involuntary movement. He had a normal birth and normal development. No other members of his family had similar symptoms. He had attacks of choreoathetoic involuntary movement without loss of consciousness since about 11 years of age. Paroxysmal choreic movement occurred once or twice a month and lasted for 30 minutes to 4 hours. The attacks were intractable with phenytoin, phenobarbital, valproic acid, etc. He had slight disturbance of visual acuity due to toxoplasmosis and low intelligence (IQ 59, WAIS-R test). There were no other abnormal findings on general and neurological examinations. He was diagnosed as paroxysmal dystonic choreoathetosis (PDC) because of the typical attacks of paroxysmal choreic movement. He had macrocytic anemia with elliptocytes (13%) and stomatocytes (12%) but no acanthocytosis. There were increased reticulocytosis and low level of haptoglobin. Bone marrow aspiration showed increased erythroblasts. However, other hemolytic findings including bilirubin levels, Coombs test, osmolality tolerance test were normal. Biochemical analyses of erythrocyte membrane proteins and lipids, glycolytic enzymes activities and intermetabolites contents showed no abnormality. EEG revealed slow waves without abnormal paroxysmal discharges, and CT revealed no abnormal calcification. T2 weighted MRI showed bilateral multiple high intensity spots in the subcortical area, but no atrophy of the caudate nucleus. The pathogenesis of PDC is still unknown. In the present case, we suspect that a biochemical defect which had not been disclosed might result in abnormal erythrocyte membrane and PDC.

Chorea-acanthocytosis: a report of three new families and implications for genetic counselling.

Chorea-acanthocytosis (CHA) is a rare inherited neurologic disorder with peripheral red cell acanthocytes and normal serum lipoprotein levels. To date, 8 families with the disorder have been reported outside of Japan. We describe 4 patients in 3 families with CHA and review the clinical presentations in previous reports. In addition, we report magnetic resonance imaging scans in these patients. The pattern of inheritance in these families is most likely autosomal recessive. Obligate heterozygotes do not have acanthocytes on wet preparation under phase microscope. Two of 3 propositi were initially diagnosed as having Huntington chorea. Chorea-acanthocytosis is an important differential in the diagnosis of Huntington chorea and should be considered in families without a family history. The paucity of families with CHA reported to date may represent lack of recognition.

Copper clearance in a subgroup of patients with chorea.

Rat studies recently have suggested that the corpus striatum appears to be selectively and markedly affected by copper deficiencies beginning in the post-weanling period. A study of copper clearances has revealed that four out of five patients with chorea have depressed clearances between 0.00674 and .00313 (reference range 0.0137-0.0404 cc/min). The patients with depressed copper clearances had psychiatric illness themselves or in first-degree relatives. In the case of one patient, copper supplementation resulted in an abatement of symptoms that reversed on a single-blind crossover.

A pedigree of amyotrophic chorea with acanthocytosis.

Several pedigrees of which some members showed a clinical syndrome consisting of mental changes, choreatic involuntary movements, limb muscles atrophy, and acanthocytosis have been reported in the United States and the United Kingdom. Such a case and some of the family members who had such abnormalities as acanthocytosis, hypo-beta-lipoproteinemia, convulsions, and confusion was observed. Results of biochemical analysis of catecholamines and their metabolites in CSF and urine showed an elevated value of norepinephrine in CSF and increased urinary secretion of DOPAC. The authors propose to designate this syndrome an amyotrophic chorea with acanthocytosis.

Acute athetosis as a result of phenytoin toxicity in a child.

A case of acute athetosis in a child was found to be related to phenytoin toxicity. Symptoms were intermittent and coincided with drug administration. More common toxic effects were not noted on initial evaluation of the patient.